@article{DedukhDaCruzKneitzetal.2022, author = {Dedukh, Dmitrij and Da Cruz, Irene and Kneitz, Susanne and Marta, Anatolie and Ormanns, Jenny and Tichop{\´a}d, Tom{\´a}š and Lu, Yuan and Alsheimer, Manfred and Janko, Karel and Schartl, Manfred}, title = {Achiasmatic meiosis in the unisexual Amazon molly, Poecilia formosa}, series = {Chromosome Research}, volume = {30}, journal = {Chromosome Research}, number = {4}, doi = {10.1007/s10577-022-09708-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325128}, pages = {443-457}, year = {2022}, abstract = {Unisexual reproduction, which generates clonal offspring, is an alternative strategy to sexual breeding and occurs even in vertebrates. A wide range of non-sexual reproductive modes have been described, and one of the least understood questions is how such pathways emerged and how they mechanistically proceed. The Amazon molly, Poecilia formosa, needs sperm from males of related species to trigger the parthenogenetic development of diploid eggs. However, the mechanism, of how the unreduced female gametes are produced, remains unclear. Cytological analyses revealed that the chromosomes of primary oocytes initiate pachytene but do not proceed to bivalent formation and meiotic crossovers. Comparing ovary transcriptomes of P. formosa and its sexual parental species revealed expression levels of meiosis-specific genes deviating from P. mexicana but not from P. latipinna. Furthermore, several meiosis genes show biased expression towards one of the two alleles from the parental genomes. We infer from our data that in the Amazon molly diploid oocytes are generated by apomixis due to a failure in the synapsis of homologous chromosomes. The fact that this failure is not reflected in the differential expression of known meiosis genes suggests the underlying molecular mechanism may be dysregulation on the protein level or misexpression of a so far unknown meiosis gene, and/or hybrid dysgenesis because of compromised interaction of proteins from diverged genomes.}, language = {en} } @article{FofanovProkopovKuhletal.2020, author = {Fofanov, Mikhail V. and Prokopov, Dmitry Yu. and Kuhl, Heiner and Schartl, Manfred and Trifonov, Vladimir A.}, title = {Evolution of microRNA biogenesis genes in the sterlet (Acipenser ruthenus) and other polyploid vertebrates}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {24}, issn = {1422-0067}, doi = {10.3390/ijms21249562}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285230}, year = {2020}, abstract = {MicroRNAs play a crucial role in eukaryotic gene regulation. For a long time, only little was known about microRNA-based gene regulatory mechanisms in polyploid animal genomes due to difficulties of polyploid genome assembly. However, in recent years, several polyploid genomes of fish, amphibian, and even invertebrate species have been sequenced and assembled. Here we investigated several key microRNA-associated genes in the recently sequenced sterlet (Acipenser ruthenus) genome, whose lineage has undergone a whole genome duplication around 180 MYA. We show that two paralogs of drosha, dgcr8, xpo1, and xpo5 as well as most ago genes have been retained after the acipenserid-specific whole genome duplication, while ago1 and ago3 genes have lost one paralog. While most diploid vertebrates possess only a single copy of dicer1, we strikingly found four paralogs of this gene in the sterlet genome, derived from a tandem segmental duplication that occurred prior to the last whole genome duplication. ago1,3,4 and exportins1,5 look to be prone to additional segment duplications producing up to four-five paralog copies in ray-finned fishes. We demonstrate for the first time exon microsatellite amplification in the acipenserid drosha2 gene, resulting in a highly variable protein product, which may indicate sub- or neofunctionalization. Paralogous copies of most microRNA metabolism genes exhibit different expression profiles in various tissues and remain functional despite the rediploidization process. Subfunctionalization of microRNA processing gene paralogs may be beneficial for different pathways of microRNA metabolism. Genetic variability of microRNA processing genes may represent a substrate for natural selection, and, by increasing genetic plasticity, could facilitate adaptations to changing environments.}, language = {en} } @article{NandaSchoriesSimeonovetal.2022, author = {Nanda, Indrajit and Schories, Susanne and Simeonov, Ivan and Adolfi, Mateus Contar and Du, Kang and Steinlein, Claus and Alsheimer, Manfred and Haaf, Thomas and Schartl, Manfred}, title = {Evolution of the degenerated Y-chromosome of the swamp guppy, Micropoecilia picta}, series = {Cells}, volume = {11}, journal = {Cells}, number = {7}, issn = {2073-4409}, doi = {10.3390/cells11071118}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267242}, year = {2022}, abstract = {The conspicuous colour sexual dimorphism of guppies has made them paradigmatic study objects for sex-linked traits and sex chromosome evolution. Both the X- and Y-chromosomes of the common guppy (Poecilia reticulata) are genetically active and homomorphic, with a large homologous part and a small sex specific region. This feature is considered to emulate the initial stage of sex chromosome evolution. A similar situation has been documented in the related Endler's and Oropuche guppies (P. wingei, P. obscura) indicating a common origin of the Y in this group. A recent molecular study in the swamp guppy (Micropoecilia. picta) reported a low SNP density on the Y, indicating Y-chromosome deterioration. We performed a series of cytological studies on M. picta to show that the Y-chromosome is quite small compared to the X and has accumulated a high content of heterochromatin. Furthermore, the Y-chromosome stands out in displaying CpG clusters around the centromeric region. These cytological findings evidently illustrate that the Y-chromosome in M. picta is indeed highly degenerated. Immunostaining for SYCP3 and MLH1 in pachytene meiocytes revealed that a substantial part of the Y remains associated with the X. A specific MLH1 hotspot site was persistently marked at the distal end of the associated XY structure. These results unveil a landmark of a recombining pseudoautosomal region on the otherwise strongly degenerated Y chromosome of M. picta. Hormone treatments of females revealed that, unexpectedly, no sexually antagonistic color gene is Y-linked in M. picta. All these differences to the Poecilia group of guppies indicate that the trajectories associated with the evolution of sex chromosomes are not in parallel.}, language = {en} } @article{BiltuevaProkopovRomanenkoetal.2020, author = {Biltueva, Larisa S. and Prokopov, Dmitry Yu. and Romanenko, Svetlana A. and Interesova, Elena A. and Schartl, Manfred and Trifonov, Vladimir A.}, title = {Chromosome distribution of highly conserved tandemly arranged repetitive DNAs in the Siberian sturgeon (Acipenser baerii)}, series = {Genes}, volume = {11}, journal = {Genes}, number = {11}, issn = {2073-4425}, doi = {10.3390/genes11111375}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219371}, year = {2020}, abstract = {Polyploid genomes present a challenge for cytogenetic and genomic studies, due to the high number of similar size chromosomes and the simultaneous presence of hardly distinguishable paralogous elements. The karyotype of the Siberian sturgeon (Acipenser baerii) contains around 250 chromosomes and is remarkable for the presence of paralogs from two rounds of whole-genome duplications (WGD). In this study, we applied the sterlet-derived acipenserid satDNA-based whole chromosome-specific probes to analyze the Siberian sturgeon karyotype. We demonstrate that the last genome duplication event in the Siberian sturgeon was accompanied by the simultaneous expansion of several repetitive DNA families. Some of the repetitive probes serve as good cytogenetic markers distinguishing paralogous chromosomes and detecting ancestral syntenic regions, which underwent fusions and fissions. The tendency of minisatellite specificity for chromosome size groups previously observed in the sterlet genome is also visible in the Siberian sturgeon. We provide an initial physical chromosome map of the Siberian sturgeon genome supported by molecular markers. The application of these data will facilitate genomic studies in other recent polyploid sturgeon species.}, language = {en} } @article{AdolfiDuKneitzetal.2021, author = {Adolfi, Mateus C. and Du, Kang and Kneitz, Susanne and Cabau, C{\´e}dric and Zahm, Margot and Klopp, Christophe and Feron, Romain and Paix{\~a}o, R{\^o}mulo V. and Varela, Eduardo S. and de Almeida, Fernanda L. and de Oliveira, Marcos A. and N{\´o}brega, Rafael H. and Lopez-Roques, C{\´e}line and Iampietro, Carole and Lluch, J{\´e}r{\^o}me and Kloas, Werner and Wuertz, Sven and Schaefer, Fabian and St{\"o}ck, Matthias and Guiguen, Yann and Schartl, Manfred}, title = {A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas)}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-01066-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265672}, year = {2021}, abstract = {Arapaima gigas is one of the largest freshwater fish species of high ecological and economic importance. Overfishing and habitat destruction are severe threats to the remaining wild populations. By incorporating a chromosomal Hi-C contact map, we improved the arapaima genome assembly to chromosome-level, revealing an unexpected high degree of chromosome rearrangements during evolution of the bonytongues (Osteoglossiformes). Combining this new assembly with pool-sequencing of male and female genomes, we identified id2bbY, a duplicated copy of the inhibitor of DNA binding 2b (id2b) gene on the Y chromosome as candidate male sex-determining gene. A PCR-test for id2bbY was developed, demonstrating that this gene is a reliable male-specific marker for genotyping. Expression analyses showed that this gene is expressed in juvenile male gonads. Its paralog, id2ba, exhibits a male-biased expression in immature gonads. Transcriptome analyses and protein structure predictions confirm id2bbY as a prime candidate for the master sex-determiner. Acting through the TGF beta signaling pathway, id2bbY from arapaima would provide the first evidence for a link of this family of transcriptional regulators to sex determination. Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes.}, language = {en} } @article{HelmprobstKneitzKlotzetal.2021, author = {Helmprobst, Frederik and Kneitz, Susanne and Klotz, Barbara and Naville, Magali and Dechaud, Corentin and Volff, Jean-Nicolas and Schartl, Manfred}, title = {Differential expression of transposable elements in the medaka melanoma model}, series = {PLoS One}, volume = {16}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0251713}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260615}, year = {2021}, abstract = {Malignant melanoma incidence is rising worldwide. Its treatment in an advanced state is difficult, and the prognosis of this severe disease is still very poor. One major source of these difficulties is the high rate of metastasis and increased genomic instability leading to a high mutation rate and the development of resistance against therapeutic approaches. Here we investigate as one source of genomic instability the contribution of activation of transposable elements (TEs) within the tumor. We used the well-established medaka melanoma model and RNA-sequencing to investigate the differential expression of TEs in wildtype and transgenic fish carrying melanoma. We constructed a medaka-specific TE sequence library and identified TE sequences that were specifically upregulated in tumors. Validation by qRT- PCR confirmed a specific upregulation of a LINE and an LTR element in malignant melanomas of transgenic fish.}, language = {en} } @article{HojsgaardSchartl2021, author = {Hojsgaard, Diego and Schartl, Manfred}, title = {Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules}, series = {BioEssays}, volume = {43}, journal = {BioEssays}, number = {1}, doi = {10.1002/bies.202000111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225818}, year = {2021}, abstract = {The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.}, language = {en} } @article{AdolfiHerpinMartinezBengocheaetal.2021, author = {Adolfi, Mateus C. and Herpin, Amaury and Martinez-Bengochea, Anabel and Kneitz, Susanne and Regensburger, Martina and Grunwald, David J. and Schartl, Manfred}, title = {Crosstalk Between Retinoic Acid and Sex-Related Genes Controls Germ Cell Fate and Gametogenesis in Medaka}, series = {Frontiers in Cell and Developmental Biology}, volume = {8}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2020.613497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222669}, year = {2021}, abstract = {Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1-/-adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.}, language = {en} } @article{BiscottiCarducciBaruccaetal.2020, author = {Biscotti, Maria Assunta and Carducci, Federica and Barucca, Marco and Gerdol, Marco and Pallavicini, Alberto and Schartl, Manfred and Canapa, Adriana and Contar Adolfi, Mateus}, title = {The transcriptome of the newt Cynops orientalis provides new insights into evolution and function of sexual gene networks in sarcopterygians}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-62408-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227326}, year = {2020}, abstract = {Amphibians evolved in the Devonian period about 400 Mya and represent a transition step in tetrapod evolution. Among amphibians, high-throughput sequencing data are very limited for Caudata, due to their largest genome sizes among terrestrial vertebrates. In this paper we present the transcriptome from the fire bellied newt Cynops orientalis. Data here presented display a high level of completeness, comparable to the fully sequenced genomes available from other amphibians. Moreover, this work focused on genes involved in gametogenesis and sexual development. Surprisingly, the gsdf gene was identified for the first time in a tetrapod species, so far known only from bony fish and basal sarcopterygians. Our analysis failed to isolate fgf24 and foxl3, supporting the possible loss of both genes in the common ancestor of Rhipidistians. In Cynops, the expression analysis of genes described to be sex-related in vertebrates singled out an expected functional role for some genes, while others displayed an unforeseen behavior, confirming the high variability of the sex-related pathway in vertebrates.}, language = {en} } @article{AnelliOrdasKneitzetal.2018, author = {Anelli, Viviana and Ordas, Anita and Kneitz, Susanne and Sagredo, Leonel Munoz and Gourain, Victor and Schartl, Manfred and Meijer, Annemarie H. and Mione, Marina}, title = {Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression}, series = {Frontiers in Genetics}, volume = {9}, journal = {Frontiers in Genetics}, number = {675}, issn = {1664-8021}, doi = {10.3389/fgene.2018.00675}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196963}, year = {2018}, abstract = {Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression. The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc\&acc=GSE37015.}, language = {en} } @article{BertChmielewskaBergmannetal.2016, author = {Bert, Bettina and Chmielewska, Justyna and Bergmann, Sven and Busch, Maximilian and Driever, Wolfgang and Finger-Baier, Karin and H{\"o}ßler, Johanna and K{\"o}hler, Almut and Leich, Nora and Misgeld, Thomas and N{\"o}ldner, Torsten and Reiher, Annegret and Schartl, Manfred and Seebach-Sproedt, Anja and Thumberger, Thomas and Sch{\"o}nfelder, Gilbert and Grune, Barbara}, title = {Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish}, series = {The EMBO Journal}, volume = {35}, journal = {The EMBO Journal}, number = {11}, doi = {10.15252/embj.201694448}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188783}, pages = {1151-1154}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{DechaudVolffSchartletal.2019, author = {Dechaud, Corentin and Volff, Jean-Nicolas and Schartl, Manfred and Naville, Magali}, title = {Sex and the TEs: transposable elements in sexual development and function in animals}, series = {Mobile DNA}, volume = {10}, journal = {Mobile DNA}, doi = {10.1186/s13100-019-0185-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202510}, pages = {42}, year = {2019}, abstract = {Transposable elements are endogenous DNA sequences able to integrate into and multiply within genomes. They constitute a major source of genetic innovations, as they can not only rearrange genomes but also spread ready-to-use regulatory sequences able to modify host gene expression, and even can give birth to new host genes. As their evolutionary success depends on their vertical transmission, transposable elements are intrinsically linked to reproduction. In organisms with sexual reproduction, this implies that transposable elements have to manifest their transpositional activity in germ cells or their progenitors. The control of sexual development and function can be very versatile, and several studies have demonstrated the implication of transposable elements in the evolution of sex. In this review, we report the functional and evolutionary relationships between transposable elements and sexual reproduction in animals. In particular, we highlight how transposable elements can influence expression of sexual development genes, and how, reciprocally, they are tightly controlled in gonads. We also review how transposable elements contribute to the organization, expression and evolution of sexual development genes and sex chromosomes. This underscores the intricate co-evolution between host functions and transposable elements, which regularly shift from a parasitic to a domesticated status useful to the host.}, language = {en} } @article{SchartlKneitzVolkoffetal.2019, author = {Schartl, Manfred and Kneitz, Susanne and Volkoff, Helene and Adolfi, Mateus and Schmidt, Cornelia and Fischer, Petra and Minx, Patrick and Tomlinson, Chad and Meyer, Axel and Warren, Wesley C.}, title = {The piranha genome provides molecular insight associated to its unique feeding behavior}, series = {Genome Biology and Evolution}, volume = {11}, journal = {Genome Biology and Evolution}, number = {8}, doi = {10.1093/gbe/evz139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202218}, pages = {2099-2106}, year = {2019}, abstract = {The piranha enjoys notoriety due to its infamous predatory behavior but much is still not understood about its evolutionary origins and the underlying molecular mechanisms for its unusual feeding biology. We sequenced and assembled the red-bellied piranha (Pygocentrus nattereri) genome to aid future phenotypic and genetic investigations. The assembled draft genome is similar to other related fishes in repeat composition and gene count. Our evaluation of genes under positive selection suggests candidates for adaptations of piranhas' feeding behavior in neural functions, behavior, and regulation of energy metabolism. In the fasted brain, we find genes differentially expressed that are involved in lipid metabolism and appetite regulation as well as genes that may control the aggression/boldness behavior of hungry piranhas. Our first analysis of the piranha genome offers new insight and resources for the study of piranha biology and for feeding motivation and starvation in other organisms.}, language = {en} } @article{DuWuertzAdolfietal.2019, author = {Du, Kang and Wuertz, Sven and Adolfi, Mateus and Kneitz, Susanne and St{\"o}ck, Matthias and Oliveira, Marcos and N{\´o}brega, Rafael and Ormanns, Jenny and Kloas, Werner and Feron, Romain and Klopp, Christophe and Parrinello, Hugues and Journot, Laurent and He, Shunping and Postlethwait, John and Meyer, Axel and Guiguen, Yann and Schartl, Manfred}, title = {The genome of the arapaima (Arapaima gigas) provides insights into gigantism, fast growth and chromosomal sex determination system}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-41457-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201333}, pages = {5293}, year = {2019}, abstract = {We have sequenced the genome of the largest freshwater fish species of the world, the arapaima. Analysis of gene family dynamics and signatures of positive selection identified genes involved in the specific adaptations and unique features of this iconic species, in particular it's large size and fast growth. Genome sequences from both sexes combined with RAD-tag analyses from other males and females led to the isolation of male-specific scaffolds and supports an XY sex determination system in arapaima. Whole transcriptome sequencing showed that the product of the gland-like secretory organ on the head surface of males and females may not only provide nutritional fluid for sex-unbiased parental care, but that the organ itself has a more specific function in males, which engage more in parental care.}, language = {en} } @article{MatosMachadoSchartletal.2019, author = {Matos, Isa and Machado, Miguel P. and Schartl, Manfred and Coelho, Maria Manuela}, title = {Allele-specific expression variation at different ploidy levels in Squalius alburnoides}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-40210-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200910}, pages = {3688}, year = {2019}, abstract = {Allopolyploid plants are long known to be subject to a homoeolog expression bias of varying degree. The same phenomenon was only much later suspected to occur also in animals based on studies of single selected genes in an allopolyploid vertebrate, the Iberian fish Squalius alburnoides. Consequently, this species became a good model for understanding the evolution of gene expression regulation in polyploid vertebrates. Here, we analyzed for the first time genome-wide allele-specific expression data from diploid and triploid hybrids of S. alburnoides and compared homoeolog expression profiles of adult livers and of juveniles. Co-expression of alleles from both parental genomic types was observed for the majority of genes, but with marked homoeolog expression bias, suggesting homoeolog specific reshaping of expression level patterns in hybrids. Complete silencing of one allele was also observed irrespective of ploidy level, but not transcriptome wide as previously speculated. Instead, it was found only in a restricted number of genes, particularly ones with functions related to mitochondria and ribosomes. This leads us to hypothesize that allelic silencing may be a way to overcome intergenomic gene expression interaction conflicts, and that homoeolog expression bias may be an important mechanism in the achievement of sustainable genomic interactions, mandatory to the success of allopolyploid systems, as in S. alburnoides.}, language = {en} } @article{LiuKinoshitaAdolfietal.2019, author = {Liu, Ruiqi and Kinoshita, Masato and Adolfi, Mateus C. and Schartl, Manfred}, title = {Analysis of the role of the Mc4r system in development, growth, and puberty of medaka}, series = {Frontiers in Endocrinology}, volume = {10}, journal = {Frontiers in Endocrinology}, doi = {10.3389/fendo.2019.00213}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201472}, pages = {213}, year = {2019}, abstract = {In mammals the melanocortin 4 receptor (Mc4r) signaling system has been mainly associated with the regulation of appetite and energy homeostasis. In fish of the genus Xiphophorus (platyfish and swordtails) puberty onset is genetically determined by a single locus, which encodes the mc4r. Wild populations of Xiphophorus are polymorphic for early and late-maturing individuals. Copy number variation of different mc4r alleles is responsible for the difference in puberty onset. To answer whether this is a special adaptation of the Mc4r signaling system in the lineage of Xiphophorus or a more widely conserved mechanism in teleosts, we studied the role of Mc4r in reproductive biology of medaka (Oryzias latipes), a close relative to Xiphophorus and a well-established model to study gonadal development. To understand the potential role of Mc4r in medaka, we characterized the major features of the Mc4r signaling system (mc4r, mrap2, pomc, agrp1). In medaka, all these genes are expressed before hatching. In adults, they are mainly expressed in the brain. The transcript of the receptor accessory protein mrap2 co-localizes with mc4r in the hypothalamus in adult brains indicating a conserved function of modulating Mc4r signaling. Comparing growth and puberty between wild-type and mc4r knockout medaka revealed that absence of Mc4r does not change puberty timing but significantly delays hatching. Embryonic development of knockout animals is retarded compared to wild-types. In conclusion, the Mc4r system in medaka is involved in regulation of growth rather than puberty.}, language = {en} } @article{JonesFrucianoKelleretal.2016, author = {Jones, Julia C. and Fruciano, Carmelo and Keller, Anja and Schartl, Manfred and Meyer, Axel}, title = {Evolution of the elaborate male intromittent organ of Xiphophorus fishes}, series = {Ecology and Evolution}, volume = {6}, journal = {Ecology and Evolution}, number = {20}, doi = {10.1002/ece3.2396}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164956}, pages = {7207-7220}, year = {2016}, abstract = {Internally fertilizing animals show a remarkable diversity in male genital morphology that is associated with sexual selection, and these traits are thought to be evolving particularly rapidly. Male fish in some internally fertilizing species have "gonopodia," highly modified anal fins that are putatively important for sexual selection. However, our understanding of the evolution of genital diversity remains incomplete. Contrary to the prediction that male genital traits evolve more rapidly than other traits, here we show that gonopodial traits and other nongonopodial traits exhibit similar evolutionary rates of trait change and also follow similar evolutionary models in an iconic genus of poeciliid fish (Xiphophorus spp.). Furthermore, we find that both mating and nonmating natural selection mechanisms are unlikely to be driving the diverse Xiphophorus gonopodial morphology. Putative holdfast features of the male genital organ do not appear to be influenced by water flow, a candidate selective force in aquatic habitats. Additionally, interspecific divergence in gonopodial morphology is not significantly higher between sympatric species, than between allopatric species, suggesting that male genitals have not undergone reproductive character displacement. Slower rates of evolution in gonopodial traits compared with a subset of putatively sexually selected nongenital traits suggest that different selection mechanisms may be acting on the different trait types. Further investigations of this elaborate trait are imperative to determine whether it is ultimately an important driver of speciation.}, language = {en} } @article{MateosKangKloppetal.2019, author = {Mateos, Mariana and Kang, Du and Klopp, Christophe and Parrinello, Hugues and Garc{\´i}a-Olaz{\´a}bal, Mateo and Schumer, Molly and Jue, Nathaniel K. and Guiguen, Yann and Schartl, Manfred}, title = {Draft genome assembly and annotation of the Gila Topminnow Poeciliopsis occidentalis}, series = {Frontiers in Ecology and Evolution}, volume = {7}, journal = {Frontiers in Ecology and Evolution}, number = {404}, issn = {2296-701X}, doi = {10.3389/fevo.2019.00404}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190339}, year = {2019}, abstract = {No abstract available.}, language = {en} } @article{ShenChalopinGarciaetal.2016, author = {Shen, Yingjia and Chalopin, Domitille and Garcia, Tzintzuni and Boswell, Mikki and Boswell, William and Shiryev, Sergey A. and Agarwala, Richa and Volff, Jean-Nicolas and Postlethwait, John H. and Schartl, Manfred and Minx, Patrick and Warren, Wesley C. and Walter, Ronald B.}, title = {X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, doi = {10.1186/s12864-015-2361-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164582}, pages = {37}, year = {2016}, abstract = {Background Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85 years. Use of various interspecies hybrids to investigate the genetics underlying spontaneous and induced tumorigenesis has resulted in the development and maintenance of pedigreed Xiphophorus lines specifically bred for research. The recent availability of the X. maculatus reference genome assembly now provides unprecedented opportunities for novel and exciting comparative research studies among Xiphophorus species. Results We present sequencing, assembly and annotation of two new genomes representing Xiphophorus couchianus and Xiphophorus hellerii. The final X. couchianus and X. hellerii assemblies have total sizes of 708 Mb and 734 Mb and correspond to 98 \% and 102 \% of the X. maculatus Jp 163 A genome size, respectively. The rates of single nucleotide change range from 1 per 52 bp to 1 per 69 bp among the three genomes and the impact of putatively damaging variants are presented. In addition, a survey of transposable elements allowed us to deduce an ancestral TE landscape, uncovered potential active TEs and document a recent burst of TEs during evolution of this genus. Conclusions Two new Xiphophorus genomes and their corresponding transcriptomes were efficiently assembled, the former using a novel guided assembly approach. Three assembled genome sequences within this single vertebrate order of new world live-bearing fishes will accelerate our understanding of relationship between environmental adaptation and genome evolution. In addition, these genome resources provide capability to determine allele specific gene regulation among interspecies hybrids produced by crossing any of the three species that are known to produce progeny predisposed to tumor development.}, language = {en} } @article{LiuChenGaoetal.2017, author = {Liu, Han and Chen, Chunhai and Gao, Zexia and Min, Jiumeng and Gu, Yongming and Jian, Jianbo and Jiang, Xiewu and Cai, Huimin and Ebersberger, Ingo and Xu, Meng and Zhang, Xinhui and Chen, Jianwei and Luo, Wei and Chen, Boxiang and Chen, Junhui and Liu, Hong and Li, Jiang and Lai, Ruifang and Bai, Mingzhou and Wei, Jin and Yi, Shaokui and Wang, Huanling and Cao, Xiaojuan and Zhou, Xiaoyun and Zhao, Yuhua and Wei, Kaijian and Yang, Ruibin and Liu, Bingnan and Zhao, Shancen and Fang, Xiaodong and Schartl, Manfred and Qian, Xueqiao and Wang, Weimin}, title = {The draft genome of blunt snout bream (Megalobrama amblycephala) reveals the development of intermuscular bone and adaptation to herbivorous diet}, series = {GigaScience}, volume = {6}, journal = {GigaScience}, number = {7}, doi = {10.1093/gigascience/gix039}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170844}, year = {2017}, abstract = {The blunt snout bream Megalobrama amblycephala is the economically most important cyprinid fish species. As an herbivore, it can be grown by eco-friendly and resource-conserving aquaculture. However, the large number of intermuscular bones in the trunk musculature is adverse to fish meat processing and consumption. As a first towards optimizing this aquatic livestock, we present a 1.116-Gb draft genome of M. amblycephala, with 779.54 Mb anchored on 24 linkage groups. Integrating spatiotemporal transcriptome analyses, we show that intermuscular bone is formed in the more basal teleosts by intramembranous ossification and may be involved in muscle contractibility and coordinating cellular events. Comparative analysis revealed that olfactory receptor genes, especially of the beta type, underwent an extensive expansion in herbivorous cyprinids, whereas the gene for the umami receptor T1R1 was specifically lost in M. amblycephala. The composition of gut microflora, which contributes to the herbivorous adaptation of M. amblycephala, was found to be similar to that of other herbivores. As a valuable resource for the improvement of M. amblycephala livestock, the draft genome sequence offers new insights into the development of intermuscular bone and herbivorous adaptation.}, language = {en} } @article{BiscottiGerdolCanapaetal.2016, author = {Biscotti, Maria Assunta and Gerdol, Marco and Canapa, Adriana and Forconi, Mariko and Olmo, Ettore and Pallavicini, Alberto and Barucca, Marco and Schartl, Manfred}, title = {The Lungfish Transcriptome: A Glimpse into Molecular Evolution Events at the Transition from Water to Land}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {21571}, doi = {10.1038/srep21571}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167753}, year = {2016}, abstract = {Lungfish and coelacanths are the only living sarcopterygian fish. The phylogenetic relationship of lungfish to the last common ancestor of tetrapods and their close morphological similarity to their fossil ancestors make this species uniquely interesting. However their genome size, the largest among vertebrates, is hampering the generation of a whole genome sequence. To provide a partial solution to the problem, a high-coverage lungfish reference transcriptome was generated and assembled. The present findings indicate that lungfish, not coelacanths, are the closest relatives to land-adapted vertebrates. Whereas protein-coding genes evolve at a very slow rate, possibly reflecting a "living fossil" status, transposable elements appear to be active and show high diversity, suggesting a role for them in the remarkable expansion of the lungfish genome. Analyses of single genes and gene families documented changes connected to the water to land transition and demonstrated the value of the lungfish reference transcriptome for comparative studies of vertebrate evolution.}, language = {en} } @article{WagnerFischerThomaetal.2011, author = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred}, title = {CrossQuery: A Web Tool for Easy Associative Querying of Transcriptome Data}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0028990}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134787}, pages = {e28990}, year = {2011}, abstract = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deep-sequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.}, language = {en} } @article{BiscottiAdolfiBaruccaetal.2018, author = {Biscotti, Maria Assunta and Adolfi, Mateus Contar and Barucca, Marco and Forconi, Mariko and Pallavicini, Alberto and Gerdol, Marco and Canapa, Adriana and Schartl, Manfred}, title = {A comparative view on sex differentiation and gametogenesis genes in lungfish and coelacanths}, series = {Genome Biology and Evolution}, volume = {10}, journal = {Genome Biology and Evolution}, number = {6}, doi = {10.1093/gbe/evy101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176774}, pages = {1430-1444}, year = {2018}, abstract = {Gonadal sex differentiation and reproduction are the keys to the perpetuation of favorable gene combinations and positively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as "living fossils" and as the direct ancestors of tetrapods. Here, we report for the first time the characterization of >50 genes related to sex differentiation and gametogenesis in Latimeria menadoensis and Protopterus annectens. Although the expression profiles of most genes is consistent with the intermediate position of basal sarcopterygians between actinopterygian fish and tetrapods, their phylogenetic placement and presence/absence patterns often reveal a closer affinity to the tetrapod orthologs. On the other hand, particular genes, for example, the male gonad factor gsdf (Gonadal Soma-Derived Factor), provide examples of ancestral traits shared with actinopterygians, which disappeared in the tetrapod lineage.}, language = {en} } @article{KottlerSchartl2018, author = {Kottler, Verena A. and Schartl, Manfred}, title = {The colorful sex chromosomes of teleost fish}, series = {Genes}, volume = {9}, journal = {Genes}, number = {5}, doi = {10.3390/genes9050233}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176587}, pages = {233}, year = {2018}, abstract = {Teleost fish provide some of the most intriguing examples of sexually dimorphic coloration, which is often advantageous for only one of the sexes. Mapping studies demonstrated that the genetic loci underlying such color patterns are frequently in tight linkage to the sex-determining locus of a species, ensuring sex-specific expression of the corresponding trait. Several genes affecting color synthesis and pigment cell development have been previously described, but the color loci on the sex chromosomes have mostly remained elusive as yet. Here, we summarize the current knowledge about the genetics of such color loci in teleosts, mainly from studies on poeciliids and cichlids. Further studies on these color loci will certainly provide important insights into the evolution of sex chromosomes.}, language = {en} } @article{MatosSucenaMachadoetal.2011, author = {Matos, Isa and Sucena, {\`E}lio and Machado, Miguel P and Gardner, Rui and In{\´a}cio, {\^A}ngela and Schartl, Manfred and Coelho, Maria M}, title = {Ploidy mosaicism and allele-specific gene expression differences in the allopolyploid \(Squalius\) \(alburnoides\)}, series = {BMC Genetics}, volume = {12}, journal = {BMC Genetics}, number = {101}, doi = {10.1186/1471-2156-12-101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142879}, pages = {1-10}, year = {2011}, abstract = {Background Squalius alburnoides is an Iberian cyprinid fish resulting from an interspecific hybridisation between Squalius pyrenaicus females (P genome) and males of an unknown Anaecypris hispanica- like species (A genome). S. alburnoides is an allopolyploid hybridogenetic complex, which makes it a likely candidate for ploidy mosaicism occurrence, and is also an interesting model to address questions about gene expression regulation and genomic interactions. Indeed, it was previously suggested that in S. alburnoides triploids (PAA composition) silencing of one of the three alleles (mainly of the P allele) occurs. However, not a whole haplome is inactivated but a more or less random inactivation of alleles varying between individuals and even between organs of the same fish was seen. In this work we intended to correlate expression differences between individuals and/or between organs to the occurrence of mosaicism, evaluating if mosaics could explain previous observations and its impact on the assessment of gene expression patterns. Results To achieve our goal, we developed flow cytometry and cell sorting protocols for this system generating more homogenous cellular and transcriptional samples. With this set-up we detected 10\% ploidy mosaicism within the S. alburnoides complex, and determined the allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin) in cells from liver and kidney of mosaic and non-mosaic individuals coming from different rivers over a wide geographic range. Conclusions Ploidy mosaicism occurs sporadically within the S. alburnoides complex, but in a frequency significantly higher than reported for other organisms. Moreover, we could exclude the influence of this phenomenon on the detection of variable allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin) in cells from liver and kidney of triploid individuals. Finally, we determined that the expression patterns previously detected only in a narrow geographic range is not a local restricted phenomenon but is pervasive in rivers where S. pyrenaicus is sympatric with S. alburnoides. We discuss mechanisms that could lead to the formation of mosaic S. alburnoides and hypothesise about a relaxation of the mechanisms that impose a tight control over mitosis and ploidy control in mixoploids."}, language = {en} } @article{SchartlSchoriesWatamatsuetal.2018, author = {Schartl, Manfred and Schories, Susanne and Watamatsu, Yuko and Nagao, Yusuke and Hashimoto, Hisashi and Bertin, Chlo{\´e} and Mourot, Brigitte and Schmidt, Cornelia and Wilhelm, Dagmar and Centanin, Lazaro and Guiguen, Yann and Herpin, Amaury}, title = {Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements}, series = {BMC Biology}, volume = {16}, journal = {BMC Biology}, number = {16}, doi = {10.1186/s12915-018-0485-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175827}, year = {2018}, abstract = {Background: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination. Results: We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal. Conclusions: Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element.}, language = {en} } @article{SchartlShenMaurusetal.2015, author = {Schartl, Manfred and Shen, Yingjia and Maurus, Katja and Walter, Ron and Tomlinson, Chad and Wilson, Richard K. and Postlethwait, John and Warren, Wesley C.}, title = {Whole body melanoma transcriptome response in medaka}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0143057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144714}, pages = {e0143057}, year = {2015}, abstract = {The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.}, language = {en} } @article{KangManousakiFranchinietal.2015, author = {Kang, Ji Hyoun and Manousaki, Tereza and Franchini, Paolo and Kneitz, Susanne and Schartl, Manfred and Meyer, Axel}, title = {Transcriptomics of two evolutionary novelties: how to make a sperm-transfer organ out of an anal fin and a sexually selected "sword" out of a caudal fin}, series = {Ecology and Evolution}, volume = {5}, journal = {Ecology and Evolution}, number = {4}, doi = {10.1002/ece3.1390}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144139}, pages = {848-864}, year = {2015}, abstract = {Swords are exaggerated male ornaments of swordtail fishes that have been of great interest to evolutionary biologists ever since Darwin described them in the Descent of Man (1871). They are a novel sexually selected trait derived from modified ventral caudal fin rays and are only found in the genus Xiphophorus. Another phylogenetically more widespread and older male trait is the gonopodium, an intromittent organ found in all poeciliid fishes, that is derived from a modified anal fin. Despite many evolutionary and behavioral studies on both traits, little is known so far about the molecular mechanisms underlying their development. By investigating transcriptomic changes (utilizing a RNA-Seq approach) in response to testosterone treatment in the swordtail fish, Xiphophorus hellerii, we aimed to better understand the architecture of the gene regulatory networks underpinning the development of these two evolutionary novelties. Large numbers of genes with tissue-specific expression patterns were identified. Among the sword genes those involved in embryonic organ development, sexual character development and coloration were highly expressed, while in the gonopodium rather more morphogenesis-related genes were found. Interestingly, many genes and genetic pathways are shared between both developing novel traits derived from median fins: the sword and the gonopodium. Our analyses show that a larger set of gene networks was co-opted during the development and evolution of the older gonopodium than in the younger, and morphologically less complex trait, the sword. We provide a catalog of candidate genes for future efforts to dissect the development of those sexually selected exaggerated male traits in swordtails.}, language = {en} } @article{LamatschAdolfssonSenioretal.2015, author = {Lamatsch, Dunja K. and Adolfsson, Sofia and Senior, Alistair M. and Christiansen, Guntram and Pichler, Maria and Ozaki, Yuichi and Smeds, Linnea and Schartl, Manfred and Nakagawa, Shinichi}, title = {A transcriptome derived female-specific marker from the invasive Western mosquitofish (Gambusia affinis)}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0118214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144004}, pages = {e0118214}, year = {2015}, abstract = {Sex-specific markers are a prerequisite for understanding reproductive biology, genetic factors involved in sex differences, mechanisms of sex determination, and ultimately the evolution of sex chromosomes. The Western mosquitofish, Gambusia affinis, may be considered a model species for sex-chromosome evolution, as it displays female heterogamety (ZW/ZZ), and is also ecologically interesting as a worldwide invasive species. Here, de novo RNA-sequencing on the gonads of sexually mature G. affinis was used to identify contigs that were highly transcribed in females but not in males (i.e., transcripts with ovary-specific expression). Subsequently, 129 primer pairs spanning 79 contigs were tested by PCR to identify sex-specific transcripts. Of those primer pairs, one female-specific DNA marker was identified, Sanger sequenced and subsequently validated in 115 fish. Sequence analyses revealed a high similarity between the identified sex-specific marker and the 3' UTR of the aminomethyl transferase (amt) gene of the closely related platyfish (Xiphophorus maculatus). This is the first time that RNA-seq has been used to successfully characterize a sex-specific marker in a fish species in the absence of a genome map. Additionally, the identified sex-specific marker represents one of only a handful of such markers in fishes.}, language = {en} } @article{AdolfiHerpinRegensburgeretal.2016, author = {Adolfi, Mateus C. and Herpin, Amaury and Regensburger, Martina and Sacquegno, Jacopo and Waxman, Joshua S. and Schartl, Manfred}, title = {Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, doi = {10.1038/srep34281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147843}, pages = {34281}, year = {2016}, abstract = {In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.}, language = {en} } @article{BrunetVolffSchartl2016, author = {Brunet, Fr{\´e}d{\´e}ric G. and Volff, Jean-Nicolas and Schartl, Manfred}, title = {Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates}, series = {Genome Biology Evolution}, volume = {8}, journal = {Genome Biology Evolution}, number = {15}, doi = {10.1093/gbe/evw103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146988}, pages = {1600-1613}, year = {2016}, abstract = {The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75\% after 1R/2R, 64.4\% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.}, language = {en} } @article{KneitzMishraChalopinetal.2016, author = {Kneitz, Susanne and Mishra, Rasmi R. and Chalopin, Domitille and Postlethwait, John and Warren, Wesley C. and Walther, Ronald B. and Schartl, Manfred}, title = {Germ cell and tumor associated piRNAs in the medaka and \(Xiphophorus\) melanoma models}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, number = {357}, doi = {10.1186/s12864-016-2697-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146028}, year = {2016}, abstract = {Background A growing number of studies report an abnormal expression of Piwi-interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution. However, little is known about piRNAs in somatic and neoplastic tissues of fish. Results To identify piRNA clusters that might be involved in melanoma pathogenesis, we use several transgenic lines of medaka, and platyfish/swordtail hybrids, which develop various types of melanoma. In these tumors Piwi, is expressed at different levels, depending on tumor type. To quantify piRNA levels, whole piRNA populations of testes and melanomas of different histotypes were sequenced. Because no reference piRNA cluster set for medaka or Xiphophorus was yet available we developed a software pipeline to detect piRNA clusters in our samples and clusters were selected that were enriched in one or more samples. We found several loci to be overexpressed or down-regulated in different melanoma subtypes as compared to hyperpigmented skin. Furthermore, cluster analysis revealed a clear distinction between testes, low-grade and high-grade malignant melanoma in medaka. Conclusions Our data imply that dysregulation of piRNA expression may be associated with development of melanoma. Our results also reinforce the importance of fish as a suitable model system to study the role of piRNAs in tumorigenesis.}, language = {en} } @article{SchulSchmittRegnerietal.2013, author = {Schul, Daniela and Schmitt, Alexandra and Regneri, Janine and Schartl, Manfred and Wagner, Toni Ulrich}, title = {Bursted BMP Triggered Receptor Kinase Activity Drives Smad1 Mediated Long-Term Target Gene Oscillation in c2c12 Cells}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0059442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130131}, pages = {e59442}, year = {2013}, abstract = {Bone Morphogenetic Proteins (BMPs) are important growth factors that regulate many cellular processes. During embryogenesis they act as morphogens and play a critical role during organ development. They influence cell fates via concentration-gradients in the embryos where cells transduce this extracellular information into gene expression profiles and cell fate decisions. How receiving cells decode and quantify BMP2/4 signals is hardly understood. There is little data on the quantitative relationships between signal input, transducing molecules, their states and location, and ultimately their ability to integrate graded systemic inputs and generate qualitative responses. Understanding this signaling network on a quantitative level should be considered a prerequisite for efficient pathway modulation, as the BMP pathway is a prime target for therapeutic invention. Hence, we quantified the spatial distribution of the main signal transducer of the BMP2/4 pathway in response to different types and levels of stimuli in c2c12 cells. We found that the subcellular localization of Smad1 is independent of ligand concentration. In contrast, Smad1 phosphorylation levels relate proportionally to BMP2 ligand concentrations and they are entirely located in the nucleus. Interestingly, we found that BMP2 stimulates target gene expression in non-linear, wave-like forms. Amplitudes showed a clear concentration-dependency, for sustained and transient stimulation. We found that even burst-stimulation triggers gene-expression wave-like modulations that are detectable for at least 30 h. Finally, we show here that target gene expression oscillations depend on receptor kinase activity, as the kinase drives further expression pulses without receptor reactivation and the target gene expression breaks off after inhibitor treatment in c2c12 cells.}, language = {en} } @article{HerpinAdolfiNicoletal.2013, author = {Herpin, Amaury and Adolfi, Mateus C. and Nicol, Barbara and Hinzmann, Maria and Schmidt, Cornelia and Klughammer, Johanna and Engel, Mareen and Tanaka, Minoru and Guiguen, Yann and Schartl, Manfred}, title = {Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination}, series = {Molecular Biology and Evolution}, volume = {30}, journal = {Molecular Biology and Evolution}, number = {10}, doi = {10.1093/molbev/mst130}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132262}, pages = {2328-2346}, year = {2013}, abstract = {Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.}, language = {en} } @article{YanHongChenetal.2013, author = {Yan, Yan and Hong, Ni and Chen, Tiansheng and Li, Mingyou and Wang, Tiansu and Guan, Guijun and Qiao, Yongkang and Chen, Songlin and Schartl, Manfred and Li, Chang-Ming and Hong, Yunhan}, title = {p53 Gene Targeting by Homologous Recombination in Fish ES Cells}, series = {PLoS One}, volume = {8}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0059400}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133416}, pages = {e59400}, year = {2013}, abstract = {Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes). Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7\%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5\%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6\% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.}, language = {en} } @article{ForconiCanapaBaruccaetal.2013, author = {Forconi, Mariko and Canapa, Adriana and Barucca, Marco and Biscotti, Maria A. and Capriglione, Teresa and Buonocore, Francesco and Fausto, Anna M. and Makapedua, Daisy M. and Pallavicini, Alberto and Gerdol, Marco and De Moro, Gianluca and Scapigliati, Giuseppe and Olmo, Ettore and Schartl, Manfred}, title = {Characterization of Sex Determination and Sex Differentiation Genes in Latimeria}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0056006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130995}, pages = {e56006}, year = {2013}, abstract = {Genes involved in sex determination and differentiation have been identified in mice, humans, chickens, reptiles, amphibians and teleost fishes. However, little is known of their functional conservation, and it is unclear whether there is a common set of genes shared by all vertebrates. Coelacanths, basal Sarcopterygians and unique "living fossils", could help establish an inventory of the ancestral genes involved in these important developmental processes and provide insights into their components. In this study 33 genes from the genome of Latimeria chalumnae and from the liver and testis transcriptomes of Latimeria menadoensis, implicated in sex determination and differentiation, were identified and characterized and their expression levels measured. Interesting findings were obtained for GSDF, previously identified only in teleosts and now characterized for the first time in the sarcopterygian lineage; FGF9, which is not found in teleosts; and DMRT1, whose expression in adult gonads has recently been related to maintenance of sexual identity. The gene repertoire and testis-specific gene expression documented in coelacanths demonstrate a greater similarity to modern fishes and point to unexpected changes in the gene regulatory network governing sexual development.}, language = {en} } @article{KangSchartlWalteretal.2013, author = {Kang, Ji Hyoun and Schartl, Manfred and Walter, Ronald B. and Meyer, Axel}, title = {Comprehensive phylogenetic analysis of all species of swordtails and platies (Pisces: Genus Xiphophorus) uncovers a hybrid origin of a swordtail fish, Xiphophorus monticolus, and demonstrates that the sexually selected sword originated in the ancestral lineage of the genus, but was lost again secondarily}, series = {BMC Evolutionary Biology}, volume = {13}, journal = {BMC Evolutionary Biology}, number = {25}, issn = {1471-2148}, doi = {10.1186/1471-2148-13-25}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121853}, year = {2013}, abstract = {Background: Males in some species of the genus Xiphophorus, small freshwater fishes from Meso-America, have an extended caudal fin, or sword - hence their common name "swordtails". Longer swords are preferred by females from both sworded and - surprisingly also, non-sworded (platyfish) species that belong to the same genus. Swordtails have been studied widely as models in research on sexual selection. Specifically, the pre-existing bias hypothesis was interpreted to best explain the observed bias of females in presumed ancestral lineages of swordless species that show a preference for assumed derived males with swords over their conspecific swordless males. However, many of the phylogenetic relationships within this genus still remained unresolved. Here we construct a comprehensive molecular phylogeny of all 26 known Xiphophorus species, including the four recently described species (X. kallmani, X. mayae, X. mixei and X. monticolus). We use two mitochondrial and six new nuclear markers in an effort to increase the understanding of the evolutionary relationships among the species in this genus. Based on the phylogeny, the evolutionary history and character state evolution of the sword was reconstructed and found to have originated in the common ancestral lineage of the genus Xiphophorus and that it was lost again secondarily. Results: We estimated the evolutionary relationships among all known species of the genus Xiphophorus based on the largest set of DNA markers so far. The phylogeny indicates that one of the newly described swordtail species, Xiphophorus monticolus, is likely to have arisen through hybridization since it is placed with the southern platyfish in the mitochondrial phylogeny, but with the southern swordtails in the nuclear phylogeny. Such discordance between these two types of markers is a strong indication for a hybrid origin. Additionally, by using a maximum likelihood approach the possession of the sexually selected sword trait is shown to be the most likely ancestral state for the genus Xiphophorus. Further, we provide a well supported estimation of the phylogenetic relationships between the previously unresolved northern swordtail groups. Conclusions: This comprehensive molecular phylogeny of the entire genus Xiphophorus provides evidence that a second swordtail species, X. monticolus, arose through hybridization. Previously, we demonstrated that X. clemenciae, another southern swordtail species, arose via hybridization. These findings highlight the potential key role of hybridization in the evolution of this genus and suggest the need for further investigations into how hybridization contributes to speciation more generally.}, language = {en} } @article{HaydnHufnagelGrimmetal.2014, author = {Haydn, Johannes M. and Hufnagel, Anita and Grimm, Johannes and Maurus, Katja and Schartl, Manfred and Meierjohann, Svenja}, title = {The MAPK pathway as an apoptosis enhancer in melanoma}, series = {Oncotarget}, volume = {5}, journal = {Oncotarget}, number = {13}, issn = {1949-2553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120649}, pages = {5040-53}, year = {2014}, abstract = {Inhibition of RAF/MEK/ERK signaling is beneficial for many patients with BRAFV600E-mutated melanoma. However, primary and secondary resistances restrict long-lasting therapy success. Combination therapies are therefore urgently needed. Here, we evaluate the cellular effect of combining a MEK inhibitor with a genotoxic apoptosis inducer. Strikingly, we observed that an activated MAPK pathway promotes in several melanoma cell lines the pro-apoptotic response to genotoxic stress, and MEK inhibition reduces intrinsic apoptosis. This goes along with MEK inhibitor induced increased RAS and P-AKT levels. The protective effect of the MEK inhibitor depends on PI3K signaling, which prevents the induction of pro-apoptotic PUMA that mediates apoptosis after DNA damage. We could show that the MEK inhibitor dependent feedback loop is enabled by several factors, including EGF receptor and members of the SPRED family. The simultaneous knockdown of SPRED1 and SPRED2 mimicked the effects of MEK inhibitor such as PUMA repression and protection from apoptosis. Our data demonstrate that MEK inhibition of BRAFV600E-positive melanoma cells can protect from genotoxic stress, thereby achieving the opposite of the intended anti-tumorigenic effect of the combination of MEK inhibitor with inducers of intrinsic apoptosis.}, language = {en} } @article{AdolfiCarreiraJesusetal.2015, author = {Adolfi, Mateus C. and Carreira, Ana C. O. and Jesus, L{\´a}zaro W. O. and Bogerd, Jan and Funes, Rejane M. and Schartl, Manfred and Sogayar, Mari C. and Borella, Maria I.}, title = {Molecular cloning and expression analysis of dmrt1 and sox9 during gonad development and male reproductive cycle in the lambari fish, Astyanax altiparanae}, series = {Reproductive Biology and Endocrinology}, volume = {13}, journal = {Reproductive Biology and Endocrinology}, number = {2}, doi = {10.1186/1477-7827-13-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126486}, year = {2015}, abstract = {Background The dmrt1 and sox9 genes have a well conserved function related to testis formation in vertebrates, and the group of fish presents a great diversity of species and reproductive mechanisms. The lambari fish (Astyanax altiparanae) is an important Neotropical species, where studies on molecular level of sex determination and gonad maturation are scarce. Methods Here, we employed molecular cloning techniques to analyze the cDNA sequences of the dmrt1 and sox9 genes, and describe the expression pattern of those genes during development and the male reproductive cycle by qRT-PCR, and related to histology of the gonad. Results Phylogenetic analyses of predicted amino acid sequences of dmrt1 and sox9 clustered A. altiparanae in the Ostariophysi group, which is consistent with the morphological phylogeny of this species. Studies of the gonad development revealed that ovary formation occurred at 58 days after hatching (dah), 2 weeks earlier than testis formation. Expression studies of sox9 and dmrt1 in different tissues of adult males and females and during development revealed specific expression in the testis, indicating that both genes also have a male-specific role in the adult. During the period of gonad sex differentiation, dmrt1 seems to have a more significant role than sox9. During the male reproductive cycle dmrt1 and sox9 are down-regulated after spermiation, indicating a role of these genes in spermatogenesis. Conclusions For the first time the dmrt1 and sox9 were cloned in a Characiformes species. We show that both genes have a conserved structure and expression, evidencing their role in sex determination, sex differentiation and the male reproductive cycle in A. altiparanae. These findings contribute to a better understanding of the molecular mechanisms of sex determination and differentiation in fish.}, language = {en} } @article{Schartl2014, author = {Schartl, Manfred}, title = {Beyond the zebrafish: diverse fish species for modeling human disease}, series = {Disease Models \& Mechanisms}, volume = {7}, journal = {Disease Models \& Mechanisms}, number = {2}, issn = {1754-8411}, doi = {10.1242/dmm.012245}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119919}, year = {2014}, abstract = {In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.}, language = {en} } @article{TomaszkiewiczChalopinSchartletal.2014, author = {Tomaszkiewicz, Marta and Chalopin, Domitille and Schartl, Manfred and Galiana, Delphine and Volff, Jean-Nicolas}, title = {A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon}, series = {BMC Genetics}, volume = {15}, journal = {BMC Genetics}, number = {44}, doi = {10.1186/1471-2156-15-44}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116746}, year = {2014}, abstract = {Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed. Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata). Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.}, language = {en} } @article{GarciaMatosShenetal.2014, author = {Garcia, Tzintzuni I. and Matos, Isa and Shen, Yingjia and Pabuwal, Vagmita and Coelho, Maria Manuela and Wakamatsu, Yuko and Schartl, Manfred and Walter, Ronald B.}, title = {Novel Method for Analysis of Allele Specific Expression in Triploid Oryzias latipes Reveals Consistent Pattern of Allele Exclusion}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {6}, issn = {1932-6203}, doi = {10.1371/journal.pone.0100250}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116000}, pages = {e100250}, year = {2014}, abstract = {Assessing allele-specific gene expression (ASE) on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types) and diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82\%) shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18\%) displayed a wide range of ASE levels. Interestingly the majority of genes (78\%) displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.}, language = {en} } @article{AdamMauelerSchartl1991, author = {Adam, Dieter and Maueler, Winfried and Schartl, Manfred}, title = {Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87584}, year = {1991}, abstract = {The melanoma inducing locus of Xiphophorus encodes a tumorigenic version of a novel putative receptor tyrosine kinase (Xmrk). To elucidate the mechanism of oncogenic activation of Xmrk, we compared the structure and expression of two oncogenic loci with the corresponding proto-oncogene. Only minor structural alterations were found to be specific for the oncogenic Xmrk genes. Marked overexpression of the oncogene transcripts in melanoma, which are approximately 1 kb shorter than the proto-oncogene transcript, correlates with the malignancy of the tumors. The tumor transcripts are derived from an alternative transcription start site that is used only in the oncogenic loci. Thus, oncogenic activation of the melanoma inducing Xmrk gene appears primarily to be due to novel transcriptional control and overexpression.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{SchartlWittbrodtMaeueleretal.1993, author = {Schartl, Manfred and Wittbrodt, J. and M{\"a}ueler, W. and Raulf, F. and Adam, D. and Hannig, G. and Telling, A. and Storch, F. and Andexinger, S. and Robertson, S. M.}, title = {Oncogenes and melanoma formation in Xiphoporus (Teleostei: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87149}, year = {1993}, abstract = {In Xiphophorus melanoma formation has been attributed by classical genetic findings to the overexpression of a cellular oncogene (Tu) due to elimination of the corresponding regulatory gene locus in hybrids. We have attempted to elucidate this phenomenon on the molecular biological level. Studies on the structure and expression of known proto-oncogenes revealed that several of these genes, especially the c-src gene of Xiphophorus, may act as effectors in establishing the neoplastic phenotype of the melanoma cells . However, these genes appear more to participate in secondary steps of tumorigenesis. Another gene, being termed Xmrk, which represents obviously a so far unknown proto-oncogene but with a cons iderably high similarity to the epidermal growth-factorreceptor gene, was mapped to the Tu-containing region of the chromosome. This gene shows features with respect to its structure and expression that seem to justify it to be regarded as a candidate for a gene involved in the primary processes leading to neoplastic transformation of pigment cells in Xiphophorus.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @incollection{SchartlErbeldingDenkHoelteretal.1993, author = {Schartl, Manfred and Erbelding-Denk, C. and H{\"o}lter, S. and Nanda, I. and Schmid, M. and Schr{\"o}der, J. H. and Epplen, J. T.}, title = {High mating success of low rank males in Limia perugiae (Pisces: Poeciliidae) as determined by DNA-fingerprinting}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87132}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1993}, abstract = {Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behaviour and access to the females. In general social dominance requires large investments which in turn may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups due to the difficulties of determining paternity by classical methods using non-molecular markers. DNA fingerprinting overcomes these problems offering the possibility to determine genetic relationships and mating patterns within larger groups. Using this approach we have recently shown (Schartl et al., 1993) that in the poeciliid fish Limia perugiae in small mating groups the dominant male has 100\% mating success, while in larger groups its contribution to the offspring unexpectedly drops to zero. The reproductive failure under such social conditions is explained by the inability of the ex-male to protect all the females simultaneously against mating attempts of his numerous subordinate competitors.}, subject = {DNS}, language = {en} } @article{MeyerSchartl1979, author = {Meyer, Manfred K. and Schartl, Manfred}, title = {Eine neue Xiphophorus-Art aus Vera Cruz, Mexiko : (Pisces: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87124}, year = {1979}, abstract = {Xiphophorus andersi n. sp. from the Rio Atoyac, Vera Cruz, Mexico is described: lang head, moderately slender body, large dark black spar at the basis of the anal fin; adult male with short sword-like caudal appendage; rip of ray 5a of gonopodium without a developed claw. Xiphophorus andersi n. sp. differs by the combination of distinct characters from all the other species of the genus known so far. The new species shows features of both the so-called platyfish species group and the so-called swordtail species group.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{SchartlSchroeder1987, author = {Schartl, Manfred and Schr{\"o}der, Johannes Horst}, title = {A new species of the genus Xiphophorus Heckel 1848, endemic to northern Coahuila, Mexico (Pisces: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87117}, year = {1987}, abstract = {Xiphophorus meyeri n. sp. is described as an endemic to Muzquiz, Coahuila, Mexico. It appears to be the northernmost species of the genus. The new species is related to X. couchianus and X. gordoni, but differs morphologically from those by dorsal fin ray number, by the expression of some gonopodial features and most markedly by the appearance of macromelanophores or tr-melanophores.}, subject = {Schwertkr{\"a}pfling}, language = {en} } @article{WinklerWittbrodtLammersetal.1994, author = {Winkler, Christoph and Wittbrodt, Joachim and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred}, title = {Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87107}, year = {1994}, abstract = {Xmrk encodes a subclass 1 receptor tyrosine kinase (RTK) which has been cloned from the melanomainducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to ldnase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (bTGF(X), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of tbe RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating tbe significance of autocrine stimulation in RTK induced tumors in vertebrales.}, subject = {Japank{\"a}rpfling}, language = {en} } @article{WinklerHongWittbrodtetal.1992, author = {Winkler, Christoph and Hong, Yunhan and Wittbrodt, Joachim and Schartl, Manfred}, title = {Analysis of heterologous and homologous promoters and enhancers in vitro and in vivo by gene transfer into Japanese medaka (Oryzias latipes) and Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86796}, year = {1992}, abstract = {Efficient expression systems are required for analysis of gene regulation and function in teleost fish. To develop such systems, a nurober of inducible or constitutive promoter and enhancer sequences of fish or higher vertebrate origin were tested for activity in a variety of fish celllines andin embryos of the Japanese medaka fish (Oryzias latipes) and Xiphophorus. The activity of the different promoterenhancer combinations were quantitated. Considerable differences were found for some constructs if tested in vitro or in vivo. From the data obtained, a set of expression vectors for basic research as weH as for aquaculture purposes were established.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{FoersterSchartl1987, author = {Foerster, Wolfgang and Schartl, Manfred}, title = {Karyotype and isozyme patterns of five species of Aulonocara REGAN, 1922}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86774}, year = {1987}, abstract = {No abstract available.}, subject = {Aulonocara}, language = {en} }