@article{LuBoswellBoswelletal.2018, author = {Lu, Yuan and Boswell, Mikki and Boswell, William and Kneitz, Susanne and Klotz, Barbara and Savage, Markita and Salinas, Raquel and Marks, Rebacca and Regneri, Janine and Postlethwait, John and Warren, Wesley C. and Schartl, Manfred and Walter, Ronald}, title = {Gene expression variation and parental allele inheritance in a Xiphophorus interspecies hybridization model}, series = {PLoS Genetics}, volume = {14}, journal = {PLoS Genetics}, doi = {10.1371/journal.pgen.1007875}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237318}, year = {2018}, abstract = {Understanding the genetic mechanisms underlying segregation of phenotypic variation through successive generations is important for understanding physiological changes and disease risk. Tracing the etiology of variation in gene expression enables identification of genetic interactions, and may uncover molecular mechanisms leading to the phenotypic expression of a trait, especially when utilizing model organisms that have well-defined genetic lineages. There are a plethora of studies that describe relationships between gene expression and genotype, however, the idea that global variations in gene expression are also controlled by genotype remains novel. Despite the identification of loci that control gene expression variation, the global understanding of how genome constitution affects trait variability is unknown. To study this question, we utilized Xiphophorus fish of different, but tractable genetic backgrounds (inbred, F1 interspecies hybrids, and backcross hybrid progeny), and measured each individual's gene expression concurrent with the degrees of inter-individual expression variation. We found, (a) F1 interspecies hybrids exhibited less variability than inbred animals, indicting gene expression variation is not affected by the fraction of heterozygous loci within an individual genome, and (b), that mixing genotypes in backcross populations led to higher levels of gene expression variability, supporting the idea that expression variability is caused by heterogeneity of genotypes of cis or trans loci. In conclusion, heterogeneity of genotype, introduced by inheritance of different alleles, accounts for the largest effects on global phenotypical variability.}, language = {en} } @article{HerpinSchmidtKneitzetal.2019, author = {Herpin, Amaury and Schmidt, Cornelia and Kneitz, Susanne and Gob{\´e}, Clara and Regensburger, Martina and Le Cam, Aur{\´e}lie and Montfort, J{\´e}rome and Adolfi, Mateus C. and Lillesaar, Christina and Wilhelm, Dagmar and Kraeussling, Michael and Mourot, Brigitte and Porcon, B{\´e}atrice and Pannetier, Ma{\"e}lle and Pailhoux, Eric and Ettwiller, Laurence and Dolle, Dirk and Guiguen, Yann and Schartl, Manfred}, title = {A novel evolutionary conserved mechanism of RNA stability regulates synexpression of primordial germ cell-specific genes prior to the sex-determination stage in medaka}, series = {PLoS Biology}, volume = {17}, journal = {PLoS Biology}, doi = {10.1371/journal.pbio.3000185}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320011}, year = {2019}, abstract = {Dmrt1 is a highly conserved transcription factor, which is critically involved in regulation of gonad development of vertebrates. In medaka, a duplicate of dmrt1—acting as master sex-determining gene—has a tightly timely and spatially controlled gonadal expression pattern. In addition to transcriptional regulation, a sequence motif in the 3′ UTR (D3U-box) mediates transcript stability of dmrt1 mRNAs from medaka and other vertebrates. We show here that in medaka, two RNA-binding proteins with antagonizing properties target this D3U-box, promoting either RNA stabilization in germ cells or degradation in the soma. The D3U-box is also conserved in other germ-cell transcripts, making them responsive to the same RNA binding proteins. The evolutionary conservation of the D3U-box motif within dmrt1 genes of metazoans—together with preserved expression patterns of the targeting RNA binding proteins in subsets of germ cells—suggest that this new mechanism for controlling RNA stability is not restricted to fishes but might also apply to other vertebrates.}, language = {en} } @article{MeyerSchloissnigFranchinietal.2021, author = {Meyer, Axel and Schloissnig, Siegfried and Franchini, Paolo and Du, Kang and Woltering, Joost M. and Irisarri, Iker and Wong, Wai Yee and Nowoshilow, Sergej and Kneitz, Susanne and Kawaguchi, Akane and Fabrizius, Andrej and Xiong, Peiwen and Dechaud, Corentin and Spaink, Herman P. and Volff, Jean-Nicolas and Simakov, Oleg and Burmester, Thorsten and Tanaka, Elly M. and Schartl, Manfred}, title = {Giant lungfish genome elucidates the conquest of land by vertebrates}, series = {Nature}, volume = {590}, journal = {Nature}, doi = {10.1038/s41586-021-03198-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370750}, pages = {284-289}, year = {2021}, abstract = {Lungfishes belong to lobe-fined fish (Sarcopterygii) that, in the Devonian period, 'conquered' the land and ultimately gave rise to all land vertebrates, including humans1,2,3. Here we determine the chromosome-quality genome of the Australian lungfish (Neoceratodus forsteri), which is known to have the largest genome of any animal. The vast size of this genome, which is about 14× larger than that of humans, is attributable mostly to huge intergenic regions and introns with high repeat content (around 90\%), the components of which resemble those of tetrapods (comprising mainly long interspersed nuclear elements) more than they do those of ray-finned fish. The lungfish genome continues to expand independently (its transposable elements are still active), through mechanisms different to those of the enormous genomes of salamanders. The 17 fully assembled lungfish macrochromosomes maintain synteny to other vertebrate chromosomes, and all microchromosomes maintain conserved ancient homology with the ancestral vertebrate karyotype. Our phylogenomic analyses confirm previous reports that lungfish occupy a key evolutionary position as the closest living relatives to tetrapods4,5, underscoring the importance of lungfish for understanding innovations associated with terrestrialization. Lungfish preadaptations to living on land include the gain of limb-like expression in developmental genes such as hoxc13 and sall1 in their lobed fins. Increased rates of evolution and the duplication of genes associated with obligate air-breathing, such as lung surfactants and the expansion of odorant receptor gene families (which encode proteins involved in detecting airborne odours), contribute to the tetrapod-like biology of lungfishes. These findings advance our understanding of this major transition during vertebrate evolution.}, language = {en} } @article{RheeChoiKimetal.2017, author = {Rhee, Jae-Sung and Choi, Beom-Soon and Kim, Jaebum and Kim, Bo-Mi and Lee, Young-Mi and Kim, Il-Chan and Kanamori, Akira and Choi, Ik-Young and Schartl, Manfred and Lee, Jae-Seong}, title = {Diversity, distribution, and significance of transposable elements in the genome of the only selfing hermaphroditic vertebrate Kryptolebias marmoratus}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/srep40121}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181329}, year = {2017}, abstract = {The Kryptolebias marmoratus is unique because it is the only selffertilizing hermaphroditic vertebrate, known to date. It primarily reproduces by internal self-fertilization in a mixed ovary/testis gonad. Here, we report on a high-quality genome assembly for the K. marmoratus South Korea (SK) strain highlighting the diversity and distribution of transposable elements (TEs). We find that K. marmoratus genome maintains number and composition of TEs. This can be an important genomic attribute promoting genome recombination in this selfing fish, while, in addition to a mixed mating strategy, it may also represent a mechanism contributing to the evolutionary adaptation to ecological pressure of the species. Future work should help clarify this point further once genomic information is gathered for other taxa of the family Rivulidae that do not self-fertilize. We provide a valuable genome resource that highlights the potential impact of TEs on the genome evolution of a fish species with an uncommon life cycle.}, language = {en} } @article{LuBierbachOrmannsetal.2021, author = {Lu, Yuan and Bierbach, David and Ormanns, Jenny and Warren, Wesley C. and Walter, Ronald B. and Schartl, Manfred}, title = {Fixation of allelic gene expression landscapes and expression bias pattern shape the transcriptome of the clonal Amazon molly}, series = {Genome Research}, volume = {31}, journal = {Genome Research}, doi = {10.1101/gr.268870.120}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369578}, pages = {372-379}, year = {2021}, abstract = {The Amazon molly is a unique clonal fish species that originated from an interspecies hybrid between Poecilia species P. mexicana and P. latipinna. It reproduces by gynogenesis, which eliminates paternal genomic contribution to offspring. An earlier study showed that Amazon molly shows biallelic expression for a large portion of the genome, leading to two main questions: (1) Are the allelic expression patterns from the initial hybridization event stabilized or changed during establishment of the asexual species and its further evolution? (2) Is allelic expression biased toward one parental allele a stochastic or adaptive process? To answer these questions, the allelic expression of P. formosa siblings was assessed to investigate intra- and inter-cohort allelic expression variability. For comparison, interspecies hybrids between P. mexicana and P. latipinna were produced in the laboratory to represent the P. formosa ancestor. We have identified inter-cohort and intra-cohort variation in parental allelic expression. The existence of inter-cohort divergence suggests functional P. formosa allelic expression patterns do not simply reflect the atavistic situation of the first interspecies hybrid but potentially result from long-term selection of transcriptional fitness. In addition, clonal fish show a transcriptional trend representing minimal intra-clonal variability in allelic expression patterns compared to the corresponding hybrids. The intra-clonal similarity in gene expression translates to sophisticated genetic functional regulation at the individuum level. These findings suggest the parental alleles inherited by P. formosa form tightly regulated genetic networks that lead to a stable transcriptomic landscape within clonal individuals.}, language = {en} } @article{LiZhangFanetal.2021, author = {Li, Ming and Zhang, Rui and Fan, Guangyi and Xu, Wenteng and Zhou, Qian and Wang, Lei and Li, Wensheng and Pang, Zunfang and Yu, Mengjun and Liu, Qun and Liu, Xin and Schartl, Manfred and Chen, Songlin}, title = {Reconstruction of the Origin of a Neo-Y Sex Chromosome and Its Evolution in the Spotted Knifejaw, Oplegnathus punctatus}, series = {Molecular Biology and Evolution}, volume = {38}, journal = {Molecular Biology and Evolution}, doi = {10.1093/molbev/msab056}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364215}, pages = {2615-2626}, year = {2021}, abstract = {Sex chromosomes are a peculiar constituent of the genome because the evolutionary forces that fix the primary sex-determining gene cause genic degeneration and accumulation of junk DNA in the heterogametic partner. One of the most spectacular phenomena in sex chromosome evolution is the occurrence of neo-Y chromosomes, which lead to X1X2Y sex-determining systems. Such neo-sex chromosomes are critical for understanding the processes of sex chromosome evolution because they rejuvenate their total gene content. We assembled the male and female genomes at the chromosome level of the spotted knifejaw (Oplegnathus punctatus), which has a cytogenetically recognized neo-Y chromosome. The full assembly and annotation of all three sex chromosomes allowed us to reconstruct their evolutionary history. Contrary to other neo-Y chromosomes, the fusion to X2 is quite ancient, estimated at 48 Ma. Despite its old age and being even older in the X1 homologous region which carries a huge inversion that occurred as early as 55-48 Ma, genetic degeneration of the neo-Y appears to be only moderate. Transcriptomic analysis showed that sex chromosomes harbor 87 genes, which may serve important functions in the testis. The accumulation of such male-beneficial genes, a large inversion on the X1 homologous region and fusion to X2 appear to be the main drivers of neo-Y evolution in the spotted knifejaw. The availability of high-quality assemblies of the neo-Y and both X chromosomes make this fish an ideal model for a better understanding of the variability of sex determination mechanisms and of sex chromosome evolution.}, language = {en} } @article{KuhlGuiguenHoehneetal.2021, author = {Kuhl, Heiner and Guiguen, Yann and H{\"o}hne, Christin and Kreuz, Eva and Du, Kang and Klopp, Christophe and Lopez-Roques,, C{\´e}line and Yebra-Pimentel, Elena Santidrian and Ciorpac, Mitica and Gessner, J{\"o}rn and Holostenco, Daniela and Kleiner, Wibke and Kohlmann, Klaus and Lamatsch, Dunja K. and Prokopov, Dmitry and Bestin, Anastasia and Bonpunt, Emmanuel and Debeuf, Bastien and Haffray, Pierrick and Morvezen, Romain and Patrice, Pierre and Suciu, Radu and Dirks, Ron and Wuertz, Sven and Kloas, Werner and Schartl, Manfred and St{\"o}ck, Matthias}, title = {A 180 Myr-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes}, series = {Philosophical Transactions of the Royal Society B}, volume = {376}, journal = {Philosophical Transactions of the Royal Society B}, doi = {10.1098/rstb.2020.0089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363050}, year = {2021}, abstract = {Several hypotheses explain the prevalence of undifferentiated sex chromosomes in poikilothermic vertebrates. Turnovers change the master sex determination gene, the sex chromosome or the sex determination system (e.g. XY to WZ). Jumping master genes stay main triggers but translocate to other chromosomes. Occasional recombination (e.g. in sex-reversed females) prevents sex chromosome degeneration. Recent research has uncovered conserved heteromorphic or even homomorphic sex chromosomes in several clades of non-avian and non-mammalian vertebrates. Sex determination in sturgeons (Acipenseridae) has been a long-standing basic biological question, linked to economical demands by the caviar-producing aquaculture. Here, we report the discovery of a sex-specific sequence from sterlet (Acipenser ruthenus). Using chromosome-scale assemblies and pool-sequencing, we first identified an approximately 16 kb female-specific region. We developed a PCR-genotyping test, yielding female-specific products in six species, spanning the entire phylogeny with the most divergent extant lineages (A. sturio, A. oxyrinchus versus A. ruthenus, Huso huso), stemming from an ancient tetraploidization. Similar results were obtained in two octoploid species (A. gueldenstaedtii, A. baerii). Conservation of a female-specific sequence for a long period, representing 180 Myr of sturgeon evolution, and across at least one polyploidization event, raises many interesting biological questions. We discuss a conserved undifferentiated sex chromosome system with a ZZ/ZW-mode of sex determination and potential alternatives. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)'.}, language = {en} } @article{LuBoswellBoswelletal.2019, author = {Lu, Yuan and Boswell, Wiliam and Boswell, Mikki and Klotz, Barbara and Kneitz, Susanne and Regneri, Janine and Savage, Markita and Mendoza, Cristina and Postlethwait, John and Warren, Wesley C. and Schartl, Manfred and Walter, Ronald B.}, title = {Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-018-36656-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237322}, year = {2019}, abstract = {Cell culture and protein target-based compound screening strategies, though broadly utilized in selecting candidate compounds, often fail to eliminate candidate compounds with non-target effects and/or safety concerns until late in the drug developmental process. Phenotype screening using intact research animals is attractive because it can help identify small molecule candidate compounds that have a high probability of proceeding to clinical use. Most FDA approved, first-in-class small molecules were identified from phenotypic screening. However, phenotypic screening using rodent models is labor intensive, low-throughput, and very expensive. As a novel alternative for small molecule screening, we have been developing gene expression disease profiles, termed the Transcriptional Disease Signature (TDS), as readout of small molecule screens for therapeutic molecules. In this concept, compounds that can reverse, or otherwise affect known disease-associated gene expression patterns in whole animals may be rapidly identified for more detailed downstream direct testing of their efficacy and mode of action. To establish proof of concept for this screening strategy, we employed a transgenic strain of a small aquarium fish, medaka (Oryzias latipes), that overexpresses the malignant melanoma driver gene xmrk, a mutant egfr gene, that is driven by a pigment cell-specific mitf promoter. In this model, melanoma develops with 100\% penetrance. Using the transgenic medaka malignant melanoma model, we established a screening system that employs the NanoString nCounter platform to quantify gene expression within custom sets of TDS gene targets that we had previously shown to exhibit differential transcription among xmrk-transgenic and wild-type medaka. Compound-modulated gene expression was identified using an internet-accessible custom-built data processing pipeline. The effect of a given drug on the entire TDS profile was estimated by comparing compound-modulated genes in the TDS using an activation Z-score and Kolmogorov-Smirnov statistics. TDS gene probes were designed that target common signaling pathways that include proliferation, development, toxicity, immune function, metabolism and detoxification. These pathways may be utilized to evaluate candidate compounds for potential favorable, or unfavorable, effects on melanoma-associated gene expression. Here we present the logistics of using medaka to screen compounds, as well as, the development of a user-friendly NanoString data analysis pipeline to support feasibility of this novel TDS drug-screening strategy.}, language = {en} } @article{KimAmoresKangetal.2019, author = {Kim, Bo-Mi and Amores, Angel and Kang, Seunghyun and Ahn, Do-Hwan and Kim, Jin-Hyoung and Kim, Il-Chan and Lee, Jun Hyuck and Lee, Sung Gu and Lee, Hyoungseok and Lee, Jungeun and Kim, Han-Woo and Desvignes, Thomas and Batzel, Peter and Sydes, Jason and Titus, Tom and Wilson, Catherine A. and Catchen, Julian M. and Warren, Wesley C. and Schartl, Manfred and Detrich, H. William III and Postlethwait, John H. and Park, Hyun}, title = {Antarctic blackfin icefish genome reveals adaptations to extreme environments}, series = {Nature Ecology \& Evolution}, volume = {3}, journal = {Nature Ecology \& Evolution}, doi = {10.1038/s41559-019-0812-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325811}, pages = {469-478}, year = {2019}, abstract = {Icefishes (suborder Notothenioidei; family Channichthyidae) are the only vertebrates that lack functional haemoglobin genes and red blood cells. Here, we report a high-quality genome assembly and linkage map for the Antarctic blackfin icefish Chaenocephalus aceratus, highlighting evolved genomic features for its unique physiology. Phylogenomic analysis revealed that Antarctic fish of the teleost suborder Notothenioidei, including icefishes, diverged from the stickleback lineage about 77 million years ago and subsequently evolved cold-adapted phenotypes as the Southern Ocean cooled to sub-zero temperatures. Our results show that genes involved in protection from ice damage, including genes encoding antifreeze glycoprotein and zona pellucida proteins, are highly expanded in the icefish genome. Furthermore, genes that encode enzymes that help to control cellular redox state, including members of the sod3 and nqo1 gene families, are expanded, probably as evolutionary adaptations to the relatively high concentration of oxygen dissolved in cold Antarctic waters. In contrast, some crucial regulators of circadian homeostasis (cry and per genes) are absent from the icefish genome, suggesting compromised control of biological rhythms in the polar light environment. The availability of the icefish genome sequence will accelerate our understanding of adaptation to extreme Antarctic environments.}, language = {en} } @article{FranchiniJonesXiongetal.2018, author = {Franchini, Paolo and Jones, Julia C. and Xiong, Peiwen and Kneitz, Susanne and Gompert, Zachariah and Warren, Wesley C. and Walter, Ronald B. and Meyer, Axel and Schartl, Manfred}, title = {Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-07648-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228396}, year = {2018}, abstract = {The remarkable diversity of sex determination mechanisms known in fish may be fuelled by exceptionally high rates of sex chromosome turnovers or transitions. However, the evolutionary causes and genomic mechanisms underlying this variation and instability are yet to be understood. Here we report on an over 30-year evolutionary experiment in which we tested the genomic consequences of hybridisation and selection between two Xiphophorus fish species with different sex chromosome systems. We find that introgression and imposing selection for pigmentation phenotypes results in the retention of an unexpectedly large maternally derived genomic region. During the hybridisation process, the sex-determining region of the X chromosome from one parental species was translocated to an autosome in the hybrids leading to the evolution of a new sex chromosome. Our results highlight the complexity of factors contributing to patterns observed in hybrid genomes, and we experimentally demonstrate that hybridisation can catalyze rapid evolution of a new sex chromosome.}, language = {en} }