TY  - JOUR
A1  - Herpin, Amaury
A1  - Adolfi, Mateus C.
A1  - Nicol, Barbara
A1  - Hinzmann, Maria
A1  - Schmidt, Cornelia
A1  - Klughammer, Johanna
A1  - Engel, Mareen
A1  - Tanaka, Minoru
A1  - Guiguen, Yann
A1  - Schartl, Manfred
T1  - Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination
JF  - Molecular Biology and Evolution
N2  - 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.
KW  - gonadal development
KW  - divergent expression regulation
KW  - gene regulatory network evolution
KW  - adaptive evolution
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132262
VL  - 30
IS  - 10
ER  - 
TY  - JOUR
A1  - Klughammer, Johanna
A1  - Dittrich, Marcus
A1  - Blom, Jochen
A1  - Mitesser, Vera
A1  - Vogel, Ulrich
A1  - Frosch, Matthias
A1  - Goesmann, Alexander
A1  - Müller, Tobias
A1  - Schoen, Christoph
T1  - Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease
JF  - PLoS ONE
N2  - Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo.
KW  - blood
KW  - comparative genomics
KW  - throat
KW  - genetic loci
KW  - Neisseria meningitidis
KW  - genomic libraries
KW  - genome sequencing
KW  - sequence assembly tools
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159547
VL  - 12
IS  - 1
ER  -