The killifish Nothobranchius furzeri is the shortest-lived vertebrate that can be bred in the laboratory. Its rapid growth, early sexual maturation, fast aging, and arrested embryonic development (diapause) make it an attractive model organism in biomedical research. Here, we report a draft sequence of its genome that allowed us to uncover an intra-species Y chromosome polymorphism representing-in real time-different stages of sex chromosome formation that display features of early mammalian XY evolution "in action." Our data suggest that gdf6Y, encoding a TGF-β family growth factor, is the master sex-determining gene in N. furzeri. Moreover, we observed genomic clustering of aging-related genes, identified genes under positive selection, and revealed significant similarities of gene expression profiles between diapause and aging, particularly for genes controlling cell cycle and translation. The annotated genome sequence is provided as an online resource (http://www.nothobranchius.info/NFINgb).

BackgroundMammals display a wide range of variation in their lifespan. Investigating the molecular networks that distinguish long- from short-lived species has proven useful to identify determinants of longevity. Here, we compared the livers of young and old long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omics approach.ResultsWe found that NMR livers display a unique expression pattern of mitochondrial proteins that results in distinct metabolic features of their mitochondria. For instance, we observed a generally reduced respiration rate associated with lower protein levels of respiratory chain components, particularly complex I, and increased capacity to utilize fatty acids. Interestingly, we show that the same molecular networks are affected during aging in both NMRs and humans, supporting a direct link to the extraordinary longevity of both species. Finally, we identified a novel detoxification pathway linked to longevity and validated it experimentally in the nematode Caenorhabditis elegans.ConclusionsOur work demonstrates the benefits of integrating proteomic and transcriptomic data to perform cross-species comparisons of longevity-associated networks. Using a multispecies approach, we show at the molecular level that livers of NMRs display progressive age-dependent changes that recapitulate typical signatures of aging despite the negligible senescence and extraordinary longevity of these rodents.Electronic supplementary materialThe online version of this article (10.1186/s12915-018-0547-y) contains supplementary material, which is available to authorized users.

a b s t r a c tThe hypothesis is tested that some heat stress transcription factors (HSFs) are activated after formation of inter-or intramolecular disulfide bonds. Based on in silico analyses we identified conserved cysteinyl residues in AtHSFA8 that might function as redox sensors in plants. AtHSFA8 represents a redox-sensitive transcription factor since upon treatment of protoplasts with H 2 O 2 YFP-labeled HSFA8 was translocated to the nucleus in a time-dependent manner. Site-directed mutagenesis of the conserved residues Cys24 and Cys269 blocked translocation of HSFA8 to the nucleus. The findings concur with a model where HSFA8 functions as redox sensing transcription factor within the stress-responsive transcriptional network.

SummaryThe current molecular understanding of the aging process derives almost exclusively from the study of random or targeted single‐gene mutations in highly inbred laboratory species, mostly invertebrates. Little information is available as to the genetic mechanisms responsible for natural lifespan variation and the evolution of lifespan, especially in vertebrates. Here, we investigated the pattern of positive selection in annual (i.e., short‐lived) and nonannual (i.e., longer‐lived) African killifishes to identify a genomic substrate for evolution of annual life history (and reduced lifespan). We identified genes under positive selection in all steps of mitochondrial biogenesis: mitochondrial (mt) DNA replication, transcription from mt promoters, processing and stabilization of mt RNAs, mt translation, assembly of respiratory chain complexes, and electron transport chain. Signs of paralleled evolution (i.e., evolution in more than one branch of Nothobranchius phylogeny) are observed in four out of five steps. Moreover, some genes under positive selection in Nothobranchius are under positive selection also in long‐lived mammals such as bats and mole‐rats. Complexes of the respiratory chain are formed in a coordinates multistep process where nuclearly and mitochondrially encoded components are assembled and inserted into the inner mitochondrial membrane. The coordination of this process is named mitonuclear balance, and experimental manipulations of mitonuclear balance can increase longevity of laboratory species. Our data strongly indicate that these genes are also casually linked to evolution lifespan in vertebrates.

Many comparative genomics studies aim to find the genetic basis of species-specific phenotypic traits. A prevailing strategy is to search genome-wide for genes that evolved under positive selection based on the non-synonymous to synonymous substitution ratio. However, incongruent results largely due to high false positive rates indicate the need for standardization of quality criteria and software tools. Main challenges are the ortholog and isoform assignment, the high sensitivity of the statistical models to alignment errors and the imperative to parallelize large parts of the software. We developed the software tool PosiGene that (i) detects positively selected genes (PSGs) on genome-scale, (ii) allows analysis of specific evolutionary branches, (iii) can be used in arbitrary species contexts and (iv) offers visualization of the results for further manual validation and biological interpretation. We exemplify PosiGene's performance using simulated and real data. In the simulated data approach, we determined a false positive rate <1%. With real data, we found that 68.4% of the PSGs detected by PosiGene, were shared by at least one previous study that used the same set of species. PosiGene is a user-friendly, reliable tool for reproducible genome-wide identification of PSGs and freely available at https://github.com/gengit/PosiGene.