Abstract
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.
Highlights
The 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
If two branches of an evolutionary tree differ in a key phenotype, the genes under positive selection likely played a role in the evolution of that phenotype
In addition to sequence data presented previously (Reichwald et al, 2015), we obtained from GenBank the RefSeq mRNA sequences of the phylogenetically closest outgroups from Ovalentaria (Fig. 1) and analyzed the pattern of positive selection along three internal branches of the tree: The first branch corresponds to the last common ancestor (LCA) of all Nothobranchius spp. (N-branch) and it marks the transition to annual life cycle
Summary
The 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. Natural variability in lifespan across vertebrate species greatly exceeds the magnitude of life extension that has been obtained by single-gene manipulations, and a comparative approach may reveal novel genetic pathways that are responsible for evolution of lifespan. The increasing availability of sequenced genomes and transcriptomes of related species with differing lifespans can facilitate the identification of putative aging-related genes by analysis of positive selection. Positive selection on protein-coding sequences results in an increase in the rate of non-synonymous substitutions as compared with random genetic drift. Statistical models based on the ratio of non-synonymous to synonymous substitution rates (dN/dS) can identify specific amino acid codons within a given gene that evolved due to positive selection and are widely used in comparative genomics (Kosiol et al, 2008; Roux et al, 2014; Davies et al, 2015)
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