Parallel evolution of genes controlling mitonuclear balance in short-lived annual fishes

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.

Molecular signatures of longevity: Insights from cross-species comparative studies

“…The same was also observed for several other genes with positive selection signals in killifish (Sahm et al, 2017). POLRMT codes for mitochondrial RNA polymerase and showed positive selection signals in two branches of the short-lived killifish as well as in the long-lived Brandt’s bat.…”

“…POLRMT codes for mitochondrial RNA polymerase and showed positive selection signals in two branches of the short-lived killifish as well as in the long-lived Brandt’s bat. Tenascin ( TNC ) was positively selected in humans and the last common ancestor of mole rats, while collagen type IV alpha 2 ( COL4A2 ) was positively selected in naked mole rat and the last common ancestor of mole rats, and both genes also showed positive selection signals along the branch leading to the killifish N. furzeri , N. kadleci and N. kuhntae (Sahm et al, 2017). Furthermore, a significant number of genes coding for components of mitochondrial respiratory chain complex I, mitochondrial ribosome proteins, and proteins involved in mitochondrial biogenesis and respiratory chain complex assembly also showed positive selection in killifish (Sahm et al, 2017).…”

“…Tenascin ( TNC ) was positively selected in humans and the last common ancestor of mole rats, while collagen type IV alpha 2 ( COL4A2 ) was positively selected in naked mole rat and the last common ancestor of mole rats, and both genes also showed positive selection signals along the branch leading to the killifish N. furzeri , N. kadleci and N. kuhntae (Sahm et al, 2017). Furthermore, a significant number of genes coding for components of mitochondrial respiratory chain complex I, mitochondrial ribosome proteins, and proteins involved in mitochondrial biogenesis and respiratory chain complex assembly also showed positive selection in killifish (Sahm et al, 2017). In agreement, mitochondrial respiratory chain complex I was previously identified as a hub of gene modules whose expression correlated negatively with lifespan in killifish (Baumgart et al, 2016) and with lifespan of mammalian species (Fushan et al, 2015).…”

“…Partial pharmacological inhibition of complex I by the small molecule rotenone could result in 15% lifespan extension in killifish (Baumgart et al, 2016). Hence, the regulation of longevity and aging in both long-lived and short-lived species may involve the parallel evolution of the same set of genes and pathways (Sahm et al, 2017; Valenzano et al, 2015). …”

“…The central role of immune response was noted in naked mole rats (Kim et al, 2011), blind mole rats (Fang et al, 2014a), microbats (Seim et al, 2013; Zhang et al, 2013), and the brain of aging killifish (Baumgart et al, 2014). In killifish, mitochondrial respiratory chains showed positive selection signals (Sahm et al, 2017) and negative correlation with lifespan (Baumgart et al, 2014; Baumgart et al, 2016), and inhibition of complex I with rotenone could achieve 15% lifespan extension (Baumgart et al, 2016). …”