Strong Variations of Mitochondrial Mutation Rate across Mammals--the Longevity Hypothesis

Abstract

Mitochondrial DNA (mtDNA) is the most popular marker of molecular diversity in animals, primarily because of its elevated mutation rate. After >20 years of intensive usage, the extent of mitochondrial evolutionary rate variations across species, their practical consequences on sequence analysis methods, and the ultimate reasons for mtDNA hypermutability are still largely unresolved issues. Using an extensive cytochrome b data set, fossil data, and taking advantage of the decoupled dynamics of synonymous and nonsynonymous substitutions, we measure the lineage-specific mitochondrial mutation rate across 1,696 mammalian species and compare it with the nuclear rate. We report an unexpected 2 orders of magnitude mitochondrial mutation rate variation between lineages: cytochrome b third codon positions are renewed every 1-2 Myr, in average, in the fastest evolving mammals, whereas it takes >100 Myr in slow-evolving lineages. This result has obvious implications in the fields of molecular phylogeny, molecular dating, and population genetics. Variations of mitochondrial substitution rate across species are partly explained by body mass, longevity, and age of female sexual maturity. The classical metabolic rate and generation time hypothesis, however, do not fully explain the observed patterns, especially a stronger effect of longevity in long-lived than in short-lived species. We propose that natural selection tends to decrease the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial theory of aging.

DNA sequence diversity and the efficiency of natural selection in animal mitochondrial DNA

“…However, there is also evidence to suggest that patterns of molecular evolution are different between these two groups, which may suggest a difference in the relationship between π S and N e . For example, Nabholz et al (2008) have found that synonymous substitution rates are considerably lower in bats than in rodents: this could be because of lower mutation rates or longer generation times in bats than in rodents. In contrast, the shape parameter of the DFE estimated from the SFS mirrors the difference in slopes between high and low body mass and high and low metabolic rate, although in only the data set in which n = 5 is the difference significant.…”

Taller plants have lower rates of molecular evolution

“…As a result, generation time can provide a useful proxy of the overall rate of genome replication in animals, but is unlikely to do so in plants. This may explain why the evidence for the generation time hypothesis is very strong for animals [16][17][18] , but mixed for plants 1,[19][20][21] . Despite this, generation time will remain tightly associated with long-term rates of meiosis in plants, because an extant plant genome would have experienced one meiosis in each generation through which it has passed.…”

How closely does genetic diversity in finite populations conform to predictions of neutral theory? Large deficits in regions of low recombination

“…Second, mtDNA mutation rates differ across animal taxa (Nabholz et al, 2008a, but see Charlesworth, 2010 and Bazin et al (2006) did not correct for such differences. mtDNA silent site substitution rates and presumably mutation rates fall into high (flatworms, molluscs, annelid worms, bryozoans, arthropods, nematodes, echinoderms, tunicates and vertebrates) and low (angiosperms, fungi, sponges, corals, sea fans and Medusozoa) rates, with the former rates being about 10 times nuclear substitution rates and the latter about an order of magnitude slower (Hellberg, 2006).…”