Life history effects on the molecular clock of autosomes and sex chromosomes

Abstract

One of the foundational results in molecular evolution is that the rate at which neutral substitutions accumulate on a lineage equals the rate at which mutations arise. Traits that affect rates of mutation therefore also affect the phylogenetic "molecular clock." We consider the effects of sex-specific generation times and mutation rates in species with two sexes. In particular, we focus on the effects that the age of onset of male puberty and rates of spermatogenesis have likely had in hominids (great apes), considering a model that approximates features of the mutational process in mammals, birds, and some other vertebrates. As we show, this model can account for a number of seemingly disparate observations: notably, the puzzlingly low X-to-autosome ratios of substitution rates in humans and chimpanzees and differences in rates of autosomal substitutions among hominine lineages (i.e., humans, chimpanzees, and gorillas). The model further suggests how to translate pedigree-based estimates of human mutation rates into split times among extant hominoids (apes), given sex-specific life histories. In so doing, it largely bridges the gap reported between estimates of split times based on fossil and molecular evidence, in particular suggesting that the human-chimpanzee split may have occurred as recently as 6.6 Mya. The model also implies that the "generation time effect" should be stronger in short-lived species, explaining why the generation time has a major influence on yearly substitution rates in mammals but only a subtle one in human pedigrees. molecular clock | mutational slowdown | generation time effect | human-chimpanzee split | male mutation bias M ost of our inferences about species split times on short phylogenetic timescales rely on the neutral molecular clock. According to the neutral theory, the number of substitutions K that accumulate in a lineage over T years (e.g., since the split from another species) is K = ðu=GÞT, where u and G are the average mutation rate per generation and average generation time, respectively (1). Inferring split times therefore requires estimates of the yearly mutation rate u=G on the lineage in question. Such estimates generally derive from securely dated fossils on other lineages or from measurements of mutation rates in extant species (2-5). Using these estimates for dating thus necessitates an understanding of the way that yearly mutation rates may change over time.Neutral substitution patterns in mammals offer some insights. Variation in yearly mutation rates on phylogenetic timescales can be assessed by comparing the number of neutral substitutions along two branches leading from a common ancestor to extant species. These comparisons show marked variation in yearly rates on autosomes. For example, there are 50% fewer substitutions on the human branch compared with rodents (6) and 25% fewer compared with baboons, with more moderate differences among hominine lineages (6-9). The average yearly rates are also negatively correlated with generation times (and their correl...

Overlooked roles of DNA damage and maternal age in generating human germline mutations

“…Our findings also carry implications for the differences in mutation rates that have been reported across populations and species (e.g., Hwang and Green, 2004;Moorjani et al, 2016). Within mammals, an older age of reproduction of a species is associated with a decreased ratio of X to autosome divergence (Makova and Li, 2002;Wilson-Sayres et al, 2011)(interpreted as higher male-to-female mutation ratios; but see Amster and Sella, 2016; an older age of reproduction is also correlated with a lower substitutions rate, with a much weaker relationship seen for CpG transitions (Li and Tanimura, 1987;Kim et al, 2006;Ségurel, Wyman and Przeworski, 2014;Moorjani et al, 2016). These observations have been widely interpreted as supporting a replicative origin of most non-CpG transitions (Li et al, 1996;Kim et al, 2006;Wilson-Sayres et al, 2011;Ségurel, Wyman and Przeworski, 2014;Moorjani et al, 2016).…”

“…One possibility is that inter-species differences in the male-to-female mutation ratio and in substitution rates instead reflect changes in the ratio of paternal and maternal ages at reproduction (Fig. 2B) (Amster and Sella, 2016) and in rates of DNA damage (e.g., metabolic rates) that covary with life history traits (Martin and Palumbi, 1993;Wilson-Sayres et al, 2011).…”

Bayesian Node Dating based on Probabilities of Fossil Sampling Supports Trans-Atlantic Dispersal of Cichlid Fishes

“…If the time units used in these simulations are considered to be million years, the sampling and diversification rates used here are comparable to those found in empirical data sets (Jetz et al 2012;Stadler and Bokma 2013;Rabosky et al 2013; Supplementary Table S1). In separate sets of simulations, branch-specific substitution rates were modeled either with an uncorrelated molecular clock (Drummond et al 2006), or with an autocorrelated molecular clock that accounts for the heritability of factors influencing rate variation (such as body mass, longevity, and generation time; Nabholz et al 2008;Amster and Sella 2016) and may therefore model rate evolution more realistically than the uncorrelated molecular clock (Lepage et al 2007). For both types of branch rate variation, we used a mean rate of 4 × 10 −3 substitutions per site per time unit and a variance parameter of 1.6 × 10 −5 .…”

“…by branch-rate autocorrelation (Supplementary Figure S3b). In practice, autocorrelation of branch-specific substitution rates can rarely be excluded, and may be present also in teleost fishes, as many factors influencing rate variation are heritable in vertebrates (Nabholz et al 2008;Amster and Sella 2016). Second, while our molecular dataset is composed of both nuclear and mitochondrial sequences, nuclear sequences were available to a greater degree for taxa outside of Cichlidae, and may be underrepresented for clades within this family.…”

Evidence of a chimpanzee-sized ancestor of humans but a gibbon-sized ancestor of apes

“…One important reason for this omission is the paucity of African fossil hominids during the period when the chimpanzee and human lineages are believed to have diverged, perhaps 4–6 Ma (million years ago) 17 or earlier at 6–8 Ma 18–20 , with the notable exceptions of putative basal hominins Orrorin tugenensis (~6 Ma) 21 , Sahelanthropus tchadensis (6–7 Ma) 22 , Ardipithecus kadabba (5.5–6.4 Ma) 23 , and the later Ardipithecus ramidus (4.4 Ma) 7 . In addition, body sizes in the more well-sampled Miocene hominoid (all living and extant apes and humans) taxa (e.g., Proconsul ) appear to be extremely variable (e.g., refs.…”