Experimental estimates of germline mutation rate in eukaryotes: a phylogenetic meta-analysis

Abstract

Mutation is the ultimate source of all genetic variation, and over the last 10 years the ready availability of whole-genome sequencing has permitted direct estimation of mutation rate for many non-model species across the tree of life. In this meta-analysis, we make a comprehensive search of the literature for mutation rate estimates in eukaryotes, identifying 140 mutation accumulation (MA) and parent-offspring (PO) sequencing studies covering 134 species. Based on these data, we revisit differences in the single-nucleotide mutation (SNM) rate between different phylogenetic lineages and update the known relationships between mutation rate and generation time, genome size, and nucleotide diversity-while accounting for phylogenetic nonindependence. We do not find a significant difference between MA and PO in estimated mutation rates, but we confirm that mammal and plant lineages have higher mutation rates than arthropods and that unicellular eukaryotes have the lowest mutation rates. We find that mutation rates are higher in species with longer generation times and larger genome sizes, even when accounting for phylogenetic relationships. Moreover, although nucleotide diversity is positively correlated with mutation rate, the gradient of the relationship is significantly less than one (on a logarithmic scale), consistent with higher mutation rates in populations with smaller effective size. For the 29 species for which data are available, we find that indel mutation rates are positively correlated with nucleotide mutation rates and that short deletions are generally more common than short insertions. Nevertheless, despite recent progress, no estimates of either SNM or indel mutation rates are available for the majority of deeply branching eukaryotic lineages-or even for most animal phyla. Even among charismatic megafauna, experimental mutation rate estimates remain unknown for amphibia and scarce for reptiles and fish.

Keywords: de novo mutation rate; eukaryotes; indels; phylogeny.

Figure 1.

A summary of de novo mutation rate studies published up to 21 September 2022. (A) The proportion of studies in different taxonomic groups. (B) The number of studies by year. MA = mutation accumulation studies, PO = parent–offspring studies.

Figure 2.

A phylogenetic meta-analysis of SNM rates for different species identified from the literature. Mutation rates and 95% CIs were estimated using a PGLMM. For each annotated clade, we estimated the rate for their most recent common ancestor (clades marked in color; estimates in dashed lines and below taxon icons to the right). The vertical black dashed line indicates the mutation rate of common ancestor of the tree. PGLMM = phylogenetic generalized linear mixed model; SNM = single-nucleotide mutation.

Figure 3.

Phylogenetic linear regressions of SNM rate on (A) generation time for 116 species and (B) genome size for 108 species. The solid black lines represent simple linear regressions; the colored lines represent different PGLMM regressions conditional on each of the species random effects. (C) A regression of pairwise nucleotide diversity (π) on SNM rate (µ), fitted as a bivariate model in MCMCglmm for 102 species. The solid gray line indicates the model regression line; the dashed gray line indicates the expected slope for θ_π = 4N_eμ on the log scale. All axes are plotted on a log scale. PGLMM = phylogenetic generalized linear mixed model; SNM = single-nucleotide mutation.

Figure 4.

An analysis of short indel mutation rates for different species. The estimated mutation rates are presented on a log scale for clarity.

Figure 5.

The correlation between indel mutation rates and SNM rates plotted on a log scale with a 1:1 ratio shown as a dashed line (A). The aggregated log ratios of deletion/insertion in eukaryotes (B). SNM = single-nucleotide mutation.