Direct estimate of the rate of germline mutation in a bird

Abstract

The fidelity of DNA replication together with repair mechanisms ensure that the genetic material is properly copied from one generation to another. However, on extremely rare occasions when damages to DNA or replication errors are not repaired, germline mutations can be transmitted to the next generation. Because of the rarity of these events, studying the rate at which new mutations arise across organisms has been a great challenge, especially in multicellular nonmodel organisms with large genomes. We sequenced the genomes of 11 birds from a three-generation pedigree of the collared flycatcher (Ficedula albicollis) and used highly stringent bioinformatic criteria for mutation detection and used several procedures to validate mutations, including following the stable inheritance of new mutations to subsequent generations. We identified 55 de novo mutations with a 10-fold enrichment of mutations at CpG sites and with only a modest male mutation bias. The estimated rate of mutation per site per generation was 4.6 × 10−9, which corresponds to 2.3 × 10−9 mutations per site per year. Compared to mammals, this is similar to mouse but about half of that reported for humans, which may be due to the higher frequency of male mutations in humans. We confirm that mutation rate scales positively with genome size and that there is a strong negative relationship between mutation rate and effective population size, in line with the drift-barrier hypothesis. Our study illustrates that it should be feasible to obtain direct estimates of the rate of mutation in essentially any organism from which family material can be obtained.

Inferring Individual Inbreeding and Demographic History from Segments of Identity by Descent inFicedulaFlycatcher Genome Sequences

“…We simulated constant N e = 100,000 (Nadachowska-Brzyska et al 2016), and mutation rate (m) = 5 3 10 29 per base pair per generation (Ellegren 2007;Smeds et al 2016) on a single 50-Mb chromosome with variable recombination rate along its length. We set recombination rates that were representative of the spectrum of recombination rates in the collared flycatcher genome, ranging from 1 to 20 cM/Mb in 10-Mb blocks along the length of the simulated chromosome.…”

Causes and evolutionary consequences of primordial germ-cell specification mode in metazoans

“…We note that recent dN/dS data suggests that innate mutation rate variation between frog (inheritance) and salamander (induction) lineages likely explains fast evolution in the former group (113), and not a broad release of constraint in frogs (as dN/dS was similar among taxa), as had been claimed for these taxa (using dN alone) under the PGCspecification hypothesis (20). Direct measures of the mutation rate within a generation (110) and per unit time, combined with multifactorial assessments, will help further discern whether and how PGC specification mode per se influences mutation rates in those taxa. To better understand whether PGC-specification mode influences cell-cell selection on mutations in the germ-line lineage in metazoans, future studies should also assess the evolution of genes specifically expressed in pre-PGC (and post-PGC) cells to measure the effects of selection (such as dN/dS; ref.…”

“…Furthermore, even if PGC-specification mode shapes mutation rates before or during PGC stages, depending on the strength of effect, it might not be strongly correlated to mutation rates across species, because this value also depends on numbers of mutations (and cell divisions) arising after PGCs are specified (110). Furthermore, mutation rates may vary with other factors such as metabolic rates (111), individual age (112), and natural selection on mutation rates, which depends on population size (102).…”

“…Recent direct estimates of mutation rates using whole-genome DNA sequencing indicate a lower rate in the bird Ficedula albicollis (inheritance) than humans and chimpanzees (induction) (see ref. 110 for additional taxa such as mouse). A lower mutation rate may be selectively advantageous (101,102), and thus speculatively might sometimes contribute toward the evolution of inheritance mode in animals.…”

Variable Autosomal and X Divergence Near and Far from Genes Affects Estimates of Male Mutation Bias in Great Apes

“…Male mutation bias is observed across mammals (Li et al 2002; Taylor et al 2006; Wilson Sayres et al 2011), birds (Axelsson et al 2004; Smeds et al 2016), fish (Ellegren and Fridolfsson 2003), and flies (Bachtrog 2008). In mammals, the magnitude of α varies tremendously, and is predominantly explained by variation in generation time across species (Wilson Sayres et al 2011).…”