mutation
Narasimhan VM, Rahbari R, Scally A, Wuster A, Mason D, Xue Y, Wright J, Trembath RC, Maher ER, van Heel DA, Auton A, Hurles ME, Tyler-Smith C & Durbin R 2017 Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes. Nat Commun 8:303.
- several approaches have been taken to estimating the human mutation rate, yielding results that differ substantially
- direct observation of mutations in present day parent–offspring comparisons (the direct rate)
- calibrating genetic divergence against fossil evidence for a past separation time (the phylogenetic rate)
- more recently, population-genetic approaches that effectively estimate the ratio of the mutation rate to the recombination rate
- for a genome-wide average mutation rate, the direct approaches have consistently estimated a rate of 1–1.25 × 10−8 per base pair (bp) per generation, significantly lower than phylogenetic estimates, which suggest around ~ 2 × 10−8 per bp per generation1 or estimates from population-genetic methods which suggest 1.6–1.7 × 10−8 per bp per generation
- measurements of the mutation rate in coding sequence, obtained via the direct method applied to exome sequences of trios, are widely scattered but typically higher than the genome-wide rate at around 1.25–2.1 × 10−8 per bp per generation
- the increase over genome-wide rates is usually attributed to differences in base composition giving higher frequencies of CpG dinucleotides
- possible shortcomings include:
- (c) consideration only of mutations occurring in a single generation, leading to incomplete ascertainment of post-zygotic mutations in parents or offspring
- (d) incomplete allowance for the correlation with paternal age
- (f) failure to account for gene conversion events
