mutation
Harris K & Prichard JK 2017 Rapid evolution of the human mutation spectrum. eLife 6:e24284.
- shifts in generation time or other life-history traits may affect mutational spectra, particularly for CpG transitions
- most CpG transitions result from spontaneous methyl-cytosine deamination as opposed to errors in DNA replication
- Europeans have a lower fraction of CpG variants compared to Africans, East Asians and South Asians (Figure 1B), consistent with a recent report of a lower rate of de novo CCG→CTG mutations in European individuals compared to Pakistanis (Narasimhan et al., 2016)
- such a pattern may be consistent with a shorter average generation time in Europeans
- it is unclear that a plausible shift in generation-time could produce such a large effect
- the other patterns evident in Figure 1 do not seem explainable by known processes
- mutational spectra differ significantly among closely related human populations
- they differ greatly among the great ape species
- subtle, concerted shifts in the frequencies of many different mutation types are more widespread than dramatic jumps in the rate of single mutation types
- the existence of the European TCC→TTC pulse shows that both modes of evolution do occur
- it seems parsimonious to us to propose that most of this variation is driven by the appearance and drift of genetic modifiers of mutation rate
