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Older males beget more mutations

Nature Genetics volume 44, pages 1174–1176 (2012)Cite this article

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Three papers characterizing human germline mutation rates bolster evidence for a relatively low rate of base substitution in modern humans and highlight a central role for paternal age in determining rates of mutation. These studies represent the advent of a transformation in our understanding of mutation rates and processes, which may ultimately have public health implications.

Under the collective banner of DNA sequence mutation lie a handful of different mutational processes, each of which can be linked to a fundamental cellular process, such as DNA replication, repair or recombination. The mutational process that is dominant in terms of the number of new alleles introduced each generation is base substitution, with an average rate on the order of 1 mutation for every 100 million bases. By contrast, replication slippage at simple tandem repeats occurs at rates that are four to five orders of magnitude higher. Three recent papers1,2,3, including one by Campbell et al.1 on page 1277 of this issue, report estimates of the human germline sequence mutation rate, each making use of improved cost-effective genome sequencing technologies but taking different approaches.

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Figure 1: Comparing the birth prevalence of developmental disorders caused by maternal chromosomal aneuploidies and paternal de novo base substitutions.

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  1. Matthew Hurles is at the The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.,

    Matthew Hurles

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Correspondence to Matthew Hurles.

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Hurles, M. Older males beget more mutations. Nat Genet 44, 1174–1176 (2012). https://doi.org/10.1038/ng.2448

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