Abstract

Mutations are the fundamental source of biological variation, and their rate is a crucial parameter for evolutionary and medical studies. Here we used whole-genome sequence data from 753 Icelandic males, grouped into 274 patrilines, to estimate the point mutation rate for 21.3 Mb of male-specific Y chromosome (MSY) sequence, on the basis of 1,365 meioses (47,123 years). The combined mutation rate for 15.2 Mb of X-degenerate (XDG), X-transposed (XTR) and ampliconic excluding palindromes (rAMP) sequence was 8.71 × 10−10 mutations per position per year (PPPY). We observed a lower rate (P = 0.04) of 7.37 × 10−10 PPPY for 6.1 Mb of sequence from palindromes (PAL), which was not statistically different from the rate of 7.2 × 10−10 PPPY for paternally transmitted autosomes1. We postulate that the difference between PAL and the other MSY regions may provide an indication of the rate at which nascent autosomal and PAL de novo mutations are repaired as a result of gene conversion.

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Acknowledgements

We thank E. Haraldsdóttir for help with processing some of the whole-genome sequencing data and K.S.H. Moore for help with calling SNP microarray genotypes. A.W.E. was funded by a grant from Rannís, Icelandic Student Research Fund (1103340061). A.J. was funded by the EUROTAST Marie Curie Framework Programme 7 Initial Training Network (290344).

Author information

Affiliations

  1. deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.

    • Agnar Helgason
    • , Axel W Einarsson
    • , Valdís B Guðmundsdóttir
    • , Ásgeir Sigurðsson
    • , Ellen D Gunnarsdóttir
    • , Anuradha Jagadeesan
    • , S Sunna Ebenesersdóttir
    • , Augustine Kong
    •  & Kári Stefánsson
  2. Department of Anthropology, University of Iceland, Reykjavik, Iceland.

    • Agnar Helgason
    • , Axel W Einarsson
    • , Anuradha Jagadeesan
    •  & S Sunna Ebenesersdóttir
  3. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Kári Stefánsson

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Contributions

A.H., A.W.E. and K.S. planned and directed the research. A.H. and A.W.E. analyzed the data, with A.K., V.B.G., E.D.G., A.J. and S.S.E. providing assistance with particular tasks. Á.S. performed the Sanger sequencing for the validation of de novo mutations. A.H., A.W.E. and K.S. wrote the manuscript.

Competing interests

A.H., V.B.G., A.S., E.D.G., A.K. and K.S. are employees of deCODE Genetics/Amgen.

Corresponding authors

Correspondence to Agnar Helgason or Kári Stefánsson.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1 and 2, Supplementary Tables 1, 5–7, 10 and 11, and Supplementary Note.

Excel files

  1. 1.

    Supplementary Table 2

    Summary of 739 branches in 274 patrilines with weighted sums of mutations.

  2. 2.

    Supplementary Table 3

    Summary of the 274 patrilines used in the study.

  3. 3.

    Supplementary Table 4

    Full list of 1,456 candidate de novo mutations at 2,050 positions with weights.

  4. 4.

    Supplementary Table 8

    Comparison of WGS and Illumina SNP chip genotypes.

  5. 5.

    Supplementary Table 9

    Mutation rate by haplogroup and sequence region for branches with XDG sequence depth >10×.

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DOI

https://doi.org/10.1038/ng.3171

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