Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The Y-chromosome point mutation rate in humans


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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A de novo mutation at MSY position 7,270,276 in the largest patriline used in this study.
Figure 2: The number of mutations by branch length and calendar year.

Similar content being viewed by others


  1. Kong, A. et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488, 471–475 (2012).

    Article  CAS  Google Scholar 

  2. Conrad, D.F. et al. Variation in genome-wide mutation rates within and between human families. Nat. Genet. 43, 712–714 (2011).

    Article  CAS  Google Scholar 

  3. Michaelson, J.J. et al. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell 151, 1431–1442 (2012).

    Article  CAS  Google Scholar 

  4. Roach, J.C. et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328, 636–639 (2010).

    Article  CAS  Google Scholar 

  5. Sun, J.X. et al. A direct characterization of human mutation based on microsatellites. Nat. Genet. 44, 1161–1165 (2012).

    Article  CAS  Google Scholar 

  6. Campbell, C.D. et al. Estimating the human mutation rate using autozygosity in a founder population. Nat. Genet. 44, 1277–1281 (2012).

    Article  CAS  Google Scholar 

  7. Skaletsky, H. et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423, 825–837 (2003).

    Article  CAS  Google Scholar 

  8. Hallast, P., Balaresque, P., Bowden, G.R., Ballereau, S. & Jobling, M.A. Recombination dynamics of a human Y-chromosomal palindrome: rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions. PLoS Genet. 9, e1003666 (2013).

    Article  CAS  Google Scholar 

  9. Rozen, S. et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423, 873–876 (2003).

    Article  CAS  Google Scholar 

  10. Heyer, E., Puymirat, J., Dieltjes, P., Bakker, E. & de Knijff, P. Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees. Hum. Mol. Genet. 6, 799–803 (1997).

    Article  CAS  Google Scholar 

  11. Xue, Y. et al. Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree. Curr. Biol. 19, 1453–1457 (2009).

    Article  CAS  Google Scholar 

  12. Poznik, G.D. et al. Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science 341, 562–565 (2013).

    Article  CAS  Google Scholar 

  13. Francalacci, P. et al. Low-pass DNA sequencing of 1200 Sardinians reconstructs European Y-chromosome phylogeny. Science 341, 565–569 (2013).

    Article  CAS  Google Scholar 

  14. Scozzari, R. et al. An unbiased resource of novel SNP markers provides a new chronology for the human Y chromosome and reveals a deep phylogenetic structure in Africa. Genome Res. 24, 535–544 (2014).

    Article  CAS  Google Scholar 

  15. Schrider, D.R., Hourmozdi, J.N. & Hahn, M.W. Pervasive multinucleotide mutational events in eukaryotes. Curr. Biol. 21, 1051–1054 (2011).

    Article  CAS  Google Scholar 

  16. Ballantyne, K.N. et al. Mutability of Y-chromosomal microsatellites: rates, characteristics, molecular bases, and forensic implications. Am. J. Hum. Genet. 87, 341–353 (2010).

    Article  CAS  Google Scholar 

  17. Cruciani, F. et al. A revised root for the human Y chromosomal phylogenetic tree: the origin of patrilineal diversity in Africa. Am. J. Hum. Genet. 88, 814–818 (2011).

    Article  CAS  Google Scholar 

  18. Elhaik, E., Tatarinova, T.V., Klyosov, A.A. & Graur, D. The 'extremely ancient' chromosome that isn't: a forensic bioinformatic investigation of Albert Perry's X-degenerate portion of the Y chromosome. Eur. J. Hum. Genet. 22, 1111–1116 (2014).

    Article  CAS  Google Scholar 

  19. Mendez, F.L. et al. An African American paternal lineage adds an extremely ancient root to the human Y chromosome phylogenetic tree. Am. J. Hum. Genet. 92, 454–459 (2013).

    Article  CAS  Google Scholar 

  20. Scally, A. & Durbin, R. Revising the human mutation rate: implications for understanding human evolution. Nat. Rev. Genet. 13, 745–753 (2012).

    Article  CAS  Google Scholar 

  21. Walsh, B. Estimating the time to the most recent common ancestor for the Y chromosome or mitochondrial DNA for a pair of individuals. Genetics 158, 897–912 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Behar, D.M. et al. A “Copernican” reassessment of the human mitochondrial DNA tree from its root. Am. J. Hum. Genet. 90, 675–684 (2012).

    Article  CAS  Google Scholar 

  23. Ingman, M., Kaessmann, H., Paabo, S. & Gyllensten, U. Mitochondrial genome variation and the origin of modern humans. Nature 408, 708–713 (2000).

    Article  CAS  Google Scholar 

  24. McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 26, 2069–2070 (2010).

    Article  CAS  Google Scholar 

  25. Rosser, Z.H., Balaresque, P. & Jobling, M.A. Gene conversion between the X chromosome and the male-specific region of the Y chromosome at a translocation hotspot. Am. J. Hum. Genet. 85, 130–134 (2009).

    Article  CAS  Google Scholar 

  26. Trombetta, B., Cruciani, F., Underhill, P.A., Sellitto, D. & Scozzari, R. Footprints of X-to-Y gene conversion in recent human evolution. Mol. Biol. Evol. 27, 714–725 (2010).

    Article  CAS  Google Scholar 

  27. Trombetta, B., Sellitto, D., Scozzari, R. & Cruciani, F. Inter- and intraspecies phylogenetic analyses reveal extensive X-Y gene conversion in the evolution of gametologous sequences of human sex chromosomes. Mol. Biol. Evol. 31, 2108–2123 (2014).

    Article  CAS  Google Scholar 

  28. Gudbjartsson, D.F. et al. Sequence variants from whole genome sequencing a large group of Icelanders. Sci. Data (in the press).

  29. Martin, E.R. et al. SeqEM: an adaptive genotype-calling approach for next-generation sequencing studies. Bioinformatics 26, 2803–2810 (2010).

    Article  CAS  Google Scholar 

  30. Harris, R.S. Improved Pairwise Alignment of Genomic DNA. PhD thesis. Penn. State Univ. (2007).

  31. Repping, S. et al. High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat. Genet. 38, 463–467 (2006).

    Article  CAS  Google Scholar 

Download references


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

Authors and Affiliations



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.

Corresponding authors

Correspondence to Agnar Helgason or Kári Stefánsson.

Ethics declarations

Competing interests

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

Integrated supplementary information

Supplementary Figure 1 An example of a de novo mutation at paralogous positions.

We examine a G>A de novo mutation in the largest patriline with 86 meioses (the same patriline shown in Fig. 1), where sequence reads with the mutation map to three paralogous positions that are flanked by identical sequence in the human reference genome (NCBI b36), each shown in a separate depiction of the patriline: (a) 23,235,573 (rAMP7), (b) 24,071,677 (PAL1 arm 1), (c) 26,710,008 (PAL1 arm 2) and (d) with all reads combined (adjusting for the reverse complement orientation of reads at position 24,071,677 relative to positions 23,235,573 and 26,710,008). The allele state of the human reference sequence is indicated after the text "ref." Each square represents a male in the patriline, with vertical position scaled by birth year and the lines between squares representing Y-chromosome transmission events. The filled squares represent males demarcating the branches to which mutations can be assigned. Males with WGS data are indicated underneath a subset of filled squares by counts of alleles mapped to forward and reverse strands at the shown position(s) and inside each such square is the genotype called on the basis of these alleles. When examined separately, the genotypes called for the WGS males at the three positions provide inconsistent results about the branch on which the mutation occurred and the number of mutations required to account for the distribution of genotypes in the patriline. However, when the genotypes at all three positions are combined (d), it becomes clear that a single G>A mutation occurred on the branch labeled with the mutation event. We note, however, that it is not possible to resolve at which of the three positions the mutation occurred. Thus, for the purposes of this mutation rate study, each of the three paralogous positions was assigned one-third of a mutation, i.e., a weight of 1/3.

Supplementary Figure 2 The XDG normalized sequence depth of branches by sequence region and haplogroup.

Results are shown for the 482 branches with an average XDG sequence depth >10×. For each branch, the average depth in each of 27 regions of the 4 sequence classes was normalized through division by its average XDG sequence depth. This was done because the branches have very different baseline expectations of sequence depth, which depend on the number of males who belong to them and the amount of sequencing undertaken for each. Normalization by average XDG sequence depth allows meaningful comparison of sequence depth among branches. Moreover, as the XDG region is mostly present in single copy, the normalized value provides some information about the relative magnitude of change in copy number. For each sequence region and haplogroup, we then calculated and plotted the average XDG normalized sequence depth with 95% confidence intervals. The greatest differences are seen for region PAL_IR2. Here we see that males belonging to haplogroup Q1a3a appear to have just a single copy of each orientation of IR2 (around 70 and 80 kb in length, respectively), as seen in the NCBI Build 36 reference sequence, whereas males from the other haplogroups have an excess of 17–30% of reads that map to these small sequence regions, indicating a greater copy number of at least part of the IR2 sequence. Other regions that exhibit differences between haplogroups are rAMP2, where the XDG normalized sequence depth is greater in E1b1 and Q1a3a than in the other haplogroups, and XTR2, where R1b1a and Q1a3a exhibit greater XDG normalized sequence depth than the rest. For most other sequence regions, there is little evidence for differences in copy number among haplogroups. On the basis of this evidence, we deem it unlikely that our mutation rate estimates are affected by copy number variation of MSY sequence.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1 and 2, Supplementary Tables 1, 5–7, 10 and 11, and Supplementary Note. (PDF 656 kb)

Supplementary Table 2

Summary of 739 branches in 274 patrilines with weighted sums of mutations. (XLSX 98 kb)

Supplementary Table 3

Summary of the 274 patrilines used in the study. (XLSX 13 kb)

Supplementary Table 4

Full list of 1,456 candidate de novo mutations at 2,050 positions with weights. (XLSX 258 kb)

Supplementary Table 8

Comparison of WGS and Illumina SNP chip genotypes. (XLSX 34 kb)

Supplementary Table 9

Mutation rate by haplogroup and sequence region for branches with XDG sequence depth >10×. (XLSX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Helgason, A., Einarsson, A., Guðmundsdóttir, V. et al. The Y-chromosome point mutation rate in humans. Nat Genet 47, 453–457 (2015).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing