Differences in the rare variant spectrum among human populations.
Mutations occur at vastly different rates across the genome, and populations, leading to differences in the spectrum of segregating polymorphisms. Here, we investigate variation in the rare variant spectrum in a sample of human genomes representing all major world populations. We find at least two d...
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Public Library of Science (PLoS)
2017-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006581&type=printable |
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| author | Iain Mathieson David Reich |
| author_facet | Iain Mathieson David Reich |
| author_sort | Iain Mathieson |
| collection | DOAJ |
| description | Mutations occur at vastly different rates across the genome, and populations, leading to differences in the spectrum of segregating polymorphisms. Here, we investigate variation in the rare variant spectrum in a sample of human genomes representing all major world populations. We find at least two distinct signatures of variation. One, consistent with a previously reported signature is characterized by an increased rate of TCC>TTC mutations in people from Western Eurasia and South Asia, likely related to differences in the rate, or efficiency of repair, of damage due to deamination of methylated guanine. We describe the geographic extent of this signature and show that it is detectable in the genomes of ancient, but not archaic humans. The second signature is private to certain Native American populations, and is concentrated at CpG sites. We show that this signature is not driven by differences in the CpG mutation rate, but is a result of the fact that highly mutable CpG sites are more likely to undergo multiple independent mutations across human populations, and the spectrum of such mutations is highly sensitive to recent demography. Both of these effects dramatically affect the spectrum of rare variants across human populations, and should be taken into account when using mutational clocks to make inference about demography. |
| format | Article |
| id | doaj-art-d7642a3485ad4f43911cf4e4813235fe |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2017-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-d7642a3485ad4f43911cf4e4813235fe2025-08-20T03:11:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-02-01132e100658110.1371/journal.pgen.1006581Differences in the rare variant spectrum among human populations.Iain MathiesonDavid ReichMutations occur at vastly different rates across the genome, and populations, leading to differences in the spectrum of segregating polymorphisms. Here, we investigate variation in the rare variant spectrum in a sample of human genomes representing all major world populations. We find at least two distinct signatures of variation. One, consistent with a previously reported signature is characterized by an increased rate of TCC>TTC mutations in people from Western Eurasia and South Asia, likely related to differences in the rate, or efficiency of repair, of damage due to deamination of methylated guanine. We describe the geographic extent of this signature and show that it is detectable in the genomes of ancient, but not archaic humans. The second signature is private to certain Native American populations, and is concentrated at CpG sites. We show that this signature is not driven by differences in the CpG mutation rate, but is a result of the fact that highly mutable CpG sites are more likely to undergo multiple independent mutations across human populations, and the spectrum of such mutations is highly sensitive to recent demography. Both of these effects dramatically affect the spectrum of rare variants across human populations, and should be taken into account when using mutational clocks to make inference about demography.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006581&type=printable |
| spellingShingle | Iain Mathieson David Reich Differences in the rare variant spectrum among human populations. PLoS Genetics |
| title | Differences in the rare variant spectrum among human populations. |
| title_full | Differences in the rare variant spectrum among human populations. |
| title_fullStr | Differences in the rare variant spectrum among human populations. |
| title_full_unstemmed | Differences in the rare variant spectrum among human populations. |
| title_short | Differences in the rare variant spectrum among human populations. |
| title_sort | differences in the rare variant spectrum among human populations |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006581&type=printable |
| work_keys_str_mv | AT iainmathieson differencesintherarevariantspectrumamonghumanpopulations AT davidreich differencesintherarevariantspectrumamonghumanpopulations |