Quantification of GC-biased gene conversion in the human genome

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Glemin, SylvainUppsala universitet,Växtekologi och evolution (author)

Quantification of GC-biased gene conversion in the human genome

Article/chapterEnglish2015

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2015-05-20
Cold Spring Harbor Laboratory,2015
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LIBRIS-ID:oai:DiVA.org:uu-261253
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-261253URI
https://doi.org/10.1101/gr.185488.114DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact on the evolution of mammalian genomes. However, a detailed quantification of the process is still lacking. The strength of gBGC can be measured from the analysis of derived allele frequency spectra (DAF), but this approach is sensitive to a number of confounding factors. In particular, we show by simulations that the inference is pervasively affected by polymorphism polarization errors and by spatial heterogeneity in gBGC strength. We propose a new general method to quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial heterogeneity into account, and jointly estimating mutation bias. Applying it to human polymorphism data from the 1000 Genomes Project, we show that the strength of gBGC does not differ between hypermutable CpG sites and non-CpG sites, suggesting that in humans gBGC is not caused by the base-excision repair machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area. However, given that recombination occurs primarily within recombination hotspots, 1%-2% of the human genome is subject to strong gBGC. On average, gBGC is stronger in African than in non-African populations, reflecting differences in effective population sizes. However, due to more heterogeneous recombination landscapes, the fraction of the genome affected by strong gBGC is larger in non-African than in African populations. Given that the location of recombination hotspots evolves very rapidly, our analysis predicts that, in the long term, a large fraction of the genome is affected by short episodes of strong gBGC.

Subject headings and genre

NATURVETENSKAP Biologi Genetik hsv//swe
NATURAL SCIENCES Biological Sciences Genetics hsv//eng
NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng

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Arndt, Peter F. (author)
Messer, Philipp W. (author)
Petrov, Dmitri (author)
Galtier, Nicolas (author)
Duret, Laurent (author)
Uppsala universitetVäxtekologi och evolution (creator_code:org_t)

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In:Genome Research: Cold Spring Harbor Laboratory25:8, s. 1215-12281088-90511549-5469

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By the author/editor: Glemin, Sylvain; Arndt, Peter F.; Messer, Philipp ...; Petrov, Dmitri; Galtier, Nicolas; Duret, Laurent

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Genetics

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

Articles in the publication: Genome Research

By the university: Uppsala University

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