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Cited by 77Evolution and Genetic DynamicsChromosomal and Genetic VariationsGenomics and Phylogenetic Studies

A model-based analysis of GC-biased gene conversion in the human and chimpanzee genomes

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Capra, John A., Hubisz, Melissa J., Kostka, Dennis, Pollard, Katherine S., Siepel, Adam·2013·PLoS Genetics
DOI 10.1371/journal.pgen.1003684PMC PMC3744432
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Abstract

GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available.

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  • GC-biased gene conversion (gBGC) is one of the factors that can increase local substitution rates across the genome and is often a confounding factor for the detection of adaptive evolution.

    “GC-biased gene conversion (gBGC) is one of the factors that can increase local substitution rates across the genome and is often a confounding factor for the detection of adaptive evolution (Duret and Galtier 2009; Kostka et al. 2012; Capra et al. 2013).”

    From Bayesian Detection of Convergent Rate Changes of Conserved Noncoding Elements on Phylogenetic Trees (2019) · cites this paper as Capra et al. 2013

    The Results (Probabilistic Model; no page given) state that gBGC increases W→S substitution rates, supporting the local-rate claim. The Results (Overlap with Fast-Evolving Sequences; no page given) report overlap between gBGC tracts and some genes identified as showing signatures of positive selection. This supports a potential confounding effect, but does not establish that gBGC often confounds the detection of adaptive evolution. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Capra, J. A., Hubisz, M. J., Kostka, D., Pollard, K. S., & Siepel, A.
Affiliations
  • Gladstone Institutes (US)
  • Cornell University (US)
  • University of Pittsburgh (US)
Corresponding author
  • Pollard, Katherine S.
  • Siepel, Adam
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2013-08-15
Volume
9
Issue
8
Pages
e1003684
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1003684
PMC
PMC3744432
OpenAlex
W1976720438
Cited by
77
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 9 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 13 · 2013: 1
FWCI
5.18
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • arXiv (Cornell University)
Funders
  • Pharmaceutical Research and Manufacturers of America Foundation
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM082901, #GM82901, R01GM102192, GM102192)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
GC-biased gene conversion, recombination, GC content variation, human-chimpanzee divergence, subtelomeric regions, recombination hotspots, primate genomes
MeSH terms
Animals, Base Sequence, Pan troglodytes, Chromosome Mapping, Gene Conversion, Humans, Mammals, Models, Theoretical, Phylogeny, Recombination, Genetic, Selection, Genetic, Sequence Alignment, Genome, Evolution, Molecular

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