The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Positive and Negative Selection on the Human Genome
Abstract
The distinction between deleterious, neutral, and adaptive mutations is a fundamental problem in the study of molecular evolution. Two significant quantities are the fraction of DNA variation in natural populations that is deleterious and destined to be eliminated and the fraction of fixed differences between species driven by positive Darwinian selection. We estimate these quantities using the large number of human genes for which there are polymorphism and divergence data. The fraction of amino acid mutations that is neutral is estimated to be 0.20 from the ratio of common amino acid (A) to synonymous (S) single nucleotide polymorphisms (SNPs) at frequencies of ≥ 15%. Among the 80% of amino acid mutations that are deleterious at least 20% of them are only slightly deleterious and often attain frequencies of 1–10%. We estimate that these slightly deleterious mutations comprise at least 3% of amino acid SNPs in the average individual or at least 300 per diploid genome. This estimate is not sensitive to human population history. The A/S ratio of fixed differences is greater than that of common SNPs and suggests that a large fraction of protein divergence is adaptive and driven by positive Darwinian selection.
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Citations
Cites
Hitchhiking Under Positive Darwinian Selection
Fay, J. C., & Wu, C.-I. (2000) · Genetics · doi:10.1093/genetics/155.3.1405 · Cited by 1,819
Self-citationMcVean, G. A. T., & Charlesworth, B. (2000) · Genetics · doi:10.1093/genetics/155.2.929 · Cited by 336
The costs of human inbreeding and their implications for variations at the DNA level.
Bittles, A. H., & Neel, J. V. (1994) · Nature Genetics · doi:10.1038/ng1094-117 · Cited by 311
Pattern of selective constraint in C. elegans and C. briggsae genomes
SHABALINA, S. A., & KONDRASHOV, A. S. (1999) · Genetical Research · doi:10.1017/s0016672399003821 · Cited by 94
Cited by
Initial sequence of the chimpanzee genome and comparison with the human genome
The Chimpanzee Sequencing and Analysis Consortium (2005) · Nature · doi:10.1038/nature04072 · Cited by 2,459
Identification of deleterious mutations within three human genomes
Chun, S., & Fay, J. C. (2009) · Genome Research · doi:10.1101/gr.092619.109 · Cited by 1,049
Self-citationInterrogating a High-Density SNP Map for Signatures of Natural Selection
Akey, J. M., Zhang, G., Zhang, K., Jin, L., & Shriver, M. D. (2002) · Genome Research · doi:10.1101/gr.631202 · Cited by 964
Inferring the molecular and phenotypic impact of amino acid variants with MutPred2
Pejaver, V., Urresti, J., Lugo-Martinez, J., Pagel, K. A., Lin, G. N., Nam, H.-J., Mort, M., Cooper, D. N., Sebat, J., Iakoucheva, L. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19669-x · Cited by 923
Accounting for Human Polymorphisms Predicted to Affect Protein Function
Ng, P. C., & Henikoff, S. (2002) · Genome Research · doi:10.1101/gr.212802 · Cited by 699
Metadata
- Authors
- Fay, J. C., Wyckoff, G. J., & Wu, C.-I.
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-07-01
- Volume
- 158
- Issue
- 3
- Pages
- 1227-1234
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2160714946
- Cited by
- 646
- References
- 4
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- closed
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