A Population Threshold for Functional Polymorphisms
- Gane Ka-Shu Wong1,2,3,6,
- Zhiyong Yang4,
- Douglas A. Passey1,
- Miho Kibukawa1,
- Marcia Paddock1,
- Chun-Rong Liu1,
- Lars Bolund1,3,5, and
- Jun Yu1,2,3,6
- 1 University of Washington Genome Center, Department of Medicine, Seattle, Washington 98195, USA
- 2 James Watson Institute of Zhejiang University, Hangzhou Genomics Institute, Key Laboratory of Bioinformatics of Zhejiang Province, Hangzhou 310007, China
- 3 Beijing Institute of Genomics, Center of Genomics and Bioinformatics, Chinese Academy of Sciences, Beijing 101300, China
- 4 Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
- 5 The Institute of Human Genetics, University of Aarhus, DK-8000 Århus C, Denmark
Abstract
We sequenced 114 genes (for DNA repair, cell cycle arrest, apoptosis, and detoxification)in a mixed human population and observed a sudden increase in the number of functional polymorphisms below a minor allele frequency of ∼6%. Functionality is assessed by considering the ratio in the number of nonsynonymous single nucletide polymorphisms (SNPs)to the number of synonymous or intron SNPs. This ratio is steady from below 1% in frequency—that regime traditionally associated with rare Mendelian diseases—all the way up to about 6% in frequency, after which it falls precipitously. We consider possible explanations for this threshold effect. There are four candidates as follows: (1)deleterious variants that have yet to be purified from the population, (2)balancing selection, in which a selective advantage accrues to the heterozygotes, (3)population-specific functional polymorphisms, and (4)adaptive variants that are accumulating in the population as a response to the dramatic environmental changes of the last 7,000∼17,000 years.
Footnotes
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Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1324303.
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↵6 Corresponding authors. E-MAIL gksw{at}u.washington.edu; FAX (206)685-7344. E-MAIL junyu{at}u.washington.edu; FAX (206)685-7344.
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- Accepted June 4, 2003.
- Received March 7, 2003.
- Cold Spring Harbor Laboratory Press
