A population threshold for functional polymorphisms

• Published in: Genome research 2003-08, Vol.13 (8), p.1873-1879
• Main Authors: Wong, Gane Ka-Shu, Yang, Zhiyong, Passey, Douglas A, Kibukawa, Miho, Paddock, Marcia, Liu, Chun-Rong, Bolund, Lars, Yu, Jun
• Format: Article
• Language: English
• Subjects: Animals; Computational Biology - statistics & numerical data; Databases, Genetic - statistics & numerical data; Gene Frequency - genetics; Genetic Variation - genetics; Genetics, Population - methods; Genetics, Population - statistics & numerical data; Gorilla gorilla; Humans; Letters; Pan troglodytes; Polymorphism, Genetic - genetics; Polymorphism, Genetic - physiology; Polymorphism, Single Nucleotide - genetics; Polymorphism, Single Nucleotide - physiology; Selection, Genetic
• ISSN: 1088-9051; 1054-9803
• DOI: 10.1101/gr.1324303

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 approximately 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 7000 approximately 17000 years.