Genomic regions exhibiting positive selection identified from dense genotype data

• Published in: Genome research Vol. 15; no. 11; pp. 1553 - 1565
• Main Authors: Carlson, Christopher S., Thomas, Daryl J., Eberle, Michael A., Swanson, Johanna E., Livingston, Robert J., Rieder, Mark J., Nickerson, Deborah A.
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.11.2005
• Subjects: Asian - genetics; Base Sequence; Black or African American - genetics; DNA Primers; Evolution, Molecular; Gene Frequency; Genes - genetics; Genome, Human - genetics; Genomics - methods; Genotype; Humans; Letters; Molecular Sequence Data; Polymorphism, Genetic; Selection, Genetic; Sequence Analysis, DNA; White People - genetics
• ISSN: 1088-9051; 1549-5469
• DOI: 10.1101/gr.4326505

The allele frequency spectrum of polymorphisms in DNA sequences can be used to test for signatures of natural selection that depart from the expected frequency spectrum under the neutral theory. We observed a significant ( P = 0.001) correlation between the Tajima's D test statistic in full resequencing data and Tajima's D in a dense, genome-wide data set of genotyped polymorphisms for a set of 179 genes. Based on this, we used a sliding window analysis of Tajima's D across the human genome to identify regions putatively subject to strong, recent, selective sweeps. This survey identified seven Contiguous Regions of Tajima's D Reduction (CRTRs) in an African-descent population (AD), 23 in a European-descent population (ED), and 29 in a Chinese-descent population (XD). Only four CRTRs overlapped between populations: three between ED and XD and one between AD and ED. Full resequencing of eight genes within six CRTRs demonstrated frequency spectra inconsistent with neutral expectations for at least one gene within each CRTR. Identification of the functional polymorphism (and/or haplotype) responsible for the selective sweeps within each CRTR may provide interesting insights into the strongest selective pressures experienced by the human genome over recent evolutionary history.