Genomic regions exhibiting positive selection identified from dense genotype data
Open accessAbstract
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.
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SLC30A9 encodes ZnT9, a ubiquitously expressed zinc transporter, and has been repeatedly reported as a top candidate region for positive selection in humans, mostly in East Asian populations.
“The SLC30A9 gene (chr4: 41,990,502–42,090,461; GRCh38) has been repeatedly reported as a top candidate region for positive selection in several genome-wide scans of selection, mostly in East Asian populations [14,16–20].”
From Human genetic adaptation related to cellular zinc homeostasis (2023) · cites this paper as [16]
The Results and Screening for positive selection sections describe candidate regions in several populations, including a Chinese-descent population, but the retrieved passages do not identify SLC30A9 as one of them. Searches for SLC30A9, ZnT9, and the stated chromosome 4 location found no passage linking this gene to positive selection; this copy therefore does not establish the claim for this citation. (LLM, conf=0.73)
Experimental — accuracy not yet measuredPrevious studies detected strong signatures of positive selection in the SLC30A9 region.
“The motivation for this study was the previous detection of strong signatures of positive selection in the SLC30A9 region [13,14,16,17,20,25].”
From Human genetic adaptation related to cellular zinc homeostasis (2023) · cites this paper as [16]
The Results and Screening for positive selection sections report candidate regions with signatures of selection, but the passages found do not identify SLC30A9 or link its region to one of those signals. Searches for SLC30A9 and zinc-transporter terminology found no passage addressing the specific claim. (LLM, conf=0.76)
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- Authors
- Carlson, C. S., Thomas, D. J., Eberle, M. A., Swanson, J. E., Livingston, R. J., Rieder, M. J., & Nickerson, D. A.
- Affiliations
- University of Washington (US)
- University of California, Santa Cruz (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-10-26
- Volume
- 15
- Issue
- 11
- Pages
- 1553-1565
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC1310643
- OpenAlex
- W2037710951
- Cited by
- 298
- References
- 51
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 11 · 2023: 12 · 2022: 7 · 2021: 10 · 2020: 15 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 10 · 2015: 11 · 2014: 16 · 2013: 11 · 2012: 12
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 66682, HL66642, U01HL066682, U01HL066642)
- National Human Genome Research Institute (IP41HG02371, HG 02238, P41HG002371, R01HG002238)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- positive selection, selective sweeps, Tajima's D, allele frequency spectrum, human genome, genetic differentiation, African descent populations, resequencing, functional polymorphisms
- MeSH terms
- Asian, Base Sequence, Black or African American, Gene Frequency, Genes, Genotype, Humans, Molecular Sequence Data, Polymorphism, Genetic, Selection, Genetic, Genome, Human, Sequence Analysis, DNA, DNA Primers, Evolution, Molecular, Genomics, White People
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