| Evolution of detoxifying systems: the role of environment and population history in shaping genetic diversity at human CYP2D6 locus. | |
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MedLine Citation:
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PMID: 20520586 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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OBJECTIVE: The transition from food collection to food production (FP) modified the nature of selective pressures, and several studies illustrate that genetic adaptation to new lifestyle has occurred in humans since the agricultural revolution. Here we test the hypothesis that high levels of genetic variation at CYP2D6, a locus coding for a detoxifying enzyme of the cytochrome P450 complex, reflect this change. METHODS: We compared DNA sequences and predicted the levels of enzyme activity across 10 African, Asian and European populations, six of which currently rely on hunting and gathering (HG) while four on food production (FP). RESULTS AND CONCLUSION: HG and FP showed similar levels of CYP2D6 diversity, but displayed different substitution patterns at coding DNA sites possibly related to selective differences. Comparison with variation at presumably neutral independent loci confirmed this finding, despite the confounding effects of population history, resulting in higher overall variation in Africans than in Eurasians. The differences between HG and FP populations suggest that new lifestyle and dietary habits acquired in the transition to agriculture affected the variation pattern at CYP2D6, leading to an increase in FP populations of the frequency of alleles that are associated with a slower rate of metabolism. These alleles reached a balanced co-existence with other important and previously selected variants. We suggest that the pronounced substrate-dependent activity of most of these enzymes expanded the spectrum of the metabolic response. |
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Authors:
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Silvia Fuselli; Cesare de Filippo; Stefano Mona; Johanna Sistonen; Piero Fariselli; Giovanni Destro-Bisol; Guido Barbujani; Giorgio Bertorelle; Antti Sajantila |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmacogenetics and genomics Volume: 20 ISSN: 1744-6880 ISO Abbreviation: Pharmacogenet. Genomics Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101231005 Medline TA: Pharmacogenet Genomics Country: United States |
Other Details:
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Languages: eng Pagination: 485-99 Citation Subset: IM |
Affiliation:
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Department of Biology and Evolution, University of Ferrara, Ferrara, Italy. silvia.fuselli@unife.it |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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