Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy

Polley Shamik; Louzada Sandra; Forni DiegoSironi ManuelaBalaskas TheodosiusHains David S.Yang FengtangHollox Edward J.

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Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy

机译：Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy

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The dietary change resulting from the domestication of plant and animal species and development of agriculture at different locations across the world was one of the most significant changes in human evolution. An increase in dietary carbohydrates caused an increase in dental caries following the development of agriculture, mediated by the cariogenic oral bacterium Streptococcus mutans. Salivary agglutinin SAG, encoded by the deleted in malignant brain tumors 1 (DMBT1) gene is an innate immune receptor glycoprotein that binds a variety of bacteria and viruses, and mediates attachment of S. mutans to hydroxyapatite on the surface of the tooth. In this study we show that multiallelic copy number variation (CNV) within DMBT1 is extensive across all populations and is predicted to result in between 7-20 scavenger-receptor cysteine-rich (SRCR) domains within each SAG molecule. Direct observation of de novo mutation in multigeneration families suggests these CNVs have a very high mutation rate for a protein-coding locus, with a mutation rate of up to 5 per gamete. Given that the SRCR domains bind S. mutans and hydroxyapatite in the tooth, we investigated the association of sequence diversity at the SAG-binding gene of S. mutans, and DMBT1 CNV. Furthermore, we show that DMBT1 CNV is also associated with a history of agriculture across global populations, suggesting that dietary change as a result of agriculture has shaped the pattern of CNV at DMBT1, and that the DMBT1-S. mutans interaction is a promising model of host-pathogen-culture coevolution in humans.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第16期|5105-5110|共6页
作者
Polley Shamik; Louzada Sandra; Forni DiegoSironi ManuelaBalaskas TheodosiusHains David S.Yang FengtangHollox Edward J.;
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作者单位

Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England;

Sci Inst IRCCS E Medea, Bioinformat, I-23842 Bosisio Parini, Italy;

Univ Tennessee, Hlth Sci Ctr, Le Bonheur Childrens Hosp, Div Pediat Nephrol, Memphis, TN 38103 USAWellcome Trust Sanger Inst, Mol Cytogenet Facil, Cambridge CB10 1SA, England;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
copy number variation; agriculture; DMBT1; mutation; structural variation;

Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy

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