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

Shamik Polley, Sandra Louzada, Diego Forni, Manuela Sironi, Theodosius Balaskas, David Hains, Fengtang Yang, Edward J. Hollox

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)5105-5110
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number16
DOIs
StatePublished - Apr 21 2015

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Agglutinins
Streptococcus mutans
Brain Neoplasms
Agriculture
Population
Genes
Scavenger Receptors
Mutation Rate
Durapatite
Cysteine
Tooth
Dietary Carbohydrates
Bacteria
Virus Attachment
Dental Caries
Germ Cells
Glycoproteins
Observation
Mutation
Proteins

All Science Journal Classification (ASJC) codes

  • General

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Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy. / Polley, Shamik; Louzada, Sandra; Forni, Diego; Sironi, Manuela; Balaskas, Theodosius; Hains, David; Yang, Fengtang; Hollox, Edward J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 16, 21.04.2015, p. 5105-5110.

Research output: Contribution to journalArticle

Polley, Shamik ; Louzada, Sandra ; Forni, Diego ; Sironi, Manuela ; Balaskas, Theodosius ; Hains, David ; Yang, Fengtang ; Hollox, Edward J. / Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 16. pp. 5105-5110.
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