ArticleProceedings of the National Academy of Sciences of the United States of America2015
Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Serotype and distribution of adhesion genes in Streptococcus mutans isolated from people with Parkinson's disease.Odontology · 2025Article
- Salivary Th17 cytokine, human β-defensin 1-3, and salivary scavenger and agglutinin levels in Crohn's disease.Clinical oral investigations · 2024Article
- High-Resolution FISH Analysis Using DNA Fibers Generated by Molecular Combing.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A Catalog of Coding Sequence Variations in Salivary Proteins' Genes Occurring during Recent Human Evolution.International journal of molecular sciences · 2023Article
- Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity.Nature communications · 2023Article
- Balancing selection at the human salivary agglutinin gene (iScience · 2022Article
- Systems biology approach to functionally assess theProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Similarity-Based Analysis of Allele Frequency Distribution among Multiple Populations Identifies Adaptive Genomic Structural Variants.Molecular biology and evolution · 2022Article
- Deleted in malignant brain tumor 1 genetic variation confers urinary tract infection risk in children and mice.Clinical and translational medicine · 2021Article
- Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.The Journal of experimental medicine · 2021Article
- Review
- Human and Nonhuman Primate Lineage-Specific Footprints in the Salivary Proteome.Molecular biology and evolution · 2020Article
- The Driver of Extreme Human-Specific Olduvai Repeat Expansion Remains Highly Active in the Human Genome.Genetics · 2020Article
- An Evolutionary Perspective on the Impact of Genomic Copy Number Variation on Human Health.Journal of molecular evolution · 2020Review
- DMBT1 inhibition of Pseudomonas aeruginosa twitching motility involves its N-glycosylation and cannot be conferred by the Scavenger Receptor Cysteine-Rich bacteria-binding peptide domain.Scientific reports · 2019Article
- Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots.Genome biology and evolution · 2019Article
- Glycan recognition at the saliva - oral microbiome interface.Cellular immunology · 2018Review
- The Malaria-Protective Human Glycophorin Structural Variant DUP4 Shows Somatic Mosaicism and Association with Hemoglobin Levels.American journal of human genetics · 2018Article
- The scavenging capacity of DMBT1 is impaired by germline deletions.Immunogenetics · 2017Article
- Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa.PLoS pathogens · 2017Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
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.
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