Balancing selection at the human salivary agglutinin gene (DMBT1) driven by host-microbe interactions

• Published in: iScience 2022-05, Vol.25 (5), p.104189-104189, Article 104189
• Main Authors: Alharbi, Adel F., Sheng, Nongfei, Nicol, Katie, Strömberg, Nicklas, Hollox, Edward J.
• Format: Article
• Language: English
• Subjects: biological sciences; evolutionary mechanisms; genetics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.104189

Discovering loci under balancing selection in humans can identify loci with alleles that affect response to the environment and disease. Genome variation data have identified the 5′ region of the DMBT1 gene as undergoing balancing selection in humans. DMBT1 encodes the pattern-recognition glycoprotein DMBT1, also known as SALSA, gp340, or salivary agglutinin. DMBT1 binds to a variety of pathogens through a tandemly arranged scavenger receptor cysteine-rich (SRCR) domain, with the number of domains polymorphic in humans. We show that the signal of balancing selection is driven by one haplotype usually carrying a shorter SRCR repeat and another usually carrying a longer SRCR repeat. DMBT1 encoded by a shorter SRCR repeat allele does not bind a cariogenic and invasive Streptococcus mutans strain, in contrast to the long SRCR allele that shows binding. Our results suggest that balancing selection at DMBT1 is due to host-microbe interactions of encoded SRCR tandem repeat alleles. [Display omitted] •Clear evidence from many analyses show balancing selection at DMBT1•Scavenger-receptor cysteine-rich domain array associated with balancing selection•Genetic variation, not alternative splicing, responsible for protein isoforms•Long, but not short, DMBT1 isoforms bind a cariogenic strain of Streptococcus mutans Biological sciences; Genetics; Evolutionary mechanisms