One of the most abundant proteins in human saliva, mucin-7, is encoded by the MUC7 gene, which harbors copy number variable subexonic repeats (PTS-repeats) that affect the size and glycosylation potential of this protein. We recently documented the adaptive evolution of MUC7 subexonic copy number variation among primates. Yet, the evolution of MUC7 genetic variation in humans remained unexplored. Here, we found that PTS-repeat copy number variation has evolved recurrently in the human lineage, thereby generating multiple haplotypic backgrounds carrying five or six PTS-repeat copy number alleles. Contrary to previous studies, we found no associations between the copy number of PTS-repeats and protection against asthma. Instead, we revealed a significant association of MUC7 haplotypic variation with the composition of the oral microbiome. Furthermore, based on in-depth simulations, we conclude that a divergent MUC7 haplotype likely originated in an unknown African hominin population and introgressed into ancestors of modern Africans.
Bibliographical noteFunding Information:
1Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY 2Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology – Hellas, Heraklion, Crete, Greece 3Institute of Computer Science (ICS), Foundation for Research and Technology – Hellas, Heraklion, Crete, Greece 4Department of Biology and the Institute for CyberScience, Pennsylvania State University, University Park, PA 5Department of Genetics, Cell Biology, and Development, University of Minnesota, Twin Cities, MN 6Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY *Corresponding authors: E-mails: firstname.lastname@example.org; email@example.com. Associate editor: Rasmus Nielsen
The authors thank Derek Taylor, Paul Cullen, and James Berry for critical readings of previous versions of this manuscript. This study is primarily funded by OG’s start-up funds, as well as IMPACT grant both from University at Buffalo Research Foundation. P.P. was funded by the grant FP7 REGPOT-InnovCrete (No. 316223) grant, as well as by the FP7-PEOPLE-2013-IEF EVOGREN (625057). M.D. is supported by funds from the Alfred P. Sloan Foundation. S.R. is funded by NIH grants R01DE019807 and R21DE025826. We thank Andrew Clark, Ruth Ley, and Dirk Gevers for their help with obtaining and analyzing the HMP microbiome and host genetic data, and commenting on the manuscript. The authors declare that there is no conflict of interest with organization regarding to the materials discussed in this article.
- ABC simulation
- human evolution
- recurrent mutation
- structural variation