TY - JOUR
T1 - Archaic Hominin Introgression in Africa Contributes to Functional Salivary MUC7 Genetic Variation
AU - Xu, Duo
AU - Pavlidis, Pavlos
AU - Taskent, Recep Ozgur
AU - Alachiotis, Nikolaos
AU - Flanagan, Colin
AU - Degiorgio, Michael
AU - Blekhman, Ran
AU - Ruhl, Stefan
AU - Gokcumen, Omer
N1 - Funding 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: [email protected]; [email protected]. Associate editor: Rasmus Nielsen
Funding Information:
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.
Publisher Copyright:
©2017 The Author.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - ABC simulation
KW - CNV
KW - human evolution
KW - microbiome
KW - mucin
KW - recurrent mutation
KW - saliva
KW - structural variation
UR - http://www.scopus.com/inward/record.url?scp=85029873705&partnerID=8YFLogxK
U2 - 10.1093/molbev/msx206
DO - 10.1093/molbev/msx206
M3 - Article
C2 - 28957509
AN - SCOPUS:85029873705
SN - 0737-4038
VL - 34
SP - 2704
EP - 2715
JO - Molecular Biology and Evolution
JF - Molecular Biology and Evolution
IS - 10
ER -
