There are at least 20 mucin genes (MUC) in human and mouse genomes, dispersed onto 11 different chromosomal locations. There are two clusters of four MUC genes, three clusters of two MUC genes, and the remaining six (including MUC7 on Chr 4q13) exist as single genes alone, rather than within any cluster. MUC7 encodes one of the most abundant proteins in human saliva. Mucin-7 is a small soluble protein which, like other mucins, harbors subexonic repeat sequences rich in the amino acids proline, threonine, and serine (PTS repeats). PTS repeats are primary targets for O-glycosylation of the protein and, hence, are primary targets for various commensal and pathogenic microorganisms.
MUC7 bears no genetic homology to any of the other mucin genes, originating in the ancestor of placental mammals, making it one of the youngest members of the mucin functional family of proteins. The number of PTS repeats in the human MUC7 protein varies between five and six haploid copies, but origins and evolution of the haplotypes harboring these different copy-number variants (CNVs) are unknown. Previous studies in three independent cohorts suggested that the less-common 5-copy allele is associated with protection against asthma; however, association of this locus with asthma was not confirmed in genome-wide association studies (GWAS) of larger cohorts. Still, it remains unresolved whether MUC7 genetic variation is indeed associated with protection against asthma.
To better address the question of disease association of MUC7 PTS-repeats, authors [see attached] resolved the haplotype architecture of the locus and investigated genetic variation of MUC7 in humans from a more fundamental, evolutionary perspective. Authors found that PTS-repeat CNVs have evolved recurrently in the human lineage –– thereby generating multiple haplotypic backgrounds carrying five or six PTS-repeat copy-number alleles. Contrary to previous publications, authors found no association between copy number of PTS repeats and protection against asthma. Instead, they discovered a significant association of MUC7 haplotype variation with composition of the oral microbiome. Furthermore, based on intriguing in-depth computer simulations, authors conclude that a divergent MUC7 haplotype likely originated in a currently unknown African hominin population that then introgressed (via breeding) into ancestors of modern Africans..!
Mol Biol Evol 10.1093/molbev/msx206(2017)