The MUC19 Gene: An Evolutionary History of Recurrent Introgression and Natural Selection

We study the gene MUC19, for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype is under positive selection and carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations. Finally, some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression.

All scripts for the entire project can be found here: https://github.com/David-Peede/MUC19/tree/main

Files

• ZENODO_README.md: Description of datasets.
• papuan_phased_hmmmix_haploid_tracts_per_ind.tar.gz: Unfiltered, decoded, and annotated hmmix autosomal tracts for all Papuans.
• tgp_hmmmix_haploid_tracts_per_ind.tar.gz: Unfiltered, decoded, and annotated hmmix autosomal tracts for the 1KG individuals.
• den_tracts_in_pap.tar.gz: Coordinates for the putative Denisovan tracts for the Papuan individuals.
• tgp_hmmix_haplotype_tracts_chr12.csv.gz: Pre-processed Chr12 archaic tracts for the 1KG individuals.
• tgp_hmmix_haplotype_tracts_muc19.csv.gz: Pre-processed archaic tracts overlapping the MUC19 region for the 1KG individuals.
• papuan_hmmix_haplotype_tracts.csv.gz: Pre-processed autosomal archaic tracts for the Papuan individuals.
• dataset_1.csv.gz: Sequence divergence results between the haplotypes in the 1KG and the four high-coverage archaic individuals at the focal 72kb MUC19 region.
• dataset_2.csv.gz: Sequence divergence results between the haplotypes in the 1KG and the four high-coverage archaic individuals at the focal 742kb MUC19 region.
• dataset_3.csv.gz: Sequence divergence results between the haplotypes in the 1KG and the phased late Neanderthal haplotypes at the focal 72kb MUC19 region.