1. Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans
- Author
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Mitchell R. Vollger, Katherine M. Munson, Philip C. Dishuck, Vy Dang, Yafei Mao, PingHsun Hsieh, Tzu-Hsueh Huang, Melanie Sorensen, Alexandra P. Lewis, Carl Baker, AnneMarie E. Welch, Stuart Cantsilieris, Jason G. Underwood, and Evan E. Eichler
- Subjects
DNA Copy Number Variations ,Science ,General Physics and Astronomy ,Locus (genetics) ,Evolutionary biology ,Biology ,Genome informatics ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Haplogroup ,Article ,Evolution, Molecular ,Gene Duplication ,Gene duplication ,Animals ,Humans ,Copy-number variation ,Selection, Genetic ,Phylogeny ,Segmental duplication ,Neanderthals ,Multidisciplinary ,Genome, Human ,Haplotype ,Membrane Proteins ,Hominidae ,General Chemistry ,Haplotypes ,Homo sapiens - Abstract
TRP channel-associated factor 1/2 (TCAF1/TCAF2) proteins antagonistically regulate the cold-sensor protein TRPM8 in multiple human tissues. Understanding their significance has been complicated given the locus spans a gap-ridden region with complex segmental duplications in GRCh38. Using long-read sequencing, we sequence-resolve the locus, annotate full-length TCAF models in primate genomes, and show substantial human-specific TCAF copy number variation. We identify two human super haplogroups, H4 and H5, and establish that TCAF duplications originated ~1.7 million years ago but diversified only in Homo sapiens by recurrent structural mutations. Conversely, in all archaic-hominin samples the fixation for a specific H4 haplotype without duplication is likely due to positive selection. Here, our results of TCAF copy number expansion, selection signals in hominins, and differential TCAF2 expression between haplogroups and high TCAF2 and TRPM8 expression in liver and prostate in modern-day humans imply TCAF diversification among hominins potentially in response to cold or dietary adaptations., Duplications of gene segments can allow novel physiological adaptations to evolve. A detailed analysis of the TCAF gene family in primates and archaic humans suggest rapid duplication and diversification in this gene family is associated with cold or dietary adaptations.
- Published
- 2021