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Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans
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Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans
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Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans
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Journal Article
Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans
2021
Overview
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.
