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Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans

Author

Listed:
  • PingHsun Hsieh

    (University of Washington School of Medicine)

  • Vy Dang

    (University of Washington School of Medicine
    University of Texas)

  • Mitchell R. Vollger

    (University of Washington School of Medicine)

  • Yafei Mao

    (University of Washington School of Medicine)

  • Tzu-Hsueh Huang

    (University of Washington School of Medicine)

  • Philip C. Dishuck

    (University of Washington School of Medicine)

  • Carl Baker

    (University of Washington School of Medicine)

  • Stuart Cantsilieris

    (University of Washington School of Medicine
    University of Melbourne, Royal Victorian Eye and Ear Hospital)

  • Alexandra P. Lewis

    (University of Washington School of Medicine)

  • Katherine M. Munson

    (University of Washington School of Medicine)

  • Melanie Sorensen

    (University of Washington School of Medicine)

  • AnneMarie E. Welch

    (University of Washington School of Medicine
    The Walter and Eliza Hall Institute of Medical Research)

  • Jason G. Underwood

    (University of Washington School of Medicine
    Pacific Biosciences (PacBio) of California, Incorporated)

  • Evan E. Eichler

    (University of Washington School of Medicine
    University of Washington)

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.

Suggested Citation

  • PingHsun Hsieh & Vy Dang & Mitchell R. Vollger & Yafei Mao & Tzu-Hsueh Huang & Philip C. Dishuck & Carl Baker & Stuart Cantsilieris & Alexandra P. Lewis & Katherine M. Munson & Melanie Sorensen & Anne, 2021. "Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25435-4
    DOI: 10.1038/s41467-021-25435-4
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    Cited by:

    1. Lingzhen Kong & Chen Cheng & Abigael Cheruiyot & Jiayi Yuan & Yichan Yang & Sydney Hwang & Daniel Foust & Ning Tsao & Emily Wilkerson & Nima Mosammaparast & Michael B. Major & David W. Piston & Shan L, 2024. "TCAF1 promotes TRPV2-mediated Ca2+ release in response to cytosolic DNA to protect stressed replication forks," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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