Complementary evolution of coding and noncoding sequence underlies mammalian hairlessness

  1. Amanda Kowalczyk
  2. Maria Chikina
  3. Nathan L Clark  Is a corresponding author
  1. University of Pittsburgh, United States
  2. University of Utah, United States

Abstract

Body hair is a defining mammalian characteristic, but several mammals, such as whales, naked mole-rats, and humans, have notably less hair than others. To find the genetic basis of reduced hair quantity, we used our evolutionary-rates-based method, RERconverge, to identify coding and noncoding sequences that evolve at significantly different rates in so-called hairless mammals compared to hairy mammals. Using RERconverge, we performed a genome-wide scan over 62 mammal species using 19,149 genes and 343,598 conserved noncoding regions to find genetic elements that evolve at significantly different rates in hairless mammals compared to hairy mammals. We show that these rate shifts resulted from relaxation of evolutionary constraint on hair-related sequences in hairless species. In addition to detecting known and potential novel hair-related genes, we also discovered hundreds of putative hair-related regulatory elements. Computational investigation revealed that genes and their associated noncoding regions show different evolutionary patterns and influence different aspects of hair growth and development. Many genes under accelerated evolution are associated with the structure of the hair shaft itself, while evolutionary rate shifts in noncoding regions also included the dermal papilla and matrix regions of the hair follicle that contribute to hair growth and cycling. Genes that were top-ranked for coding sequence acceleration included known hair and skin genes KRT2, KRT35, PKP1, and PTPRM that surprisingly showed no signals of evolutionary rate shifts in nearby noncoding regions. Conversely, accelerated noncoding regions are most strongly enriched near regulatory hair-related genes and microRNAs, such as mir205, ELF3, and FOXC1, that themselves do not show rate shifts in their protein-coding sequences. Such dichotomy highlights the interplay between the evolution of protein sequence and regulatory sequence to contribute to the emergence of a convergent phenotype.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all Figures. Code files are deposited in GitHub at https://github.com/nclark-lab/hairlessness

The following previously published data sets were used

Article and author information

Author details

  1. Amanda Kowalczyk

    Department of Computational Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9061-1336
  2. Maria Chikina

    Department of Computational Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nathan L Clark

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    For correspondence
    nclark@utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0006-8374

Funding

National Institutes of Health (HG009299)

  • Amanda Kowalczyk
  • Maria Chikina
  • Nathan L Clark

National Institutes of Health (EY030546)

  • Amanda Kowalczyk
  • Maria Chikina
  • Nathan L Clark

The funding agencies did not have a role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

Version history

  1. Preprint posted: March 11, 2021 (view preprint)
  2. Received: January 8, 2022
  3. Accepted: November 6, 2022
  4. Accepted Manuscript published: November 7, 2022 (version 1)
  5. Version of Record published: December 30, 2022 (version 2)

Copyright

© 2022, Kowalczyk et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Amanda Kowalczyk
  2. Maria Chikina
  3. Nathan L Clark
(2022)
Complementary evolution of coding and noncoding sequence underlies mammalian hairlessness
eLife 11:e76911.
https://doi.org/10.7554/eLife.76911

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https://doi.org/10.7554/eLife.76911

Further reading

  1. Mammals without body hair evolved this trait independently, but relied on the same set of genes to guide the process

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