Complementary evolution of coding and noncoding sequence underlies mammalian hairlessness
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
-
100-way vertebrate genome alignmentUCSC Genome Browser alignment.
Article and author information
Author details
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
- Antonis Rokas, Vanderbilt University, United States
Version history
- Preprint posted: March 11, 2021 (view preprint)
- Received: January 8, 2022
- Accepted: November 6, 2022
- Accepted Manuscript published: November 7, 2022 (version 1)
- 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.
Metrics
-
- 7,274
- Page views
-
- 885
- Downloads
-
- 11
- Citations
Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
Mammals without body hair evolved this trait independently, but relied on the same set of genes to guide the process
-
- Evolutionary Biology
Understanding how plants adapt to changing environments and the potential contribution of transposable elements (TEs) to this process is a key question in evolutionary genomics. While TEs have recently been put forward as active players in the context of adaptation, few studies have thoroughly investigated their precise role in plant evolution. Here, we used the wild Mediterranean grass Brachypodium distachyon as a model species to identify and quantify the forces acting on TEs during the adaptation of this species to various conditions, across its entire geographic range. Using sequencing data from more than 320 natural B. distachyon accessions and a suite of population genomics approaches, we reveal that putatively adaptive TE polymorphisms are rare in wild B. distachyon populations. After accounting for changes in past TE activity, we show that only a small proportion of TE polymorphisms evolved neutrally (<10%), while the vast majority of them are under moderate purifying selection regardless of their distance to genes. TE polymorphisms should not be ignored when conducting evolutionary studies, as they can be linked to adaptation. However, our study clearly shows that while they have a large potential to cause phenotypic variation in B. distachyon, they are not favored during evolution and adaptation over other types of mutations (such as point mutations) in this species.