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
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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.
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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Further reading
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Mammals without body hair evolved this trait independently, but relied on the same set of genes to guide the process
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- Evolutionary Biology
Cichlid fishes inhabiting the East African Great Lakes, Victoria, Malawi, and Tanganyika, are textbook examples of parallel evolution, as they have acquired similar traits independently in each of the three lakes during the process of adaptive radiation. In particular, ‘hypertrophied lip’ has been highlighted as a prominent example of parallel evolution. However, the underlying molecular mechanisms remain poorly understood. In this study, we conducted an integrated comparative analysis between the hypertrophied and normal lips of cichlids across three lakes based on histology, proteomics, and transcriptomics. Histological and proteomic analyses revealed that the hypertrophied lips were characterized by enlargement of the proteoglycan-rich layer, in which versican and periostin proteins were abundant. Transcriptome analysis revealed that the expression of extracellular matrix-related genes, including collagens, glycoproteins, and proteoglycans, was higher in hypertrophied lips, regardless of their phylogenetic relationships. In addition, the genes in Wnt signaling pathway, which is involved in promoting proteoglycan expression, was highly expressed in both the juvenile and adult stages of hypertrophied lips. Our comprehensive analyses showed that hypertrophied lips of the three different phylogenetic origins can be explained by similar proteomic and transcriptomic profiles, which may provide important clues into the molecular mechanisms underlying phenotypic parallelisms in East African cichlids.