Fur Real: Exploring Mammalian Hairiness and Evolutionary Mysteries

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Researchers find hundreds of genes and non-coding elements that underlie the basis of the evolution of mammalian hairlessness. This research can be used for hair growth therapies in the future and give us further insight into the molecular basis for hair growth.

          Have you ever noticed that certain animals seem to have heaps of hair, while others remain almost entirely hairless? Some animals that seem to have barely any hair include rhinos, elephants, whales, dolphins, porpoises, and even us, humans. Large terrestrial animals typically lack hair to allocate their body heat better (Fuller et al. 2016) and marine animals likely adapted hairlessness in response to their marine environment (Chen et al. 2013). While the evolution of hairlessness in humans is not quite known, understanding the genetic mechanisms behind how the hairless phenotype arose can illuminate evolutionary relationships among mammals and give us a better understanding of how a similar phenotype arose throughout several different mammal species (Kowalczyk et al. 2022). Researchers Kowalczyk, Chikina, and Clark set out to answer this question using a series of computational approaches that illuminate the rate at which mutations in genes and non-coding elements related to hairlessness arose.

          During their investigation, the researchers found that the hairless phenotype arose separately in nine lineages in mammals, which hints that convergent evolution is responsible for mammalian hairlessness. Convergent evolution means that instead of the common ancestor of all mammals being hairless, hairlessness arose at separate times for marine animals, humans, elephants, and other hairless mammal species. Then, to find out which genes were evolving the fastest in hairless mammalian lineages, researchers used RERconverge, a computational program. They found that genes relating to hair follicles and skin were the most significant in their analysis.

          Once the researchers found that skin and hair-related genes were selected for the most in hairless mammals, they then attempted to find out which areas of the hair follicle these genes and related non-coding elements (parts of the genome that are responsible for regulating gene expression) were under the most selective pressure. They found that the coding regions, or regions of the DNA that directly code for a protein, were under accelerated evolution (more mutations happening than expected by chance) in the hair cuticle, cortex, and medulla which comprise the hair shaft (see figure 1). On the other hand, non-coding regions were under accelerated evolution in the dermal papilla, which is responsible for the regulation of hair growth (Veraitch et al. 2017), and decelerated evolution (fewer mutations happening than expected by chance) in the matrix, which carries out the instructions given by the dermal papilla to grow or not grow hair. These findings suggests that the non-coding and regulatory elements in DNA may drive hair growth more than the actual coding regions in the DNA. This could be because coding regions are responsible for more than just hair growth, so excess mutations could lead to a potentially harmful phenotype. Thus, it would make sense for more mutations to accrue in the non-coding regions, that can either activate or inactive hair growth indirectly.

          The results from this thorough analysis show that non-coding elements may contribute more to the evolution of mammalian hairlessness and that the overall phenotype of mammalian hairlessness has arisen multiple times throughout evolutionary history. In the future, it would be helpful to conduct studies that can lead to hair therapies for balding patients that target genes and regulatory elements that are involved in a hairless phenotype. Additionally, with further research into hair phenotypes, certain gene therapies could be used to treat certain conditions such as uncombable hair syndrome, alopecia, and hirsutism (excess hair growth). The RERConverge program could also be used in future studies to examine other traits that have been under selective pressure in certain animal, plant, and bacteria groups. This could elucidate our current understanding of how evolution works on certain traits in different organisms. While the program does not establish causality for any genes or coding regions, it serves as a phenomenal avenue for future genomic exploration.

References

Chen Z., Z. Wang, S. Xu, K. Zhou, and G. Yang, 2013 Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans. BMC Evol Biol 13: 34. https://doi.org/10.1186/1471-2148-13-34

Fuller A., D. Mitchell, S. K. Maloney, and R. S. Hetem, 2016 Towards a mechanistic understanding of the responses of large terrestrial mammals to heat and aridity associated with climate change. Climate Change Responses 3: 10. https://doi.org/10.1186/s40665-016-0024-1

Kowalczyk A., M. Chikina, and N. Clark, 2022 Complementary evolution of coding and noncoding sequence underlies mammalian hairlessness, (A. Rokas, M. Przeworski, and P. H. Sudmant, Eds.). eLife 11: e76911. https://doi.org/10.7554/eLife.76911

Veraitch O., Y. Mabuchi, Y. Matsuzaki, T. Sasaki, H. Okuno, et al., 2017 Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells. Sci Rep 7: 42777. https://doi.org/10.1038/srep42777

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