Complementary evolution of coding and noncoding sequence underlies mammalian hairlessness
Authors: Amanda Kowalczyk 1; Maria Chikina 2; Nathan Clark 3
Affiliations: 1) Carnegie Mellon University, Pittsburgh, PA; 2) University of Pittsburgh, Pittsburgh, PA; 3) University of Utah, Salt Lake City, UT
Keywords: Comparative genomics & genome evolution
Although hair is a defining mammalian characteristic, several mammals, such as elephants, naked mole-rats, and humans, have substantially reduced hair coverage. In these so-called "hairless" mammals, their limited hair differs both in quantity and localization from other mammals, suggesting potential roles of gene regulation and gene sequence changes underlying phenotypic diversity. Thus, the hairless phenotype is a dynamic system in which to study interplays in evolution of coding and regulatory sequence.
Elucidating these genotype-phenotype relationships is a key question in biology. One way to answer this question is a computational method called RERconverge that performs a genome-wide scan to find associations between evolutionary rates of genetic elements and convergently-evolving traits. As similar traits evolve independently in different species, similar selective pressure shifts in genetic sequence can accompany and drive phenotypic changes. RERconverge detects these selective pressure shifts as quantified by shifts in evolutionary rate.
RERconverge was used to identify the genetic basis of reduced hair quantity in mammals using sequence for protein-coding genes and approximately 350,000 noncoding regions. RERconverge successfully identified genes and noncoding regions associated with keratinization, cornification, and hair-related mouse knockout phenotypes. A skin- and hair-associated microRNA, MIR205, was likewise found to have a significant enrichment of quickly evolving noncoding elements in its vicinity. RERconverge also identified genes and non-coding elements associated with changes in skin, many of which may be complementary to hair loss, such as changes in genomic regions related to UV light DNA damage repair. Other genes detected remain poorly functionally characterized, and nearly all noncoding regions remain untested. These regions represent good candidate genes and regulatory elements to test experimentally for association with hair growth.
Despite the similar functional categories identified in both coding and noncoding sequence analyses, precise regions identified were strikingly different. Most genes that showed significant evolutionary rate shifts associated with hairlessness did not show the same in their nearby noncoding regions and vice-versa. Such findings suggest a complementary interplay between evolution of regulatory and protein-coding regions underlying mammalian hairlessness.