Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution

Abstract

Detecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. Here, we combine genome sequencing and functional genomics with genome-wide comparative analyses to investigate the fate of regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of relevant transcription factor binding sites. Importantly, diverged regulatory elements are associated with key genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results provide the first evidence that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.

Bayesian detection of convergent rate changes of conserved noncoding elements on phylogenetic trees

“…The idea of matching sequence divergence profiles of either protein-coding genes or noncoding regions with repeated losses or gains of a given trait in multiple independent lineages to gain insight into the molecular basis of phenotype differences was first proposed as "Forward Genomics" by Hiller et al (2012). Since then, this approach has been used in various groups of organisms, often yielding important insights into genome evolution and links between genotype and phenotype (Chikina et al 2016;Prudent et al 2016;Berger et al 2017;Partha et al 2017;Roscito et al 2017). Compared to previous methods testing a pre-defined evolutionary history, our method can distinguish genomic elements with multiple independent accelerations within a target lineage from a single strong acceleration across the entire lineage.…”