Abstract
Genetic variation in cis-regulatory elements is thought to be a major driving force in morphological and physiological changes. However, identifying transcription factor binding events that code for complex traits remains a challenge, motivating novel means of detecting putatively important binding events. Using a curated set of 1154 high-quality transcription factor motifs, we demonstrate that independently eroded binding sites are enriched for independently lost traits in three distinct pairs of placental mammals. We show that these independently eroded events pinpoint the loss of hindlimbs in dolphin and manatee, degradation of vision in naked mole-rat and star-nosed mole, and the loss of external testes in white rhinoceros and Weddell seal. We additionally show that our method may also be utilized with more than two species. Our study exhibits a novel methodology to detect cis-regulatory mutations which help explain a portion of the molecular mechanism underlying complex trait formation and loss.
Highlights
Genetic variation in cis-regulatory architecture is thought to be a major force in the morphological and physiological divergence of species[1,2,3]
The basic building block of regulatory DNA is thought to be transcription factor binding sites, shortl genomic sequences which attract proteins whose central role is to control the rate of transcription
We asked whether the independent erosion of otherwise highly conserved transcription factor binding sites points to a trait shared between species which have undergone similar adaptations
Summary
Genetic variation in cis-regulatory architecture is thought to be a major force in the morphological and physiological divergence of species[1,2,3] This hypothesis was initially controversial, growing experimental evidence suggests that gene regulation plays a key role in determining phenotypic traits[4,5] such as pelvic reduction in three-spined stickleback[6], loss of wing pigmentation in Drosophila[7], and loss of penile spines in human[8]. These observations motivate studying the biological function of transcription factors, their target genes in different cellular contexts, and the regulatory elements to which they bind[9]. Individual binding sites are less conserved than the average protein coding gene[13,14] or enhancer[14]
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