Parallel Evolution at the Regulatory Base-Pair Level Contributes to Mammalian Interspecific Differences in Polygenic Traits

Abstract

Abstract Parallel evolution occurs when distinct lineages with similar ancestral states converge on a new phenotype. Parallel evolution has been well documented at the organ, gene pathway, and amino acid sequence level but in theory, it can also occur at individual nucleotides within noncoding regions. To examine the role of parallel evolution in shaping the biology of mammalian complex traits, we used data on single-nucleotide polymorphisms (SNPs) influencing human intraspecific variation to predict trait values in other species for 11 complex traits. We found that the alleles at SNP positions associated with human intraspecific height and red blood cell (RBC) count variation are associated with interspecific variation in the corresponding traits across mammals. These associations hold for deeper branches of mammalian evolution as well as between strains of collaborative cross mice. While variation in RBC count between primates uses both ancient and more recently evolved genomic regions, we found that only primate-specific elements were correlated with primate body size. We show that the SNP positions driving these signals are flanked by conserved sequences, maintain synteny with target genes, and overlap transcription factor binding sites. This work highlights the potential of conserved but tunable regulatory elements to be reused in parallel to facilitate evolutionary adaptation in mammals.