Bioinformatics analysis of candidate domestication regions in Dog genome

Abstract

The process of domestication exerts intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the sequence and structure of genomic regulatory elements may provide an explanation for the extensive variation in the phenotypic traits observed in domesticated species. Based on the recent evidence, dog has emerged as a premier species for the study of morphology, behavior and disease. The profound availability of high quality dog genome sequence enhanced the possibility of study design using this system for domestication. In current study, we focused on the candidate domestication region of dog genome that contains α-Amino-β-Carboxymuconate-ε-semialdehyde decarboxylase (ACMSD). ACMSD controls the metabolic fate of tryptophan catabolism through kynurenine pathway. This study was aimed to elucidate evolutionary and structural insights of ACMSD to discern its role in domestication by revealing its sequence and structural evolutionary patterns among vertebrates and specifically in the domesticated dog (Canis familiaris) and grey wolf (Canis lupus). Phylogenetic analysis by Maximum Likelihood (ML) method revealed high conservation of ACMSD during vertebrates’ evolution. Analysis of non-synonymous and synonymous substitution ratios (Ka/Ks ratio) suggested that ACMSD gene sequences undergone strong negative selection over the course of evolution in human, dog and wolf. Sequence analysis demonstrated a unique motif in wolf that was missing in dog and human. As structural dynamics exhibited more conservation than sequence, the observed motif may have some role in the regulation of domestication and associated behavioral variation in wolf. Further analysis of ACMSD in other species will uncover the possible role of this motif, and its possible influence on domestication and neurodegeneration. Overall, this study may prove a milestone for potential functional and evolutionary studies to elucidate the genetic underpinnings of ACMSD functional role in domestication.