Analysis of structural diversity in wolf-like canids reveals post-domestication variants.

Oscar Ramirez,Carles Vilà,Jessica Hernandez-Rodriguez,Belen Lorente-Galdos,Carles Lalueza-Fox,Javier Quilez,Iñigo Olalde,Matthew T Webster,Robert K Wayne,Jonas Berglund,Tomas Marques-Bonet

doi:10.1186/1471-2164-15-465

Abstract

BackgroundAlthough a variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood. Further, very limited knowledge exists on structural variation in the gray wolf, the ancestor of the dog, or other closely related wild canids. Documenting CNVs variation in wild canids is essential to identify ancestral states and variation that may have appeared after domestication.ResultsIn this work, we genotyped 1,611 dog CNVs in 23 wolf-like canids (4 purebred dogs, one dingo, 15 gray wolves, one red wolf, one coyote and one golden jackal) to identify CNVs that may have arisen after domestication. We have found an increase in GC-rich regions close to the breakpoints and around 1 kb away from them suggesting that some common motifs might be associated with the formation of CNVs. Among the CNV regions that showed the largest differentiation between dogs and wild canids we found 12 genes, nine of which are related to two known functions associated with dog domestication; growth (PDE4D, CRTC3 and NEB) and neurological function (PDE4D, EML5, ZNF500, SLC6A11, ELAVL2, RGS7 and CTSB).ConclusionsOur results provide insight into the evolution of structural variation in canines, where recombination is not regulated by PRDM9 due to the inactivation of this gene. We also identified genes within the most differentiated CNV regions between dogs and wolves, which could reflect selection during the domestication process.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-465) contains supplementary material, which is available to authorized users.

Highlights

A variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood
Four large-scale surveys of structural variation in dogs have been carried out using array comparative genomic hybridization [18,19,20,21], providing the first catalog of CNVs in the dog genome and candidate CNVs for breed-specific traits
In a first discovery stage, we identified CNVs using a conservative approach based on the combination on two methods: a Reversible Jump hidden Markov Model [26] and the procedure described in [21]

Summary

Introduction

A variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood. Very limited knowledge exists on structural variation in the gray wolf, the ancestor of the dog, or other closely related wild canids. The use of mtDNA, microsatellites, SNP arrays and whole genome sequencing has revealed some of the genetic changes underlying the generation of phenotypic diversity under domestication. Fewer studies of structural variation have been performed in dogs compared to studies using SNPs or microsatellite loci, some examples of copy number variants (CNVs) that affect phenotype have been identified [2,16,17]. Very limited knowledge exists on the evolution and timing of CNV events

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Results

Conclusion