Selective breeding and selection mapping using a novel wild-derived heterogeneous stock of mice revealed two closely-linked loci for tameness

Yuki Matsumoto,Richard F Mott,Hirofumi Nakaoka,Jo Nishino,Akira Tanave,Toshiyuki Takano-Shimizu,Tatsuhiko Goto,Tsuyoshi Koide

doi:10.1038/s41598-017-04869-1

Abstract

Tameness is a major behavioral factor for domestication, and can be divided into two potential components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). We identified genetic loci for active tameness through selective breeding, selection mapping, and association analysis. In previous work using laboratory and wild mouse strains, we found that laboratory strains were predominantly selected for passive tameness but not active tameness during their domestication. To identify genetic regions associated with active tameness, we applied selective breeding over 9 generations for contacting, a behavioural parameter strongly associated with active tameness. The prerequisite for successful selective breeding is high genetic variation in the target population, so we established and used a novel resource, wild-derived heterogeneous stock (WHS) mice from eight wild strains. The mice had genetic variations not present in other outbred mouse populations. Selective breeding of the WHS mice increased the contacting level through the generations. Selection mapping was applied to the selected population using a simulation based on a non-selection model and inferred haplotype data derived from single-nucleotide polymorphisms. We found a genomic signature for selection on chromosome 11 containing two closely linked loci.

Highlights

Tameness is one of the major factors selected during domestication[1,2,3]
The genotypes of the eight founder strains were compared with the genotypes of 46 other strains for which data are available from the UNC Systems Genetics at the University of North Carolina
A neighbor-joining (NJ) tree using these SNPs revealed that the wild-derived heterogeneous stock (WHS) founders have different genetic characteristics from other heterogeneous stocks (HSs) that are descended from laboratory strains and from the Diversity Outbred (DO) whose founders include wild-derived strains (Fig. 1a)[11]

Summary

Introduction

Tameness is one of the major factors selected during domestication[1,2,3]. Allele frequency changes have been shown to occur over generations in a population of captive wild animals adapting to humans[4]. The passive tame and stay-on-hand tests are used to evaluate reluctance to avoid a human hand (passive tameness) We used these behavioral tests to assess seven laboratory strains of mice established up to a century ago from domesticated mice of European origin (Mus musculus domesticus) and ten wild strains, more-recently derived from three major genetically diverse subspecies of mice, It is crucial that a mouse stock that exhibits high levels of active tameness is established for use in studies of active tameness because such a strain has not previously been established, and is essential to allow the effects of genes to be examined in future studies From this point of view, the commonly used QTL mapping method using a F2 hybrid population produced using two different inbred strains will not be suitable for analyzing genetic loci related to tameness. We performed selection mapping to identify loci associated with this trait

Objectives

Methods

Results

Conclusion