The genetic structure of domestic rabbits

Abstract

Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ~0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (F(ST) = 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r(2) higher than 0.2, and some LD extended up to 3,200 kb. Much less LD was found among breeds. This advantageous LD structure holds great promise for reducing the interval of association in future mapping studies.

FIG. 1.

Phenotypic variation in domestic and wild rabbits. The bottom left picture shows the typical phenotype of a wild rabbit from the subspecies O. c. cuniculus (kindly provided by P.C. Alves). All the other pictures illustrate the phenotypic diversity observed for numerous traits in domestic rabbits (kindly provided by François Lebas, http://www.cuniculture.info, and references therein).

FIG. 2.

Schematic representation of the coalescent models used to represent the main events of the demographic history of French wild rabbits (left) and domestic rabbits (right). See Materials and Methods for a detailed description of all parameters and assumptions.

FIG. 3.

Box plots depicting genetic differentiation between domestic rabbits and each of the wild rabbit populations considered in this study. Levels of genetic differentiation between domestic rabbits and wild rabbits were estimated using the fixation index (F_ST, A), the net nucleotide divergence (D_a, B), and the average pairwise differences between populations (D_xy, C). Levels of genetic differentiation suggest a closer proximity between domestic rabbits (DOM) and French wild rabbits (OCCFR).

FIG. 4.

Median-joining haplotype networks representing the evolutionary relationships among alleles found in both domestic and wild rabbits. Individuals with missing data were excluded. Size of the circles is proportional to the frequency of each haplotype. Population groups are denoted by black for OCA, white for OCCIP, blue for OCCFR, and red for DOM. Note the substantial haplotype sharing between DOM and OCCFR and the absence of OCA haplotypes in DOM for all genes showing fixed variation between subspecies.

FIG. 5.

Diagram representing the multilocus ML estimate for the strength of the population bottleneck (k). Multilocus ML (y axis, logarithmic scale) of the parameter k (x axis) was estimated as the product of the likelihood for each locus. The best-fitting parameter value of k for each locus was estimated as the proportion of 10,000 simulations whose summary statistics (S, nhaps, and π) were within 20% of the observed values. GPC4 and LUM were not included.

FIG. 6.

Estimates of effective population size (N_e) over time from the present (generations). The relationship between effective population size (y axis) and generation time from the present (x axis) was estimated from LD data using the model of Sved (1971). Champagne Silver (CS), English Spot (ES), French Angora (FA), French Lop (FL), New Zealand White (NZ), and Rex (RX).

FIG. 7.

Plots of LD decay within and among domestic breeds for seven genomic regions. LD was measured using the genotypic r² (y axis) and plotted against physical distance in kilobase pairs (x axis). The solid lines represent a logarithmic trend line fitting the mean of the means r² values for each region and for each distance bin. The corresponding standard deviation is indicated by vertical bars. The dashed lines in each panel represent the mean r² values between unlinked markers. The first six panels show LD within breeds: Champagne Silver (CS), English Spot (ES), French Angora (FA), French Lop (FL), New Zealand White (NZ), and Rex (RX). The bottom panel shows LD considering all six breeds together.