G. Bolet

Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication

Rabbits softly swept to domestication When people domesticate animals, they select for tameness and tolerance of humans. What else do they look for? To identify the selective pressures that led to rabbit domestication, Carneiro et al. sequenced a domestic rabbit genome and compared it to that of its wild brethren (see the Perspective by Lohmueller). Domestication did not involve a single gene changing, but rather many gene alleles changing in frequency between tame and domestic rabbits, known as a soft selective sweep. Many of these alleles have changes that may affect brain development, supporting the idea that tameness involves changes at multiple loci. Science, this issue p. 1074; see also p. 1000 The domestication of rabbits primarily shifted the frequencies of alleles represented, rather than creating new genes. [Also see Perspective by Lohmueller] The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.

The Genetic Structure of Domestic Rabbits

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.

The relationship between rabbit semen characteristics and reproductive performance after artificial insemination

The relationships between several rabbit buck semen traits, concerning either the ejaculate or the dose inseminated (volume, mass motility, pH, percentage of motile sperm (PMS), concentration, number of total and motile sperm per ejaculate and per insemination dose) and the reproductive performance of does was investigated in 839 inseminations involving 54 bucks and 111 does. Four genetic types were involved: INRA1601 strain (A), INRA2066 strain (B) and the two reciprocal crossbreds (AB and BA). The mating design was A x A, B x B, (AB or BA) x (AB or BA). Semen was diluted (1:9) and a constant volume of 0.5 ml was inseminated 2-4h after collection. Therefore, the total number of spermatozoa per dose was variable and proportional to the initial concentration. Mass motility significantly influenced the kindling rate. Taken separately, volume, PMS and concentration did not influence the kindling rate but their product, the number of motile sperm per ejaculate, did. Litter size (total born) was significantly influenced by concentration and all variables depending on it, particularly the number of total and motile sperm per dose. However, reproductive performances were predominantly influenced by the physiological status of the does at insemination (lactation stage and receptivity).

Influence of prolactin on foetal survival in rabbit does

Experiments were conducted to assess the influence of prolactin levels on foetal survival in pregnant does. All the females were mated within 12 h following parturition (Day 0), and slaughtered on Day 28 to study reproductive performance. In Experiment 1, lactation was terminated at birth and females in the treated group (Group P,n = 34) were injected with 1 mg of ovine prolactin daily from Day 7 to Day 21. Females in the control group (Group CP, n=31) received no prolactin. On Day 16, the ovine prolactin concentration in Group P was 32.5 ng ml−1. The concentration of rabbit prolactin was higher and the serum level of progesterone was lower in Group P than in Group CP on Day 16 (P Day 15) was significantly higher in Group P (24.5% vs. 10.6%; P < 0.01). In Experiment 2, females were allowed to suckle seven young and received 1 mg of bromocriptine daily from Day 14 to Day 18 (Group B, n = 34). Females in the control group (Group CB, n=31) received no bromocriptine. The concentration of prolactin was lower in Group B than in Group CB on Days 14 and 18 (P < 0.01), and the concentration of progesterone was higher in Group B on Day 18 (P < 0.01). The ovulation rate and early and late foetal mortality were similar in both groups but the number of resorbed foetuses was higher in Group B than in Group CB (1 vs. 0.5; P < 0.05). These results suggest that hyperprolactinaemia during lactation is responsible for the reduced progesterone concentration and the increased late foetal mortality observed in pregnant lactating does. However, short-term suppression of prolactin release after suckling does not improve foetal survival.

Fertilisation rate and preimplantation embryonic development in two rabbit strains of different fecundity, in purebreeding and crossbreeding

Abstract Does ( n = 289) and males ( n = 82) from two INRA strains selected for litter size, A2066 and A1077, were mated in purebreeding and crossbreeding systems, in a diallel design. Females were killed 28 h (D1), 72 h (D3) or 114 h (D5) post-coitum to assess the fertilisation rate of ova shed and preimplantation embryonic survival. A2066 does shed significantly more ova than A1077 does (+ 1.2). The overall pregnancy rate of ovulating females was 92%, without any effect of dam strain and an unfavourable effect of A2066 sires. Among pregnant females (with at least one live embryo), the mating between A2066 males and females gave a fertilisation rate of ova shed significantly lower (82%) than the three other types of matings, which were not significantly different (93%). In contrast, there were no significant differences between the four types of matings in the survival rate of fertilised eggs at D3 (93%) and D5 (87%), although embryos from A2066 dams at D5 were significantly smaller than those from A1077 dams, whatever the sire. The mucin coat was significantly larger in the eggs of A2066 dams, whatever the sire and the stage of pregnancy. Thus, the superiority of A2066 females in the number of ova shed was completely lost in purebreeding by D1, and was retained only in crossbreeding. This was not due to a heterosis effect on embryo viability, but to some antagonism between A2066 male and female gametes in purebreeding. The reasons for this antagonism have to be studied further.

Levels and Patterns of Genetic Diversity and Population Structure in Domestic Rabbits

Over thousands of years humans changed the genetic and phenotypic composition of several organisms and in the process transformed wild species into domesticated forms. From this close association, domestic animals emerged as important models in biomedical and fundamental research, in addition to their intrinsic economical and cultural value. The domestic rabbit is no exception but few studies have investigated the impact of domestication on its genetic variability. In order to study patterns of genetic structure in domestic rabbits and to quantify the genetic diversity lost with the domestication process, we genotyped 45 microsatellites for 471 individuals belonging to 16 breeds and 13 wild localities. We found that both the initial domestication and the subsequent process of breed formation, when averaged across breeds, culminated in losses of ~20% of genetic diversity present in the ancestral wild population and domestic rabbits as a whole, respectively. Despite the short time elapsed since breed diversification we uncovered a well-defined structure in domestic rabbits where the FST between breeds was 22%. However, we failed to detect deeper levels of structure, probably consequence of a recent and single geographic origin of domestication together with a non-bifurcating process of breed formation, which were often derived from crosses between two or more breeds. Finally, we found evidence for intrabreed stratification that is associated with demographic and selective causes such as formation of strains, colour morphs within the same breed, or country/breeder of origin. These additional layers of population structure within breeds should be taken into account in future mapping studies.

Integrative Biology and Genetic Resources Management

Abstract Integrative Biology is exemplified by a diversity of recently established collaborations to study the genetic diversity of the European rabbit, Oryctolagus cuniculus. Molecular markers were developed and used to investigate the link between wild population decreases or domestication procedures and possible losses of genetic diversity. Simultaneously, a European programme was launched for the management of genetic resources. The Integrative Biology approach shows that changes in genetic diversity are often buffered by the flexibility of rabbit reproductive systems. It appears, also, that all domestic animals belong to a subset of the wild genetic pool of their species without major loss of diversity despite exposure to severe viral infections. Consequently, management of genetic resources for production purposes and conservation or protection of declining Iberian wild populations require different approaches and measures.