Everything is heritable: the power of selection - complex behaviors influenced by many small changes. "Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication " Carneiro et al 2014; excerpts:
"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.
Rabbit domestication was initiated in monasteries in southern France as recently as ~1400 years ago (2). At this time, wild rabbits were mostly restricted to the Iberian Peninsula, where two subspecies occurred (Oryctolagus cuniculus cuniculus and O. c. algirus), and to France, colonized by O. c. cuniculus (Fig. 1B). Additionally, the area of origin of domestic rabbits is still populated with wild rabbits related to the ancestors of the domestic rabbit (3). This recent and well-defined origin provides a major advantage for inferring genetic changes underlying domestication. We performed Sanger sequencing and assembly of a female rabbit genome (4).
To identify genomic regions under selection during domestication, we performed wholegenome resequencing (10× coverage) of pooled samples (table S4) of six different breeds of domestic rabbits (Fig. 1A), 3 pools of wild rabbits from southern France, and 11 pools of wild rabbits from the Iberian Peninsula, representing both subspecies (Fig. 1B). We also sequenced a close relative, the snowshoe hare (Lepus americanus), to deduce the ancestral state at polymorphic sites.
The per-site nucleotide diversity (p) within populations of wild rabbits was in the range of 0.6 to 0.9% (Fig. 1C). Thus, the rabbit is one of the most polymorphic mammals sequenced so far, presumably due to a larger longterm effective population size relative to other sequenced mammals (5). Identity scores confirm that the domestic rabbit is most closely related to wild rabbits from southern France (fig. S1A), and we inferred a strong correlation (r = 0.94) in allele frequencies at most loci between these groups (fig. S1B). The average nucleotide diversity of each sequenced population is consistent with a bottleneck and reduction in genetic diversity when rabbits from the Iberian Peninsula colonized southern France and a second bottleneck during domestication (3) (Fig. 1, B and C). Selective sweeps occur when beneficial genetic variants increase in frequency due to positive selection together with linked neutral sequence variants (6). This results in genomic islands of reduced heterozygosity and increased differentiation between populations around the selected site. We compared genetic diversity between domestic rabbits as one group to wild rabbits representing 14 different locations in France and the Iberian Peninsula. We calculated fixation index (F ST ) values between wild and domestic rabbits and average pooled heterozygosity (H) in domestic rabbits in 50-kb sliding windows across the genome (hereafter referred to as the F ST -H outlier approach). We identified 78 outliers with F ST > 0.35 and H < 0.05 (Fig. 2A, fig. S2, database S1). We also used SweepFinder...This analysis resulted in the identification of 78 significant sweeps (false discovery rate = 5%) (Fig. 2A, database S1). Thirty-one (40%) of these were also detected with the F ST -H approach (Fig. 2A).
Cell fate determination was a strongly enriched GO category (enrichment factor = 4.9) (database S3) for genes near variants with high DAF. We examined the functional importance of 12 SOX2, 4 KLF4, and 1 PAX2 high DAF SNPs associated with this GO category and where all 17 SNPs were distinct to domestic rabbits compared with other sequenced mammals. Electrophoretic mobility shift assay (EMSA) with nuclear extracts from mouse embryonic stem cell-derived neural stem cells revealed specific DNA-protein interactions (Fig. 3, fig. S7, table S7). Four probes, all from the SOX2 region, showed a gel shift difference between wild and domestic alleles. Nuclear extracts from a mouse P19 embryonic carcinoma cell line before and after neuronal differentiation recapitulated these four gel shifts and revealed three additional probes, one in PAX2 and two more in SOX2, that showed gel shift differences between wild-type and mutant probes only after neuronal cells revealed specific DNA-protein interactions (Fig. 3, fig. S7, table S7). Four probes, all from the SOX2 region, showed a gel shift difference between wild and domestic alleles. Nuclear extracts from a mouse P19 embryonic carcinoma cell line before and after neuronal differentiation recapitulated these four gel shifts and revealed three additional probes, one in PAX2 and two more in SOX2, that showed gel shift differences between wild-type and mutant probes only after neuronal great majority of domestic alleles were also found in wild rabbits, implying that directional selection events associated with rabbit domestication are consistent with polygenic and soft sweep modes of selection (18) that primarily acted on standing genetic variation in regulatory regions of the genome. This stands in contrast with breed-specific traits in many domesticated animals that often show a simple genetic basis with complete fixation of causative alleles (19). Our finding that many genes affecting brain and neuronal development have been targeted during rabbit domestication is fully consistent with the view that the most critical phenotypic changes during the initial steps of animal domestication probably involved behavioral traits that allowed animals to tolerate humans and the environment humans offered. On the basis of these observations, we propose that the reason for the paucity of specific fixed domestication genes in animals is that no single genetic change is either necessary or sufficient for domestication. Because of the complex genetic background for tame behavior, we propose that domestic animals evolved by means of many mutations of small effect, rather than by critical changes at only a few domestication loci."
from http://infoproc.blogspot.com/2014/08/rabbit-genome-domestication-via-soft.html
"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.
Rabbit domestication was initiated in monasteries in southern France as recently as ~1400 years ago (2). At this time, wild rabbits were mostly restricted to the Iberian Peninsula, where two subspecies occurred (Oryctolagus cuniculus cuniculus and O. c. algirus), and to France, colonized by O. c. cuniculus (Fig. 1B). Additionally, the area of origin of domestic rabbits is still populated with wild rabbits related to the ancestors of the domestic rabbit (3). This recent and well-defined origin provides a major advantage for inferring genetic changes underlying domestication. We performed Sanger sequencing and assembly of a female rabbit genome (4).
To identify genomic regions under selection during domestication, we performed wholegenome resequencing (10× coverage) of pooled samples (table S4) of six different breeds of domestic rabbits (Fig. 1A), 3 pools of wild rabbits from southern France, and 11 pools of wild rabbits from the Iberian Peninsula, representing both subspecies (Fig. 1B). We also sequenced a close relative, the snowshoe hare (Lepus americanus), to deduce the ancestral state at polymorphic sites.
The per-site nucleotide diversity (p) within populations of wild rabbits was in the range of 0.6 to 0.9% (Fig. 1C). Thus, the rabbit is one of the most polymorphic mammals sequenced so far, presumably due to a larger longterm effective population size relative to other sequenced mammals (5). Identity scores confirm that the domestic rabbit is most closely related to wild rabbits from southern France (fig. S1A), and we inferred a strong correlation (r = 0.94) in allele frequencies at most loci between these groups (fig. S1B). The average nucleotide diversity of each sequenced population is consistent with a bottleneck and reduction in genetic diversity when rabbits from the Iberian Peninsula colonized southern France and a second bottleneck during domestication (3) (Fig. 1, B and C). Selective sweeps occur when beneficial genetic variants increase in frequency due to positive selection together with linked neutral sequence variants (6). This results in genomic islands of reduced heterozygosity and increased differentiation between populations around the selected site. We compared genetic diversity between domestic rabbits as one group to wild rabbits representing 14 different locations in France and the Iberian Peninsula. We calculated fixation index (F ST ) values between wild and domestic rabbits and average pooled heterozygosity (H) in domestic rabbits in 50-kb sliding windows across the genome (hereafter referred to as the F ST -H outlier approach). We identified 78 outliers with F ST > 0.35 and H < 0.05 (Fig. 2A, fig. S2, database S1). We also used SweepFinder...This analysis resulted in the identification of 78 significant sweeps (false discovery rate = 5%) (Fig. 2A, database S1). Thirty-one (40%) of these were also detected with the F ST -H approach (Fig. 2A).
Cell fate determination was a strongly enriched GO category (enrichment factor = 4.9) (database S3) for genes near variants with high DAF. We examined the functional importance of 12 SOX2, 4 KLF4, and 1 PAX2 high DAF SNPs associated with this GO category and where all 17 SNPs were distinct to domestic rabbits compared with other sequenced mammals. Electrophoretic mobility shift assay (EMSA) with nuclear extracts from mouse embryonic stem cell-derived neural stem cells revealed specific DNA-protein interactions (Fig. 3, fig. S7, table S7). Four probes, all from the SOX2 region, showed a gel shift difference between wild and domestic alleles. Nuclear extracts from a mouse P19 embryonic carcinoma cell line before and after neuronal differentiation recapitulated these four gel shifts and revealed three additional probes, one in PAX2 and two more in SOX2, that showed gel shift differences between wild-type and mutant probes only after neuronal cells revealed specific DNA-protein interactions (Fig. 3, fig. S7, table S7). Four probes, all from the SOX2 region, showed a gel shift difference between wild and domestic alleles. Nuclear extracts from a mouse P19 embryonic carcinoma cell line before and after neuronal differentiation recapitulated these four gel shifts and revealed three additional probes, one in PAX2 and two more in SOX2, that showed gel shift differences between wild-type and mutant probes only after neuronal great majority of domestic alleles were also found in wild rabbits, implying that directional selection events associated with rabbit domestication are consistent with polygenic and soft sweep modes of selection (18) that primarily acted on standing genetic variation in regulatory regions of the genome. This stands in contrast with breed-specific traits in many domesticated animals that often show a simple genetic basis with complete fixation of causative alleles (19). Our finding that many genes affecting brain and neuronal development have been targeted during rabbit domestication is fully consistent with the view that the most critical phenotypic changes during the initial steps of animal domestication probably involved behavioral traits that allowed animals to tolerate humans and the environment humans offered. On the basis of these observations, we propose that the reason for the paucity of specific fixed domestication genes in animals is that no single genetic change is either necessary or sufficient for domestication. Because of the complex genetic background for tame behavior, we propose that domestic animals evolved by means of many mutations of small effect, rather than by critical changes at only a few domestication loci."
from http://infoproc.blogspot.com/2014/08/rabbit-genome-domestication-via-soft.html
https://goo.gl/Ybebd1: Profacgen has a mature EMSA experiment platform and extensive experience in nucleotide-protein binding analysis. We perform strict examination on both nucleotide and protein to ensure they are qualified for EMSA before the initiation of each project. We can use radioactive isotope and also other labeling agents such as biotin and FAM to label nucleotides...9w
