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Genomic correlates of relationship QTL involved in fore- versus hind limb divergence in mice.

Pavlicev M, Wagner GP, Noonan JP, Hallgrímsson B, Cheverud JM - Genome Biol Evol (2013)

Bottom Line: Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside.This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms.This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation.

View Article: PubMed Central - PubMed

Affiliation: Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria.

ABSTRACT
Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein-coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals, the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation.

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Proportion of loci with SNPs in limb-specific enhancers. The proportion of loci harboring the limb-specifically marked enhancers in the subset of rQTL (N = 26) and intQTL (N = 48). Although comparable proportions of intQTL and rQTL regions harbor limb-specific enhancers, much greater proportion of these is variable in rQTL.
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evt144-F5: Proportion of loci with SNPs in limb-specific enhancers. The proportion of loci harboring the limb-specifically marked enhancers in the subset of rQTL (N = 26) and intQTL (N = 48). Although comparable proportions of intQTL and rQTL regions harbor limb-specific enhancers, much greater proportion of these is variable in rQTL.

Mentions: Intersecting the limb-specific enhancers with rQTL revealed that a total of 535 limb enhancers (160 at E10.5 and 375 at E11.5) map into 23 rQTL. Of these, 224 (42%) are polymorphic in our population, located within 18 rQTL. This is significant enrichment of SNPs in limb-specific enhancers, relative to the rest of the genome (hypergeometric test, P = 1.3 × 10−10). In contrast, we find no enrichment of polymorphic limb enhancers in intQTL: although 1,100 limb enhancers map into intQTL (297 at E10.5 and 803 at E11.5), of these only 140 (38 at E10.5 and 102 at E11.5) are polymorphic, found in six intQTL. This finding is remarkable because intQTL are enriched in limb enhancers (hypergeometric test, P = 1.6 × 10−5), indicating the presence of limb-expressed genes; however, these enhancers tend not to be polymorphic. In summary, we find that 70% of rQTL harbor polymorphic limb-specific enhancers, whereas this is the case in only 12.5% of intQTL (fig. 5). These results suggest that cis-regulatory limb-specific variation underlies rQTL but not intQTL.Fig. 5.—


Genomic correlates of relationship QTL involved in fore- versus hind limb divergence in mice.

Pavlicev M, Wagner GP, Noonan JP, Hallgrímsson B, Cheverud JM - Genome Biol Evol (2013)

Proportion of loci with SNPs in limb-specific enhancers. The proportion of loci harboring the limb-specifically marked enhancers in the subset of rQTL (N = 26) and intQTL (N = 48). Although comparable proportions of intQTL and rQTL regions harbor limb-specific enhancers, much greater proportion of these is variable in rQTL.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814202&req=5

evt144-F5: Proportion of loci with SNPs in limb-specific enhancers. The proportion of loci harboring the limb-specifically marked enhancers in the subset of rQTL (N = 26) and intQTL (N = 48). Although comparable proportions of intQTL and rQTL regions harbor limb-specific enhancers, much greater proportion of these is variable in rQTL.
Mentions: Intersecting the limb-specific enhancers with rQTL revealed that a total of 535 limb enhancers (160 at E10.5 and 375 at E11.5) map into 23 rQTL. Of these, 224 (42%) are polymorphic in our population, located within 18 rQTL. This is significant enrichment of SNPs in limb-specific enhancers, relative to the rest of the genome (hypergeometric test, P = 1.3 × 10−10). In contrast, we find no enrichment of polymorphic limb enhancers in intQTL: although 1,100 limb enhancers map into intQTL (297 at E10.5 and 803 at E11.5), of these only 140 (38 at E10.5 and 102 at E11.5) are polymorphic, found in six intQTL. This finding is remarkable because intQTL are enriched in limb enhancers (hypergeometric test, P = 1.6 × 10−5), indicating the presence of limb-expressed genes; however, these enhancers tend not to be polymorphic. In summary, we find that 70% of rQTL harbor polymorphic limb-specific enhancers, whereas this is the case in only 12.5% of intQTL (fig. 5). These results suggest that cis-regulatory limb-specific variation underlies rQTL but not intQTL.Fig. 5.—

Bottom Line: Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside.This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms.This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation.

View Article: PubMed Central - PubMed

Affiliation: Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria.

ABSTRACT
Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein-coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals, the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation.

Show MeSH
Related in: MedlinePlus