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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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Related in: MedlinePlus

Exonic SNP densities in rQTL and intQTL. Distribution of dN/dS in coding genes in both intervals. Genes from rQTL are shown as red triangles and genes from intQTL intervals as black dots. Although many genes from both intervals overlap, the genes high in nonsynonymous substitution rate are genes from intQTL intervals.
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evt144-F4: Exonic SNP densities in rQTL and intQTL. Distribution of dN/dS in coding genes in both intervals. Genes from rQTL are shown as red triangles and genes from intQTL intervals as black dots. Although many genes from both intervals overlap, the genes high in nonsynonymous substitution rate are genes from intQTL intervals.

Mentions: Figure 4 shows single-gene nonsynonymous versus synonymous substitution rates (dN/dS ratio) within rQTL and intQTL. Although the bulk of genes in rQTL and intQTL have comparable distribution of dN/dS, single genes in intQTL consistently lie above the cloud, indicating that intQTL harbor genes with higher relative density of nonsynonymous SNPs. We also observe a trend to higher density of SNPs in rQTL for most regions, except for the nonsynonymous exonic SNPs. This effect is weak, yet consistent across the regions (fig. 3A; six genic regions analyzed; P = 0.55 = 0.031). Together, these results demonstrate a distinct character of exonic nonsynonymous variation in intQTL and intronic variation in rQTL. Note that the mutations in coding regions are thought to be associated with higher pleiotropy on average than the mutations in noncoding regions (Prud'homme et al. 2007). The detected pattern of exonic SNPs in intQTL and intronic SNPs in rQTL thus is consistent with the prediction of the SPC model (Pavlicev and Wagner 2012) that intQTL cause more pleiotropic and rQTL more character-specific variation.


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)

Exonic SNP densities in rQTL and intQTL. Distribution of dN/dS in coding genes in both intervals. Genes from rQTL are shown as red triangles and genes from intQTL intervals as black dots. Although many genes from both intervals overlap, the genes high in nonsynonymous substitution rate are genes from intQTL intervals.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

evt144-F4: Exonic SNP densities in rQTL and intQTL. Distribution of dN/dS in coding genes in both intervals. Genes from rQTL are shown as red triangles and genes from intQTL intervals as black dots. Although many genes from both intervals overlap, the genes high in nonsynonymous substitution rate are genes from intQTL intervals.
Mentions: Figure 4 shows single-gene nonsynonymous versus synonymous substitution rates (dN/dS ratio) within rQTL and intQTL. Although the bulk of genes in rQTL and intQTL have comparable distribution of dN/dS, single genes in intQTL consistently lie above the cloud, indicating that intQTL harbor genes with higher relative density of nonsynonymous SNPs. We also observe a trend to higher density of SNPs in rQTL for most regions, except for the nonsynonymous exonic SNPs. This effect is weak, yet consistent across the regions (fig. 3A; six genic regions analyzed; P = 0.55 = 0.031). Together, these results demonstrate a distinct character of exonic nonsynonymous variation in intQTL and intronic variation in rQTL. Note that the mutations in coding regions are thought to be associated with higher pleiotropy on average than the mutations in noncoding regions (Prud'homme et al. 2007). The detected pattern of exonic SNPs in intQTL and intronic SNPs in rQTL thus is consistent with the prediction of the SPC model (Pavlicev and Wagner 2012) that intQTL cause more pleiotropic and rQTL more character-specific variation.

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