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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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The topology and evolution of pleiotropy. (A) The phenotypic domain of pleiotropic locus (intQTL; blue) is modified by the local action of rQTL (red). (B) Evolutionary scenario: selection on trait 1 (black arrow) results in a change in pleiotropic locus, which propagates to trait 2 (U-shaped arrow) and is followed in the next step by a local compensation of side effects in non-focal traits.
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evt144-F1: The topology and evolution of pleiotropy. (A) The phenotypic domain of pleiotropic locus (intQTL; blue) is modified by the local action of rQTL (red). (B) Evolutionary scenario: selection on trait 1 (black arrow) results in a change in pleiotropic locus, which propagates to trait 2 (U-shaped arrow) and is followed in the next step by a local compensation of side effects in non-focal traits.

Mentions: It is, however, unknown how such topology of developmental interactions evolves and how it relates to the variational patterns at the population level. Generally, developmental regulation is thought to naturally result in pleiotropy of, and epistasis between, the effects of genetic polymorphisms on the phenotypic traits (Gibson 1996; Gjuvsland et al. 2007). Here, we build on a recent model of evolution of pleiotropy by epistatic interactions (Pavlicev and Wagner 2012). This model suggests that covariance evolves in two steps: a selection response in a focal trait and epistatic compensatory modification of correlated side effects in another trait (fig. 1B); hence the name selection–pleiotropy–compensation or SPC model. Due to epistasis, the contribution of pleiotropic mutation to trait covariance changes from pre- to post-compensatory genetic background. In this model, genetic individuation of characters occurs by coadaptation between the pleiotropic and the local compensatory gene. When alleles at the pleiotropic and the compensatory locus segregate, such topology is detected as genetic variation in pleiotropic effects.Fig. 1.—


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)

The topology and evolution of pleiotropy. (A) The phenotypic domain of pleiotropic locus (intQTL; blue) is modified by the local action of rQTL (red). (B) Evolutionary scenario: selection on trait 1 (black arrow) results in a change in pleiotropic locus, which propagates to trait 2 (U-shaped arrow) and is followed in the next step by a local compensation of side effects in non-focal traits.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

evt144-F1: The topology and evolution of pleiotropy. (A) The phenotypic domain of pleiotropic locus (intQTL; blue) is modified by the local action of rQTL (red). (B) Evolutionary scenario: selection on trait 1 (black arrow) results in a change in pleiotropic locus, which propagates to trait 2 (U-shaped arrow) and is followed in the next step by a local compensation of side effects in non-focal traits.
Mentions: It is, however, unknown how such topology of developmental interactions evolves and how it relates to the variational patterns at the population level. Generally, developmental regulation is thought to naturally result in pleiotropy of, and epistasis between, the effects of genetic polymorphisms on the phenotypic traits (Gibson 1996; Gjuvsland et al. 2007). Here, we build on a recent model of evolution of pleiotropy by epistatic interactions (Pavlicev and Wagner 2012). This model suggests that covariance evolves in two steps: a selection response in a focal trait and epistatic compensatory modification of correlated side effects in another trait (fig. 1B); hence the name selection–pleiotropy–compensation or SPC model. Due to epistasis, the contribution of pleiotropic mutation to trait covariance changes from pre- to post-compensatory genetic background. In this model, genetic individuation of characters occurs by coadaptation between the pleiotropic and the local compensatory gene. When alleles at the pleiotropic and the compensatory locus segregate, such topology is detected as genetic variation in pleiotropic effects.Fig. 1.—

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