Identifying the genes underlying quantitative traits: a rationale for the QTN programme

Lee, Young Wha; Gould, Brian W.; Stinchcombe, John R.

doi:10.1093/aobpla/plu004

Cited by 57 publications

(56 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although studies of allele frequency spectra show that purifying selection on functional DNA sequences is prevalent (3)(4)(5), little is known about how the genetic variants under selection relate to phenotype, and ultimately, how phenotypic variation is maintained within populations. Association mapping can identify specific loci influencing phenotypes, providing candidates for further analysis of selection (6). In particular, mapping the local regulatory variants that affect gene expression can identify a large number of genetic loci that affect a phenotype.…”

mentioning

confidence: 99%

Association mapping reveals the role of purifying selection in the maintenance of genomic variation in gene expression

Josephs

Lee

Stinchcombe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

109

128

View full text Add to dashboard Cite

The evolutionary forces that maintain genetic variation in quantitative traits within populations remain poorly understood. One hypothesis suggests that variation is under purifying selection, resulting in an excess of low-frequency variants and a negative correlation between minor allele frequency and selection coefficients. Here, we test these predictions using the genetic loci associated with total expression variation (eQTLs) and allele-specific expression variation (aseQTLs) mapped within a single population of the plant Capsella grandiflora. In addition to finding eQTLs and aseQTLs for a large fraction of genes, we show that alleles at these loci are rarer than expected and exhibit a negative correlation between phenotypic effect size and frequency. Overall, our results show that the distribution of frequencies and effect sizes of the loci responsible for local expression variation within a single outcrossing population are consistent with the effects of purifying selection.gene expression | population genomics | association mapping G enetic variation for quantitative traits persists within populations despite the expectation that prevalent stabilizing selection will reduce genetic variance (1). One hypothesis suggests that variation is under purifying selection, resulting in an excess of low-frequency variants and a negative correlation between minor allele frequency and selection coefficients (2). Although studies of allele frequency spectra show that purifying selection on functional DNA sequences is prevalent (3-5), little is known about how the genetic variants under selection relate to phenotype, and ultimately, how phenotypic variation is maintained within populations. Association mapping can identify specific loci influencing phenotypes, providing candidates for further analysis of selection (6). In particular, mapping the local regulatory variants that affect gene expression can identify a large number of genetic loci that affect a phenotype. Additionally, mapping the genetic basis of gene expression may answer questions about the basic biology of gene regulation, for example, by testing predictions that conserved noncoding sequences ("CNSs") are constrained because they have regulatory function (7).Early eQTL studies mapped expression divergence between two lines, finding that many genes have local expression QTL (8, 9). These studies have provided insight into selection on eQTLs; for example, a correlation between recombination rate and eQTL density implied that background selection is a dominant force acting on expression variation in Caenorhabditis elegans (10), and a skew toward rare allele frequencies in promoters of genes with eQTLs suggests that purifying selection may act on expression variation (11). However, eQTL studies of populationlevel genetic variation have thus far been limited to a few study systems (12-16) and only one study, in humans, has identified a negative correlation between phenotypic effect size and frequency (15). In addition, human eQTL studies have shown that loci ex...

show abstract

mentioning

confidence: 99%

Association mapping reveals the role of purifying selection in the maintenance of genomic variation in gene expression

Josephs

Lee

Stinchcombe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

109

128

View full text Add to dashboard Cite

show abstract

“…All else being equal, traits governed by mutations of large phenotypic effect with low pleiotropy can respond to selection more readily than traits that are complex, highly pleiotropic, and/or strongly correlated with other traits. Hence, the genetic basis of trait differences and covariation influences which phenotypic axes are most likely to respond to selection in new environmental conditions; understanding this underlying architecture therefore provides insight into the genetic mechanisms constraining or facilitating phenotypic evolution (Lee et al 2014). It can also indicate which evolutionary forces are responsible for trait differences within and between species.…”

mentioning

confidence: 99%

Quantitative Genetic Analysis Indicates Natural Selection on Leaf Phenotypes Across Wild Tomato Species (Solanumsect.Lycopersicon; Solanaceae)

2014

View full text Add to dashboard Cite

Adaptive evolution requires both raw genetic material and an accessible path of high fitness from one fitness peak to another. In this study, we used an introgression line (IL) population to map quantitative trait loci (QTL) for leaf traits thought to be associated with adaptation to precipitation in wild tomatoes (Solanum sect. Lycopersicon; Solanaceae). A QTL sign test showed that several traits likely evolved under directional natural selection. Leaf traits correlated across species do not share a common genetic basis, consistent with a scenario in which selection maintains trait covariation unconstrained by pleiotropy or linkage disequilibrium. Two large effect QTL for stomatal distribution colocalized with key genes in the stomatal development pathway, suggesting promising candidates for the molecular bases of adaptation in these species. Furthermore, macroevolutionary transitions between vastly different stomatal distributions may not be constrained when such large-effect mutations are available. Finally, genetic correlations between stomatal traits measured in this study and data on carbon isotope discrimination from the same ILs support a functional hypothesis that the distribution of stomata affects the resistance to CO 2 diffusion inside the leaf, a trait implicated in climatic adaptation in wild tomatoes. Along with evidence from previous comparative and experimental studies, this analysis indicates that leaf traits are an important component of climatic niche adaptation in wild tomatoes and demonstrates that some trait transitions between species could have involved few, large-effect genetic changes, allowing rapid responses to new environmental conditions. T HE course of phenotypic evolution depends upon both the genetic basis of functionally important traits and the mechanistic relationship between traits. All else being equal, traits governed by mutations of large phenotypic effect with low pleiotropy can respond to selection more readily than traits that are complex, highly pleiotropic, and/or strongly correlated with other traits. Hence, the genetic basis of trait differences and covariation influences which phenotypic axes are most likely to respond to selection in new environmental conditions; understanding this underlying architecture therefore provides insight into the genetic mechanisms constraining or facilitating phenotypic evolution (Lee et al. 2014). It can also indicate which evolutionary forces are responsible for trait differences within and between species. When adaptation to a complex ecological niche involves many traits, for example, genetic analysis can determine whether correlations between traits are caused by a shared genetic basis (pleiotropy) or whether natural selection favors trait combinations because they function well together (coselection). The magnitude and direction of allelic effects between phenotypically divergent genotypes can also be used to infer whether this divergence is consistent with directional natural selection (Orr 1998b;Rieseberg et al. 2002)...

show abstract

“…Perhaps more importantly, the pure quantitative genetics approach was overtaken from the 1980s on by the molecular biology revolution, which raised the possibility of identifying individual genes and polymorphisms involved in adaptation, at least if they had large effects. Although it is hotly debated how finding such-probably atypical-genes would advance our general understanding of adaptation (91,126), for better or worse, studies discussing real genes proved rather more influential than those merely containing tables of ANOVA (analysis of variance) results. Today, however, the quantitative genetics approach is experiencing something of a revival, owing to the limited success of large-scale genome-wide association studies (GWASs) in humans.…”

Section: Why Genomics?mentioning

confidence: 99%

Population Genomics for Understanding Adaptation in Wild Plant Species

Weigel

Nordborg

2015

Annu. Rev. Genet.

View full text Add to dashboard Cite

Darwin's theory of evolution by natural selection is the foundation of modern biology. However, it has proven remarkably difficult to demonstrate at the genetic, genomic, and population level exactly how wild species adapt to their natural environments. We discuss how one can use large sets of multiple genome sequences from wild populations to understand adaptation, with an emphasis on the small herbaceous plant Arabidopsis thaliana. We present motivation for such studies; summarize progress in describing whole-genome, species-wide sequence variation; and then discuss what insights have emerged from these resources, either based on sequence information alone or in combination with phenotypic data. We conclude with thoughts on opportunities with other plant species and the impact of expected progress in sequencing technology and genome engineering for studying adaptation in nature.

show abstract

Identifying the genes underlying quantitative traits: a rationale for the QTN programme

Cited by 57 publications

References 132 publications

Association mapping reveals the role of purifying selection in the maintenance of genomic variation in gene expression

Association mapping reveals the role of purifying selection in the maintenance of genomic variation in gene expression

Quantitative Genetic Analysis Indicates Natural Selection on Leaf Phenotypes Across Wild Tomato Species (Solanumsect.Lycopersicon; Solanaceae)

Population Genomics for Understanding Adaptation in Wild Plant Species

Contact Info

Product

Resources

About