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The genetic architecture of gene expression levels in wild baboons.

Tung J, Zhou X, Alberts SC, Stephens M, Gilad Y - Elife (2015)

Bottom Line: Primate evolution has been argued to result, in part, from changes in how genes are regulated.We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set.Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, United States.

ABSTRACT
Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates.

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Correlation between eQTL detection and mean phyloP scores based on100-way vertebrate comparison.Genes with eQTL in both data set or one data set are less conservedacross vertebrates than genes for which no eQTL were detected (n =7,268, p < 10−19).DOI:http://dx.doi.org/10.7554/eLife.04729.021
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fig3s1: Correlation between eQTL detection and mean phyloP scores based on100-way vertebrate comparison.Genes with eQTL in both data set or one data set are less conservedacross vertebrates than genes for which no eQTL were detected (n =7,268, p < 10−19).DOI:http://dx.doi.org/10.7554/eLife.04729.021

Mentions: Interestingly, we found that genes harboring eQTL in baboons were also more likely tohave detectable eQTL in the YRI (hypergeometric test, p = 2.39 ×10−7). Given the sample size limitations of the data sets weconsidered, this overlap suggests that large effect eQTL tend to be nonrandomlyconcentrated in specific gene orthologues. This pattern could arise if the regulationof some genes has been selectively constrained over long periods of evolutionarytime, whereas others have been more permissible to genetic perturbation. Indeed, wefound that the mean per-gene phyloP score calculated based on a 46-way primatecomparison was significantly reduced (reflecting less conservation) for genes withdetectable eQTL in both species, and greatest for genes in which eQTL were notdetected in either case (p < 10−53; Figure 3A). We obtained similar results using phyloP scoresbased on a 100-way vertebrate comparison (p < 10−21; Figure 3—figure supplement 1).10.7554/eLife.04729.020Figure 3.Mixed evidence for negative selection on variants affecting geneexpression level.


The genetic architecture of gene expression levels in wild baboons.

Tung J, Zhou X, Alberts SC, Stephens M, Gilad Y - Elife (2015)

Correlation between eQTL detection and mean phyloP scores based on100-way vertebrate comparison.Genes with eQTL in both data set or one data set are less conservedacross vertebrates than genes for which no eQTL were detected (n =7,268, p < 10−19).DOI:http://dx.doi.org/10.7554/eLife.04729.021
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383332&req=5

fig3s1: Correlation between eQTL detection and mean phyloP scores based on100-way vertebrate comparison.Genes with eQTL in both data set or one data set are less conservedacross vertebrates than genes for which no eQTL were detected (n =7,268, p < 10−19).DOI:http://dx.doi.org/10.7554/eLife.04729.021
Mentions: Interestingly, we found that genes harboring eQTL in baboons were also more likely tohave detectable eQTL in the YRI (hypergeometric test, p = 2.39 ×10−7). Given the sample size limitations of the data sets weconsidered, this overlap suggests that large effect eQTL tend to be nonrandomlyconcentrated in specific gene orthologues. This pattern could arise if the regulationof some genes has been selectively constrained over long periods of evolutionarytime, whereas others have been more permissible to genetic perturbation. Indeed, wefound that the mean per-gene phyloP score calculated based on a 46-way primatecomparison was significantly reduced (reflecting less conservation) for genes withdetectable eQTL in both species, and greatest for genes in which eQTL were notdetected in either case (p < 10−53; Figure 3A). We obtained similar results using phyloP scoresbased on a 100-way vertebrate comparison (p < 10−21; Figure 3—figure supplement 1).10.7554/eLife.04729.020Figure 3.Mixed evidence for negative selection on variants affecting geneexpression level.

Bottom Line: Primate evolution has been argued to result, in part, from changes in how genes are regulated.We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set.Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, United States.

ABSTRACT
Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates.

Show MeSH