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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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Differences in the magnitude of ASE vs distance betweensites.(A) Difference in the magnitude of ASE estimated for pairsof tested sites (i.e., absolute difference of the absolute values ofz-scores), by distance between sites. (B) Difference in themagnitude of ASE estimated for pairs of tested sites for genes withsignificant ASE only, where one site in the pair is the site with thebest ASE support for the gene. In both plots, distance categories reflectthe range from the previous category to the labeled max value.DOI:http://dx.doi.org/10.7554/eLife.04729.013
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fig1s10: Differences in the magnitude of ASE vs distance betweensites.(A) Difference in the magnitude of ASE estimated for pairsof tested sites (i.e., absolute difference of the absolute values ofz-scores), by distance between sites. (B) Difference in themagnitude of ASE estimated for pairs of tested sites for genes withsignificant ASE only, where one site in the pair is the site with thebest ASE support for the gene. In both plots, distance categories reflectthe range from the previous category to the labeled max value.DOI:http://dx.doi.org/10.7554/eLife.04729.013

Mentions: Together, our simulations suggest that the MAF spectrum, genetic diversity, and LDpatterns increase the number of genes with detectable eQTL in baboons vs the YRIby 2.35-fold overall (1.34× from the MAF, 1.21× from SNP densityeffects, and 1.43× from LD effects). Further, considering that the effectsize estimates in baboons tended to be larger than in the YRI (mean of 0.96 inbaboons vs mean of 0.80 in YRI), the actual fold increase estimated fromsimulations is approximately 6-fold (Figure4—figure supplement 1: ratio of purple vs orange lines at theseeffect sizes). This estimate is remarkably consistent with empirical results fromour comparison of the real baboon and YRI data, in which we identified 6.16-foldthe number of eQTL in the baboons. One possibility is that this difference arisesfrom a history of known admixture in Amboseli between the dominant yellow baboonpopulation and immigrant anubis baboons (Papio anubis: Alberts and Altmann, 2001; Tung et al., 2008). Thus, it might reflectthe difference between an admixed population and an unadmixed population ratherthan a difference between species. However, this explanation seems unlikelybecause evidence for ASE does not extend further from tested genes in baboonscompared to YRI (Figure 1—figuresupplement 10), and because adding controls for local(chromosome-specific) structure when testing for eQTL still results in a largeexcess of eQTL detected in the baboon data set (∼7× higher than inYRI: ‘Materials and methods’ and Figure 1—figure supplement 11)


The genetic architecture of gene expression levels in wild baboons.

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

Differences in the magnitude of ASE vs distance betweensites.(A) Difference in the magnitude of ASE estimated for pairsof tested sites (i.e., absolute difference of the absolute values ofz-scores), by distance between sites. (B) Difference in themagnitude of ASE estimated for pairs of tested sites for genes withsignificant ASE only, where one site in the pair is the site with thebest ASE support for the gene. In both plots, distance categories reflectthe range from the previous category to the labeled max value.DOI:http://dx.doi.org/10.7554/eLife.04729.013
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383332&req=5

fig1s10: Differences in the magnitude of ASE vs distance betweensites.(A) Difference in the magnitude of ASE estimated for pairsof tested sites (i.e., absolute difference of the absolute values ofz-scores), by distance between sites. (B) Difference in themagnitude of ASE estimated for pairs of tested sites for genes withsignificant ASE only, where one site in the pair is the site with thebest ASE support for the gene. In both plots, distance categories reflectthe range from the previous category to the labeled max value.DOI:http://dx.doi.org/10.7554/eLife.04729.013
Mentions: Together, our simulations suggest that the MAF spectrum, genetic diversity, and LDpatterns increase the number of genes with detectable eQTL in baboons vs the YRIby 2.35-fold overall (1.34× from the MAF, 1.21× from SNP densityeffects, and 1.43× from LD effects). Further, considering that the effectsize estimates in baboons tended to be larger than in the YRI (mean of 0.96 inbaboons vs mean of 0.80 in YRI), the actual fold increase estimated fromsimulations is approximately 6-fold (Figure4—figure supplement 1: ratio of purple vs orange lines at theseeffect sizes). This estimate is remarkably consistent with empirical results fromour comparison of the real baboon and YRI data, in which we identified 6.16-foldthe number of eQTL in the baboons. One possibility is that this difference arisesfrom a history of known admixture in Amboseli between the dominant yellow baboonpopulation and immigrant anubis baboons (Papio anubis: Alberts and Altmann, 2001; Tung et al., 2008). Thus, it might reflectthe difference between an admixed population and an unadmixed population ratherthan a difference between species. However, this explanation seems unlikelybecause evidence for ASE does not extend further from tested genes in baboonscompared to YRI (Figure 1—figuresupplement 10), and because adding controls for local(chromosome-specific) structure when testing for eQTL still results in a largeexcess of eQTL detected in the baboon data set (∼7× higher than inYRI: ‘Materials and methods’ and Figure 1—figure supplement 11)

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