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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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Location of eQTL SNPs relative to genes with and without controllingfor local structure.The locations of all eQTL SNPs (n = 1787) identified in the maineQTL analysis are shown in gold relative to the 5′ most genetranscription start site (TSS) and the 3′ most gene transcriptionend site (TES). eQTL SNPs detected in a parallel analysis controlling forlocal structure (n = 1583) are overplotted in blue. Gray shadedrectangle denotes the region bounded by the TSS and TES, with genelengths divided into 20 bins for visibility. Note that SNPs that falloutside of one focal gene may fall within the boundaries of other genes.Inset: Quantile–quantile plot of eQTL locations in models that doand do not control for local structure (Kolmogorov-Smirnov test, p= 0.577).DOI:http://dx.doi.org/10.7554/eLife.04729.014
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fig1s11: Location of eQTL SNPs relative to genes with and without controllingfor local structure.The locations of all eQTL SNPs (n = 1787) identified in the maineQTL analysis are shown in gold relative to the 5′ most genetranscription start site (TSS) and the 3′ most gene transcriptionend site (TES). eQTL SNPs detected in a parallel analysis controlling forlocal structure (n = 1583) are overplotted in blue. Gray shadedrectangle denotes the region bounded by the TSS and TES, with genelengths divided into 20 bins for visibility. Note that SNPs that falloutside of one focal gene may fall within the boundaries of other genes.Inset: Quantile–quantile plot of eQTL locations in models that doand do not control for local structure (Kolmogorov-Smirnov test, p= 0.577).DOI:http://dx.doi.org/10.7554/eLife.04729.014

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)

Location of eQTL SNPs relative to genes with and without controllingfor local structure.The locations of all eQTL SNPs (n = 1787) identified in the maineQTL analysis are shown in gold relative to the 5′ most genetranscription start site (TSS) and the 3′ most gene transcriptionend site (TES). eQTL SNPs detected in a parallel analysis controlling forlocal structure (n = 1583) are overplotted in blue. Gray shadedrectangle denotes the region bounded by the TSS and TES, with genelengths divided into 20 bins for visibility. Note that SNPs that falloutside of one focal gene may fall within the boundaries of other genes.Inset: Quantile–quantile plot of eQTL locations in models that doand do not control for local structure (Kolmogorov-Smirnov test, p= 0.577).DOI:http://dx.doi.org/10.7554/eLife.04729.014
© Copyright Policy
Related In: Results  -  Collection

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

fig1s11: Location of eQTL SNPs relative to genes with and without controllingfor local structure.The locations of all eQTL SNPs (n = 1787) identified in the maineQTL analysis are shown in gold relative to the 5′ most genetranscription start site (TSS) and the 3′ most gene transcriptionend site (TES). eQTL SNPs detected in a parallel analysis controlling forlocal structure (n = 1583) are overplotted in blue. Gray shadedrectangle denotes the region bounded by the TSS and TES, with genelengths divided into 20 bins for visibility. Note that SNPs that falloutside of one focal gene may fall within the boundaries of other genes.Inset: Quantile–quantile plot of eQTL locations in models that doand do not control for local structure (Kolmogorov-Smirnov test, p= 0.577).DOI:http://dx.doi.org/10.7554/eLife.04729.014
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