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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 analyzed SNPs relative to genes.The locations of all SNPs tested in the eQTL analysis are shown in goldrelative to the 5′ most gene transcription start site (TSS) andthe 3′ most gene transcription end site (TES) for all 10,409genes. The location of all SNPs tested in association with eQTL genes isoverplotted in blue. Gray shaded rectangle denotes the region bounded bythe TSS and TES, with gene lengths divided into 20 bins forvisibility.DOI:http://dx.doi.org/10.7554/eLife.04729.007
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fig1s4: Location of analyzed SNPs relative to genes.The locations of all SNPs tested in the eQTL analysis are shown in goldrelative to the 5′ most gene transcription start site (TSS) andthe 3′ most gene transcription end site (TES) for all 10,409genes. The location of all SNPs tested in association with eQTL genes isoverplotted in blue. Gray shaded rectangle denotes the region bounded bythe TSS and TES, with gene lengths divided into 20 bins forvisibility.DOI:http://dx.doi.org/10.7554/eLife.04729.007

Mentions: We also used the RNA-seq reads to identify segregating genetic variants in theAmboseli population. We considered only high confidence sites that were variablewithin the Amboseli population (‘Materials and methods’; Figure 1—figure supplement 3). Asexpected (Piskol et al., 2013), these siteswere highly enriched in annotated gene bodies (Figure1; Figure 1—figure supplement4). Based on parallel analyses applied to human RNA-seq data, we estimatedapproximately 97% of these sites to be true positives, and a median correlationbetween true genotypes and inferred genotypes of 98.7% (‘Materials andmethods’; Figure 1—figuresupplements 5–6). To identify putative expression quantitative traitloci (eQTL), we focused on variants that passed quality control filters, within 200kb of the gene of interest. Such variants represent likelycis-acting eQTL, which are more readily identifiable in small samplesizes than trans-eQTL. To identify cases of allele-specificexpression, which provides independent but complementary evidence for functionalcis-regulatory variation, we focused on genes for which multipleheterozygotes were identified for variants in the exonic regions of expressed genes.We also required a minimum total read depth at exonic heterozygous sites of 300 reads(which should provide high power to detect modest ASE: Fontanillas et al., 2010), resulting in a total set of 2280genes tested for ASE.10.7554/eLife.04729.003Figure 1.Baboon eQTLs are enriched in and near genes.


The genetic architecture of gene expression levels in wild baboons.

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

Location of analyzed SNPs relative to genes.The locations of all SNPs tested in the eQTL analysis are shown in goldrelative to the 5′ most gene transcription start site (TSS) andthe 3′ most gene transcription end site (TES) for all 10,409genes. The location of all SNPs tested in association with eQTL genes isoverplotted in blue. Gray shaded rectangle denotes the region bounded bythe TSS and TES, with gene lengths divided into 20 bins forvisibility.DOI:http://dx.doi.org/10.7554/eLife.04729.007
© Copyright Policy
Related In: Results  -  Collection

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

fig1s4: Location of analyzed SNPs relative to genes.The locations of all SNPs tested in the eQTL analysis are shown in goldrelative to the 5′ most gene transcription start site (TSS) andthe 3′ most gene transcription end site (TES) for all 10,409genes. The location of all SNPs tested in association with eQTL genes isoverplotted in blue. Gray shaded rectangle denotes the region bounded bythe TSS and TES, with gene lengths divided into 20 bins forvisibility.DOI:http://dx.doi.org/10.7554/eLife.04729.007
Mentions: We also used the RNA-seq reads to identify segregating genetic variants in theAmboseli population. We considered only high confidence sites that were variablewithin the Amboseli population (‘Materials and methods’; Figure 1—figure supplement 3). Asexpected (Piskol et al., 2013), these siteswere highly enriched in annotated gene bodies (Figure1; Figure 1—figure supplement4). Based on parallel analyses applied to human RNA-seq data, we estimatedapproximately 97% of these sites to be true positives, and a median correlationbetween true genotypes and inferred genotypes of 98.7% (‘Materials andmethods’; Figure 1—figuresupplements 5–6). To identify putative expression quantitative traitloci (eQTL), we focused on variants that passed quality control filters, within 200kb of the gene of interest. Such variants represent likelycis-acting eQTL, which are more readily identifiable in small samplesizes than trans-eQTL. To identify cases of allele-specificexpression, which provides independent but complementary evidence for functionalcis-regulatory variation, we focused on genes for which multipleheterozygotes were identified for variants in the exonic regions of expressed genes.We also required a minimum total read depth at exonic heterozygous sites of 300 reads(which should provide high power to detect modest ASE: Fontanillas et al., 2010), resulting in a total set of 2280genes tested for ASE.10.7554/eLife.04729.003Figure 1.Baboon eQTLs are enriched in and near genes.

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