ArticleAmerican journal of human genetics2014
Gene age predicts the strength of purifying selection acting on gene expression variation in humans.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
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- Evolution of Dosage-Sensitive Genes by Tissue-Restricted Expression Changes.Genome biology and evolution · 2025Article
- Deleterious Mutations and the Rare Allele Burden on Rice Gene Expression.Molecular biology and evolution · 2022Article
- Adaptive eQTLs reveal the evolutionary impacts of pleiotropy and tissue-specificity while contributing to health and disease.HGG advances · 2022Article
- Molecular evolution and the decline of purifying selection with age.Nature communications · 2021Article
- Trans-ancestral dissection of urate- and gout-associated major loci SLC2A9 and ABCG2 reveals primate-specific regulatory effects.Journal of human genetics · 2021Article
- A systems genetics approach reveals environment-dependent associations between SNPs, protein coexpression, and drought-related traits in maize.Genome research · 2020Article
- Gene expression variability in human and chimpanzee populations share common determinants.eLife · 2020Article
- NCBoost classifies pathogenic non-coding variants in Mendelian diseases through supervised learning on purifying selection signals in humans.Genome biology · 2019Article
- Intronic CNVs and gene expression variation in human populations.PLoS genetics · 2019Article
- Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals.Journal of the Endocrine Society · 2018Article
- Slightly deleterious genomic variants and transcriptome perturbations in Down syndrome embryonic selection.Genome research · 2018Article
- How the evolution of multicellularity set the stage for cancer.British journal of cancer · 2018Review
- An analysis of aging-related genes derived from the Genotype-Tissue Expression project (GTEx).Cell death discovery · 2018Article
- Gene co-expression network connectivity is an important determinant of selective constraint.PLoS genetics · 2017Article
- What Signatures Dominantly Associate with Gene Age?Genome biology and evolution · 2016Article
- Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals.Science (New York, N.Y.) · 2016Article
- Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation.American journal of human genetics · 2016Article
- Host gene constraints and genomic context impact the expression and evolution of human microRNAs.Nature communications · 2016Article
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Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
Abstract
Gene expression levels can be subject to selection. We hypothesized that the age of gene origin is associated with expression constraints, given that it affects the level of gene integration into the functional cellular environment. By studying the genetic variation affecting gene expression levels (cis expression quantitative trait loci [cis-eQTLs]) and protein levels (cis protein QTLs [cis-pQTLs]), we determined that young, primate-specific genes are enriched in cis-eQTLs and cis-pQTLs. Compared to cis-eQTLs of old genes originating before the zebrafish divergence, cis-eQTLs of young genes have a higher effect size, are located closer to the transcription start site, are more significant, and tend to influence genes in multiple tissues and populations. These results suggest that the expression constraint of each gene increases throughout its lifespan. We also detected a positive correlation between expression constraints (approximated by cis-eQTL properties) and coding constraints (approximated by Ka/Ks) and observed that this correlation might be driven by gene age. To uncover factors associated with the increase in gene-age-related expression constraints, we demonstrated that gene connectivity, gene involvement in complex regulatory networks, gene haploinsufficiency, and the strength of posttranscriptional regulation increase with gene age. We also observed an increase in heritability of gene expression levels with age, implying a reduction of the environmental component. In summary, we show that gene age shapes key gene properties during evolution and is therefore an important component of genome function.
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