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Evidence for Weak Selective Constraint on Human Gene Expression.

Emily C Glassberg1, Ziyue Gao2,3, Arbel Harpak1,4

  • 1Department of Biology, Stanford University, California 94305.

Genetics
|December 17, 2018
PubMed
Summary
This summary is machine-generated.

Human gene expression shows constraint due to stabilizing selection, particularly against large increases. While rare variants have larger effects, they explain little heritability, allowing for substantial gene-regulatory variation.

Keywords:
Allele-specific expressionGene expressionHeritabilityStabilizing selection

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Area of Science:

  • Human Genetics
  • Evolutionary Biology
  • Genomics

Background:

  • Gene expression variation significantly contributes to human phenotypic diversity.
  • Stabilizing selection on complex traits may impose constraints on gene expression patterns.

Purpose of the Study:

  • To investigate the impact of stabilizing selection on cis-regulatory genetic variation in humans.
  • To understand how selection affects gene expression levels and their variation.

Main Methods:

  • Analysis of expression variation at copy number variants.
  • Utilizing allele-specific expression (ASE) data.
  • Examining cis-eQTLs and loss-of-function variant data.

Main Results:

  • Evidence for selection against substantial increases in gene expression.
  • Identification of selection against smaller-effect variants influencing expression.
  • Singleton variants exhibit larger expression effects but explain minimal heritability.
  • Genes with low loss-of-function variant frequency show depleted cis-eQTLs and allelic imbalance, indicating tighter constraint.

Conclusions:

  • Gene expression levels are under constraint, but this effect is generally weak for most cis-regulatory variants.
  • The constraint permits a high degree of gene-regulatory genetic variation in humans.