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Negative Selection

Definition
AI-generated

Negative selection (purifying selection) removes or suppresses alleles that reduce fitness—especially strongly deleterious coding, splice, or highly conserved regulatory changes—keeping them rare in populations.

Topics
Evolutionary genetics
Related
Loss-of-Function Variant Minor Allele Frequency (MAF) Natural Selection

Why it matters in GWAS

Constraint metrics (e.g. loss-of-function intolerance, conservation scores) prioritize coding and regulatory variants for follow-up. Rare-variant association and gene-based tests explicitly model purifying selection on the mutational spectrum; background selection can distort neutral diversity near functional elements and affect calibration of some scans.

Example usage

"The missense variant fell in a highly constrained exon, consistent with strong negative selection against similar changes."

Loss-of-Function Variant Minor Allele Frequency (MAF) Natural Selection Positive Selection Selection Pressure
Related-term network

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Node order. The current term is first. Next come every page linked from Related terms, in the same top-to-bottom order as that list. Then new terms appear in two-hop layers: for each of those direct neighbors (in that same order), their related terms are appended if not already listed. A third pass does the same for two-hop nodes. The walk stops when a fixed maximum number of nodes is reached.

References

  • Eyre-Walker A, Keightley PD. (2007). The distribution of fitness effects of new mutations. Nat Rev Genet.
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