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Selection-dependent and Independent Generation of CRISPR/Cas9-mediated Gene Knockouts in Mammalian Cells

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Published on: June 16, 2017

Early-life viability selection targets deleterious mutations in exons.

Rebecca S Chen¹, Carl D Soulsbury², Kees van Oers³

¹Department of Evolutionary Population Genetics, Faculty of Biology, Bielefeld University, 33501 Bielefeld, Germany.

Current Biology : CB

|November 19, 2025

Summary

Deleterious mutations impact fitness, but selection varies by life stage and genomic region. Early life selection primarily targets conserved sites in exons, not just inbreeding effects.

Keywords:

coding mutations conservation genetic load inbreeding depression life-history evolution mutation load predicted deleterious mutations viability selection

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Following the Dynamics of Structural Variants in Experimentally Evolved Populations

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Published on: February 3, 2023

Area of Science:

Evolutionary biology
Conservation biology
Genomics

Background:

Deleterious mutations are crucial for evolutionary and conservation biology.
Empirical studies often use inbreeding as a proxy for mutation load, neglecting heterozygous effects.
Functional heterogeneity and temporal variation in selection are often overlooked.

Purpose of the Study:

To investigate how deleterious mutations affect viability selection across different life stages and genomic regions.
To move beyond inbreeding proxies and assess mutation load directly.
To understand the dynamic nature of selection on mutations.

Main Methods:

Whole-genome resequencing of the black grouse (Lyrurus tetrix).
Prediction of deleterious mutations using evolutionary conservation and functional predictions.
Quantification of viability selection across chicks, yearlings, and adults.

Main Results:

Viability selection is strongest in early life stages (chicks).
Early-life selection predominantly targets deleterious mutations at evolutionarily conserved sites, particularly in exons.
Selection regimes are dynamic, varying across life stages and genomic contexts.

Conclusions:

Fitness effects of deleterious mutations are not constant or uniform across the genome.
Selection regimes shift dynamically with life-history stages and genomic locations.
Findings refine understanding of evolutionary dynamics and inform conservation strategies using genomic fitness indicators.