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Temporal Patterns of Deleterious Variations: Purifying Selection Across Evolutionary Timescales
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Temporal Patterns of Deleterious Variations: Purifying Selection Across Evolutionary Timescales

Sankar Subramanian
Preprints.org, Vol.21 August 2026
MDPI AG
2026
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Abstract

deleterious variants temporal paerns time dependency dN/dS ratio mitochondrial genome and purifying selection
The nearly neutral theory predicts that mildly deleterious mutations persist transiently within populations before being removed by purifying selection. During the past three decades, studies across diverse taxa, including humans, mammals, viruses, bacteria, and other vertebrates, have consistently reported a temporal paern showing a higher proportion of deleterious variants at short timescales compared to that observed at long timescales. The elevated ratios of nonsynonymous-tosynonymous diversity (dN/dS), enrichment of deleterious variants among rare and young alleles, higher proportions of deleterious mutations in terminal branches of phylogenetic trees, and timedependent variation in molecular evolutionary rates all support the progressive removal of harmful mutations by purifying selection. These observations have important implications for molecular evolution, phylogenetic inference, phylogeography and divergence-time estimation, particularly where recent evolutionary timescales are considered. This review synthesises evidence from population genetics, phylogenomics and molecular evolutionary studies to provide a unified perspective on the temporal dynamics of deleterious mutations. We discuss how these paerns arise from the interaction between genetic drift and purifying selection and their consistency with the predictions of the nearly neutral theory. Finally, we highlight recent advances in modeling purifying selection, particularly in viral evolutionary studies, identify outstanding questions, and propose future research directions for understanding the temporal behaviour of deleterious mutations across genomes and evolutionary timescales.

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