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BRIEF RESEARCH REPORT article

Front. Genet.

Sec. Computational Genomics

This article is part of the Research TopicInsights in Computational Genomics: 2025View all 3 articles

Variance of Ks Distribution Corrects the Bias in the Divergence Caused by the Ancestral Population Size

Provisionally accepted
Mi-Jia  LiMi-Jia Li1Xiao-Xue  LiXiao-Xue Li1Lin-Lin  XuLin-Lin Xu2Bo-Wen  ZhangBo-Wen Zhang1*
  • 1Beijing Normal University, Beijing, China
  • 2Leibniz-Institut fur Naturstoff-Forschung und Infektionsbiologie eV Hans-Knoll-Institut, Jena, Germany

The final, formatted version of the article will be published soon.

Ks distribution, the distribution of the synonymous substitutions, has been widely used to estimate the species divergence using orthologous genes. However, conventional approaches often ignore the underlying bias that species divergence is delayed to average gene divergence by 2Ne generations, where Ne represents the ancestral effective population size, due to the lack of scalable methods for Ne inference. Here, we demonstrate through simulations that Ks distribution variance correlates with Ne, enabling direct estimation of ancestral population parameters from standard Ks data. Leveraging this relationship, we present Tspecies, a framework that corrects divergence time estimates using only substitution rates and Ks distributions, without requiring additional genomic data. Our practical application of Tspecies in Liriodendron has inferred a divergence time between North American and East Asian lineages (1.44 Ma) that align with early Pleistocene glaciation, and a large ancestral Ne (~5.29 × 10^4) consistent with fossil evidence. Our finding reveals the correlation between the variance of Ks distribution and Ne, and develops a computational framework to resolve the bias in Ks based dating by incorporating a readily estimated Ne.

Keywords: Ks distribution, effective population size, Species divergence, Coalescent model, gene divergence, Orthologous gene

Received: 15 Oct 2025; Accepted: 30 Nov 2025.

Copyright: © 2025 Li, Li, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Bo-Wen Zhang

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