# On the robustness of Bayesian inference of gene flow to intragenic recombination and natural selection

**Authors:** Yuttapong Thawornwattana, Bruce Rannala, Ziheng Yang

PMC · DOI: 10.1093/molbev/msaf327 · Molecular Biology and Evolution · 2025-12-12

## TL;DR

This study examines how accurately Bayesian methods can detect gene flow between species, even when factors like recombination and natural selection are present.

## Contribution

The study reveals that Bayesian inference of gene flow is generally robust, but may produce false positives under specific conditions involving recent divergence and high recombination.

## Key findings

- The Bayesian test of gene flow has very low false positives in most scenarios.
- High recombination rates and recent species divergence can lead to false positives in sister lineage gene flow tests.
- The test of gene flow between nonsister lineages is robust to recombination at all divergence levels.

## Abstract

The multispecies coalescent (MSC) model provides a framework for detecting gene flow using genomic data, including between sister species. However, the robustness of the inference to violations of model assumptions are poorly understood. Here, we use simulation to study the false positive rate of a Bayesian test of gene flow under the MSC with multiple influencing factors including recombination, natural selection, discrete versus continuous gene flow, variable species divergence time, and gene flow involving sister versus nonsister lineages. We find that in almost all scenarios examined the test has very low false positives. However, the test of gene flow between sister lineages may be prone to high false positives in cases of very recent species divergence and very high recombination rate. At low recombination rates, the test is robust to selective sweeps, background selection and balancing selection, although prolonged balancing selection can lead to false signals of gene flow between sister lineages. The impact of excessive recombination on the test of gene flow between sisters may be assessed by using a smaller number of sequences for each species and by considering shorter sequences at each locus. Recent species divergence alone (with no recombination) does not cause false positives in tests of gene flow, contrary to previous claims. The test of gene flow between nonsister lineages is robust to recombination at all divergence levels. Our findings provide guidance for reliable inference of gene flow using coalescent methods and highlight the need for care in conducting and interpreting simulation experiments.

## Full-text entities

- **Genes:** SRPX2 (sushi repeat containing protein X-linked 2) [NCBI Gene 27286] {aka BPP, CBPS, PMGX, RESDX, SRPUL}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}
- **Diseases:** SDLD (MESH:D005099), UDM (MESH:D009759)
- **Chemicals:** BDM (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Cell lines:** -I — Canis lupus familiaris (Dog), Embryonic stem cell (CVCL_JL38)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12759005/full.md

## References

78 references — full list in the complete paper: https://tomesphere.com/paper/PMC12759005/full.md

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Source: https://tomesphere.com/paper/PMC12759005