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bioRxiv · 10.64898/2026.03.16.712127

A simple test demonstrates that many prokaryotic accessory genes are adaptive.

Eyre-Walker, Y. C.·Conradsen, C.·Vos, M.·Eyre-Walker, A.
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Abstract

Bacterial genomes often contain many genes that are only present in a subset of strains, the so-called accessory genes. Whether these genes are adaptive, neutral or deleterious remains contentious. Here we introduce a simple test to differentiate between these possibilities. If an accessory gene is adaptive then the sequence of the gene should be conserved, and the ratio of non-synonymous to synonymous diversity,{pi} n/{pi}s, should be less than one. In contrast, if the gene is neutral or deleterious, selection should not conserve the gene sequence, and{pi} n/{pi}s should equal one. We apply this test to accessory genes in Escherichia coli and Staphylococcus aureus, two highly divergent bacterial species with a large and a small pangenome respectively. We find{pi} n/{pi}s<1 for genes at all frequencies in both species demonstrating that many are adaptive. We estimate that at least 75% of all the accessory genes are maintained by selection in the two species that we have analysed, equating to thousands of adaptive accessory genes in both species, a substantial increase on previous estimates. Significance statementMany bacterial genes are found in only a subset of the strains of a bacterial species. These are referred to as accessory genes. Whether, accessory genes are adaptive, allowing certain strains to inhabit particular niches, remains a highly contentious question. In this paper we introduce a simple test of whether accessory genes are adaptive and show that >75% of them are, in two highly divergent bacterial species. This radically alters our view of this type of genetic variation and bacterial evolution.

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Eyre-Walker, Y. C., Conradsen, C., Vos, M., Eyre-Walker, A.. 2026-03-18. A simple test demonstrates that many prokaryotic accessory genes are adaptive.. https://doi.org/10.64898/2026.03.16.712127

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