A single mutation weakens symbiont-induced reproductive manipulation by reducing the efficiency of deubiquitylation



Wolbachia are mother-transmitted bacteria that infect most insects, making them the most common endosymbionts. Wolbachia achieves this status by manipulating the host’s reproduction. For example, many Wolbachia cause cytoplasmic incompatibility (CI) which kills uninfected embryos. In females, Wolbachia can save ICs, promoting their spread at high frequencies in host populations. The strength of the CI varies by nature from weak to strong. Above all, a strong CI allows Wolbachia biological control strategies in mosquito systems, which protect millions of people against arboviruses. However, theory predicts that natural selection does not work to preserve the genes that cause CI, suggesting that mutations can disrupt it. We show that a single naturally observed mutation weakens CI by reducing desubiquitylation. These findings help to elucidate the molecular basis of reproductive manipulations induced by symbionts.


Animals interact with microbes that affect their performance and fitness, including endosymbionts that reside inside their cells. Maternal transmission Wolbachia bacteria are the most common known endosymbionts, largely due to their manipulation of host reproduction. For example, many Wolbachia cause cytoplasmic incompatibility (CI) which reduces the embryonic viability of the host when Wolbachia-modified sperm fertilize uninfected eggs. Operate called caf Control IC, and a single factor (CA FA) saves him, providing Wolbachia-infected females a fitness benefit. Despite the prevalence of CI in nature, theory indicates that natural selection does not act to maintain CI, which varies widely in strength. Here, we investigate the genetic and functional basis for the variation in CI strength observed in sisters Wolbachia who infects Drosophila melanogaster subgroup hosts. We cloned, sequenced Sanger and expressed caf weak CI directories causing wYak in it Yakuba Drosophila, revealing mutations suspected of weakening the CI compared to the model wMel in D. melanogaster. A single valine-leucine mutation in the deubiquitylation domain (DUB) of wYak cafB counterpart (cidB) suppresses a type CI phenotype in yeast. The same mutation reduces both the efficiency of DUB in vitro and the strength of the transgenic IC in the fly, each approximately twice. Our results match hypomorphic transgenic IC with reduced DUB activity and indicate that deubiquitylation is central to induction of IC in cid systems. We also characterize the effects of other genetic variations by distinguishing wLike Mel caf. Above all, the strength of the CI determines Wolbachia in natural systems and directly influences the efficiency of Wolbachia biological control strategies in transfected mosquito systems. These approaches rely on a strong CI to reduce human disease.


  • Author contributions: research designed by JFB, KVV and BSC; JFB, KVV, DEA and BSC have done research; JFB, DEA and BSC provided new reagents / analytical tools; JFB, KVV, DEA and BSC analyzed the data; JFB and BSC provided financing for the acquisition; BSC coordinated the research; and JFB, KVV, DEA and BSC wrote the article.

  • The authors declare no competing interests.

  • This article is a direct PNAS submission.

  • This article contains additional information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2113271118/-/DCSupplemental.

Data availability

All study data is included in the article and / or additional information.

  • Accepted August 16, 2021.

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