TY - JOUR
T1 - Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility
AU - Le Page, Daniel P.
AU - Metcalf, Jason A.
AU - Bordenstein, Sarah R.
AU - On, Jungmin
AU - Perlmutter, Jessamyn I.
AU - Shropshire, J. Dylan
AU - Layton, Emily M.
AU - Funkhouser-Jones, Lisa J.
AU - Beckmann, John F.
AU - Bordenstein, Seth R.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) R21 HD086833 and National Science Foundation IOS 1456778 to Seth R.B., National Science Foundation DEB-1501398 and NIH 5T32GM008554 training grant support to D.P.L., NIH T32GM07347 training grant support for J.A.M. to the Vanderbilt Medical Scientist Training Program, and NIH AI081322 to A.M.F. Imaging was performed in part through the use of the Vanderbilt University Medical Center Cell Imaging Shared Resource (supported by NIH grants CA68485, DK20593, DK58404, DK59637, and EY08126).
PY - 2017/3/9
Y1 - 2017/3/9
N2 - The genus Wolbachia is an archetype of maternally inherited intracellular bacteria that infect the germline of numerous invertebrate species worldwide. They can selfishly alter arthropod sex ratios and reproductive strategies to increase the proportion of the infected matriline in the population. The most common reproductive manipulation is cytoplasmic incompatibility, which results in embryonic lethality in crosses between infected males and uninfected females. Females infected with the same Wolbachia strain rescue this lethality. Despite more than 40 years of research and relevance to symbiont-induced speciation, as well as control of arbovirus vectors and agricultural pests, the bacterial genes underlying cytoplasmic incompatibility remain unknown. Here we use comparative and transgenic approaches to demonstrate that two differentially transcribed, co-diverging genes in the eukaryotic association module of prophage WO from Wolbachia strain wMel recapitulate and enhance cytoplasmic incompatibility. Dual expression in transgenic, uninfected males of Drosophila melanogaster crossed to uninfected females causes embryonic lethality. Each gene additively augments embryonic lethality in crosses between infected males and uninfected females. Lethality associates with embryonic defects that parallel those of wild-type cytoplasmic incompatibility and is notably rescued by wMel-infected embryos in all cases. The discovery of cytoplasmic incompatibility factor genes cifA and cifB pioneers genetic studies of prophage WO-induced reproductive manipulations and informs the continuing use of Wolbachia to control dengue and Zika virus transmission to humans.
AB - The genus Wolbachia is an archetype of maternally inherited intracellular bacteria that infect the germline of numerous invertebrate species worldwide. They can selfishly alter arthropod sex ratios and reproductive strategies to increase the proportion of the infected matriline in the population. The most common reproductive manipulation is cytoplasmic incompatibility, which results in embryonic lethality in crosses between infected males and uninfected females. Females infected with the same Wolbachia strain rescue this lethality. Despite more than 40 years of research and relevance to symbiont-induced speciation, as well as control of arbovirus vectors and agricultural pests, the bacterial genes underlying cytoplasmic incompatibility remain unknown. Here we use comparative and transgenic approaches to demonstrate that two differentially transcribed, co-diverging genes in the eukaryotic association module of prophage WO from Wolbachia strain wMel recapitulate and enhance cytoplasmic incompatibility. Dual expression in transgenic, uninfected males of Drosophila melanogaster crossed to uninfected females causes embryonic lethality. Each gene additively augments embryonic lethality in crosses between infected males and uninfected females. Lethality associates with embryonic defects that parallel those of wild-type cytoplasmic incompatibility and is notably rescued by wMel-infected embryos in all cases. The discovery of cytoplasmic incompatibility factor genes cifA and cifB pioneers genetic studies of prophage WO-induced reproductive manipulations and informs the continuing use of Wolbachia to control dengue and Zika virus transmission to humans.
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U2 - 10.1038/nature21391
DO - 10.1038/nature21391
M3 - Article
C2 - 28241146
AN - SCOPUS:85015257725
SN - 0028-0836
VL - 543
SP - 243
EP - 247
JO - Nature
JF - Nature
IS - 7644
ER -