The APL1 immune factor is encoded by a single ancestral gene in most Anopheles species and expanded to three paralogs with distinct function in the Anopheles gambiae complex

Mitri, C.; Bischoff, E.; Eiglmeier, K.; Holm, I.; Dieme, C.; Brito-Fravallo, E.; Raz, A.; Zakeri, S.; Nejad, M. I. K.; Djadid, N. D.; Vernick, K. D.; Riehle, M. M.

doi:10.1101/785089

bioRxiv · 10.1101/785089

The APL1 immune factor is encoded by a single ancestral gene in most Anopheles species and expanded to three paralogs with distinct function in the Anopheles gambiae complex

Mitri, C.·Bischoff, E.·Eiglmeier, K.·Holm, I.·Dieme, C.·Brito-Fravallo, E.·Raz, A.·Zakeri, S.·Nejad, M. I. K.·Djadid, N. D.·Vernick, K. D.·Riehle, M. M.

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Abstract

BackgroundThe recent reference genome assembly and annotation of the Asian malaria vector Anopheles stephensi revealed only one gene encoding the leucine-rich repeat immune factor APL1, while in Anopheles gambiae and sibling Anopheles coluzzii, APL1 factors are encoded by a family of three paralogs. The phylogeny and biological function of the unique APL1 gene in A. stephensi have not yet been specifically examined.\n\nMethodsThe APL1 locus was manually sequenced to confirm the computationally predicted single APL1 gene in A. stephensi, and APL1 evolution within Anopheles was explored by phylogenomic analysis. The single or paralogous APL1 genes were silenced in A. stephensi and A. coluzzii, respectively, followed by mosquito survival analysis, experimental infection with Plasmodium, and expression analysis.\n\nResultsAPL1 is present as a single ancestral gene in most Anopheles including A. stephensi, but has expanded to three paralogs in an African lineage that includes only the Gambiae species complex and Anopheles christyi. Silencing of the unique APL1 copy in A. stephensi results in significant mosquito mortality. Elevated mortality of APL1-depleted A. stephensi is rescued by antibiotic treatment, suggesting that bacteria are the cause of mortality, and that the unique APL1 gene is essential for host survival. Successful Plasmodium development in A. stephensi depends upon APL1 activity for protection from high host mortality, probably caused by exposure to enteric bacteria when parasites cross the midgut epithelial barrier. In contrast, silencing of all three APL1 paralogs in A. coluzzii does not result in elevated mortality, either with or without Plasmodium infection. Expression of the single APL1 gene is regulated by both the Imd and Toll immune pathways, while control by the two pathways is subdivided to different paralogs in the expanded APL1 locus.\n\nConclusionsAPL1 underwent neofunctionalization with both loss and gain of functions concomitant with expansion from a single ancestral gene to three paralogs in one lineage of African Anopheles. The evolution of an expanded APL1 gene family could be a factor contributing to the exceptional levels of malaria transmission mediated by human-feeding members of the Gambiae complex in Africa.

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Mitri, C., Bischoff, E., Eiglmeier, K., Holm, I., Dieme, C., Brito-Fravallo, E., Raz, A., Zakeri, S., Nejad, M. I. K., Djadid, N. D., Vernick, K. D., Riehle, M. M.. 2019-09-27. The APL1 immune factor is encoded by a single ancestral gene in most Anopheles species and expanded to three paralogs with distinct function in the Anopheles gambiae complex. https://doi.org/10.1101/785089

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