Evolutionary changes in germ granule mRNA content are driven by multiple mechanisms inDrosophila

Abstract

AbstractThe co-packaging of mRNAs into biomolecular condensates called germ granules is a conserved strategy to post-transcriptionally regulate mRNAs that function in germline development and maintenance. InD. melanogaster, mRNAs accumulate in germ granules by forming homotypic clusters, aggregates that contain multiple transcripts from a specific gene. Nucleated by Oskar (Osk), homotypic clusters inD. melanogasterare generated through a stochastic seeding and self-recruitment process that requires the 3’ UTR of germ granule mRNAs. Interestingly, the 3’ UTR belonging to germ granule mRNAs, such asnanos(nos), have considerable sequence variations amongDrosophilaspecies. Thus, we hypothesized that evolutionary changes in the 3’ UTR influences germ granule development. To test our hypothesis, we investigated the homotypic clustering ofnosandpolar granule component(pgc) in fourDrosophilaspecies and concluded that homotypic clustering is a conserved developmental process used to enrich germ granule mRNAs. Additionally, we discovered that the number of transcripts found innosand/orpgcclusters could vary significantly among species. By integrating biological data with computational modeling, we determined that multiple mechanisms underlie naturally occurring germ granule diversity, including changes innos,pgc,osklevels, and/or homotypic clustering efficacy. Finally, we found that thenos3’ UTR from different species can alter the efficacy ofnoshomotypic clustering, resulting in germ granules with reducednosaccumulation. Our findings highlight the impact that evolution has on the development of germ granules and may provide insight into processes that modify the content of other classes of biomolecular condensates.