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Abstract Horizontal transfer of genetic material in eukaryotes has rarely been documented over short evolutionary timescales. Here, we show that two retrotransposons,ShellderandSpoink, invaded the genomes of multiple species of themelanogastersubgroup within the last 50 years. Through horizontal transfer,Spoinkspread inD. melanogasterduring the 1980s, while bothShellderandSpoinkinvadedD. simulansin the 1990s. Possibly following hybridization,D. simulansinfected the island endemic speciesD. mauritiana(Mauritius) andD. sechellia(Seychelles) with both TEs after 1995. In the same approximate time-frame,Shellderalso invadedD. teissieri, a species confined to sub-Saharan Africa. We find that the donors ofShellderandSpoinkare likely AmericanDrosophilaspecies from thewillistoni,cardini, andrepletagroups. Thus, the described cascade of TE invasions could only become feasible afterD. melanogasterandD. simulansextended their distributions into the Americas 200 years ago, likely aided by human activity. Our work reveals that cascades of TE invasions, likely initiated by human-mediated range expansions, could have an impact on the genomic and phenotypic evolution of geographically dispersed species. Within a few decades, TEs could invade many species, including island endemics, with distributions very distant from the donor of the TE. 

We show here thatmir-279/996are absolutely essential for development and function of Johnston's organ (JO), the primary proprioceptive and auditory organ inDrosophila. Their deletion results in highly aberrant cell fate determination, including loss of scolopale cells and ectopic neurons, and mutants are electrophysiologically deaf. In vivo activity sensors and mosaic analyses indicate that these seed-related miRNAs function autonomously to suppress neural fate in nonneuronal cells. Finally, genetic interactions pinpoint two neural targets (elavandinsensible) that underlie miRNA mutant JO phenotypes. This work uncovers how critical post-transcriptional regulation of specific miRNA targets governs cell specification and function of the auditory system. 

Suppression of transposable elements (TEs) is paramount to maintain genomic integrity and organismal fitness. InD.melanogaster, theflamencolocus is a master suppressor of TEs, preventing the mobilization of certain endogenous retrovirus-like TEs from somatic ovarian support cells to the germline. It is transcribed by Pol II as a long (100s of kb), single-stranded, primary transcript, and metabolized into ~24–32 nt Piwi-interacting RNAs (piRNAs) that target active TEs via antisense complementarity.flamencois thought to operate as a trap, owing to its high content of recent horizontally transferred TEs that are enriched in antisense orientation. Using newly-generated long read genome data, which is critical for accurate assembly of repetitive sequences, we find thatflamencohas undergone radical transformations in sequence content and even copy number acrosssimulansclade Drosophilid species.Drosophila simulans flamencohas duplicated and diverged, and neither copy exhibits synteny withD.melanogasterbeyond the core promoter. Moreover,flamencoorganization is highly variable acrossD.simulansindividuals. Next, we find thatD.simulansandD.mauritiana flamencodisplay signatures of a dual-stranded cluster, with ping-pong signals in the testis and/or embryo. This is accompanied by increased copy numbers of germline TEs, consistent with these regions operating as functional dual-stranded clusters. Overall, the physical and functional diversity offlamencoorthologs is testament to the extremely dynamic consequences of TE arms races on genome organization, not only amongst highly related species, but even amongst individuals. 

The BEN domain is a recently recognized DNA binding module that is present in diverse metazoans and certain viruses. Several BEN domain factors are known as transcriptional repressors, but, overall, relatively little is known of how BEN factors identify their targets in humans. In particular, X-ray structures of BEN domain:DNA complexes are only known for Drosophila factors bearing a single BEN domain, which lack direct vertebrate orthologs. Here, we characterize several mammalian BEN domain (BD) factors, including from two NACC family BTB-BEN proteins and from BEND3, which has four BDs. In vitro selection data revealed sequence-specific binding activities of isolated BEN domains from all of these factors. We conducted detailed functional, genomic, and structural studies of BEND3. We show that BD4 is a major determinant for in vivo association and repression of endogenous BEND3 targets. We obtained a high-resolution structure of BEND3-BD4 bound to its preferred binding site, which reveals how BEND3 identifies cognate DNA targets and shows differences with one of its non-DNA-binding BEN domains (BD1). Finally, comparison with our previous invertebrate BEN structures, along with additional structural predictions using AlphaFold2 and RoseTTAFold, reveal distinct strategies for target DNA recognition by different types of BEN domain proteins. Together, these studies expand the DNA recognition activities of BEN factors and provide structural insights into sequence-specific DNA binding by mammalian BEN proteins.