Eukaryotic genomes harbor a variety of evolutionarily ?selfish? genetic elements (SGEs) that seek to ensure their transmission at the expense of their hosts. SGEs fall into two broad classes: those that distort fair Mendelian transmission (e.g., meiotic drive elements) and those that over-replicate relative to the host genome (e.g., transposable elements, or TEs). TEs have been especially successful, e.g. constituting ~20% of the fruitfly (Drosophila melanogaster) genome, ~45% of the human genome, and ~85% of the maize genome. Their presence and activity in hosts are major causes of deleterious mutation, genome instability, and infertility. Eukaryotes have, in response, evolved elaborate surveillance and suppression mechanisms to detect and mitigate the deleterious effects of TEs, respectively. The resulting conflicts between TEs and their hosts potentiate molecular evolutionary arms races that can cause rapid population genetic divergence and speciation? the process by which new species originate. Therefore, understanding the genetics, molecular biology, and evolution of TE interactions with the host defense apparatus are major goals of genome biology. Here we propose to investigate the molecular coevolution of two well-studied retrotransposable elements, R1 and R2, with two closely related fruitfly host species, Drosophila simulans and D. mauritiana. These fruitfly species are reproductively isolated by multiple genetic incompatibilities that cause sterility or lethality in their hybrid progeny. We have discovered that one of these genetic incompatibilities involves the aberrant de-repression of R1 and R2 retrotransposons in somatic tissues and a syndrome of phenotypic defects? including lethality, delayed egg-to-adult development time, and disrupted morphological development? characteristic of compromised ribosomal function. Importantly, R1 and R2 insert site-specifically into, and thus disrupt, an appreciable proportion of the linearly arrayed, multicopy ribosomal genes. While R1 and R2 are normally epigenetically silenced, our preliminary findings reveal that hybrid genotypes fail to suppress R1 and R2 (but not other TEs), resulting in the expression of inserted, non-functional ribosomal RNAs. We have therefore identified the species-specific regulation of two well-characterized TEs that reside in a well-characterized genomic locus, the ribosomal RNA gene array.
The aims of our research project are to combine genetics, molecular biology, cytology, next- generation sequencing, and evolutionary genomics methods to determine the genes, molecular mechanisms, and evolutionary forces involved in the coevolution of R1 and R2, with their host species. Our research promises to shed light on how TEs evolve to evade host surveillance and/or suppression, how hosts genomes evolve in response, and how the essential, multicopy ribosomal RNA genes are epigenetically regulated to optimize transcription of TE insertion-free gene copies.
The genomes of most organisms, including humans, harbor a variety of so-called selfish genetic elements that enhance their own transmission by subverting normal reproduction and, in doing so, often contributing to host infertility and developmental problems. We will identify host genes and mechanisms that mediate species-specific suppression of two selfish genetic elements? two retrotransposable ?copy-and-paste? elements that insert into the ribosomal DNA locus? and study how their evolution has contributed to the origin of new species. This research will provide novel insights into how host genomes mitigate the effects of selfish genetic elements and, incidentally, cause one species to split into different, reproductively incompatible descendant species. !