This project addresses three basic questions that concern the evolution of sex chromosomes, and its impact on the rest of the genome: 1) how does the Y chromosome become a genetic junk full of selfish repetitive elements? 2) How does the cell tame such male-specific expansion of selfish elements with small RNAs? 3) How does this arms-race between small RNAs and repeat elements drive the rest of the genome to evolve? Y chromosomes of most species only exist for the function of determining the maleness, with its genetic composition enriched for repetitive elements (sometimes can comprise over 90% of the entire Y chromosome sequence) but very few functional genes. This has been puzzling biologists for long, as the counterpart of Y chromosome, the X chromosome is fully functional and contains thousands of genes, which suggests the ancestor of X and Y chromosomes is a pair of ordinary autosomes. The highly degenerated Y chromosomes have been so widely observed in both plant and animal species, there must be some general evolutionary and molecular driving forces that are yet to be uncovered. The difficulty of tackling this question comes from the fact that most Y chromosomes have undergone at least tens of millions of years of evolution, for example, the human Y chromosome is 170 million years old. They have already become too degenerated with few evolutionary traces left to study. In this project, we are taking advantage of a very young Y chromosome system (termed ‘neo-Y’) aged only 1.5 million years of Drosophila miranda. It formed through fusion of an autosome to the ancestral Y chromosome, thus acquiring the same inheritance pattern as the Y chromosome. My previous studies showed that although most genes still exist on this young Y chromosome, it already has shown clear signatures of degeneration: over two thirds of the Y-linked genes have accumulated mutations that disrupt their protein structure, and a similar proportion of Y-linked genes have reduced their expression levels relative to their X-linked counterparts. And the sequence of this neo-Y has become much more repetitive than the neo-X. We are going to use the cutting-edge technologies of the third-generation sequencing and ChIP-seq to uncover 1) how this young Drosophila Y chromosome has shift its entire gene regulatory landscape from euchromatin to heterochromatin, the latter of which usually only exists in highly repetitive centromere and telomere regions of the genome. The underlying mechanisms have profound implications beyond the Y chromosome evolution alone, as most eukaryotic genomes are organised as intertwined euchromatin and heterochromatin regions, yet their dynamic transitions are unclear for the mechanisms. 2) The second objective involves identifying the responsive changes of small RNA pathways, driven by such expansion of repetitive elements on the Y chromosome, i.e. specifically in males. Small RNA (specifically ‘piRNAs’ and ‘siRNAs’) pathways are several ancient pathways that specifically silence the repeat elements’ activity to guard the integrity of the genome. I will test the hypothesis that the Y chromosome evolution has driven the adaptive changes of small RNA pathway, through birth of new small RNA genes, and/or upregulation of existing small RNA genes. This objective concerns the interaction between the Y chromosome vs. the rest of the genome, i.e. the evolution of Y chromosome is not an isolated event, would rather drive the rest genome to change. 3) The last objective aims to functionally validate the small RNA genes identified from 2). Paradoxically, previous studies showed that small RNAs are mostly deposited by the mother into the embryos, which cannot silence repeat elements from the Y chromosome if there are male-specific sequence changes. Therefore, the evolution of Y chromosome may ultimately drive the female genome to change, so that those repeat elements can be silenced. Overall, the results of these research objectives provide deep insights into our understandings of how male-specific chromosomes evolve, how genome integrity is balanced, and how male and female genomes interact with each other. These questions should be of broad interest to audiences beyond the biological community.
