UC Berkeley

Y chromosomes are fascinating parts of the genome. In XY determination species, they specify the male sex and to do so, they influence a wide variety of molecular and cellular processes. Furthermore, since the Y is restricted to the male lineage, they undergo unique evolutionary trajectories resulting in gene-poor and repeat-rich chromosomes. This begs the question of how Y chromosomes can elicit drastic biological differences such as differences between sexes and differences between individuals. In my dissertation, I leveraged the Y chromosomes of two Drosophila species to address this fundamental question.

Males often die earlier than females in XY species and recent studies have shown that the Y chromosome may play a role in this sex-specific phenomenon. Intriguingly, repetitive DNA such as transposable elements (TEs) show increased expression over aging, suggesting that the Y’s repetitive nature can contribute to this observation. I study sex-specific aging by leveraging the well-assembled genome of D. miranda, whose males have a very large young Y chromosome (neo-Y). The neo-Y was recently formed through a fusion between an autosome and a Y chromosome and therefore contains both genes and TEs. Using chromatin immunoprecipitation followed by sequencing (ChIP-Seq) and RNA-Seq, I showed that D. miranda males age faster than females possibly because of gene activity on the Y that also increases overall TE expression. Therefore, ineffective repression of deleterious elements both on and off the Y can explain the differences in aging.

While many Y’s are degenerate, they can still vary in size within a population. The D. pseudoobscura Y especially has long been known to harbor dramatic size variation in the wild. I show that the 24Mb size difference between a large Y chromosome variant and a small variant is due to a handful of recently active TEs using cytological and sequencing approaches. These same TEs are also implicated in the size variation of a related species, D. affinis. Consistent with previous work, these Y chromosomes produce subtle changes in male lifespan and gene expression. Interestingly, I find that males bearing the large Y variant have higher expression of large Y-abundant TEs compared to males bearing the small Y. Thus, the very large Y chromosome variant of D. pseudoobscura was recently formed through highly active TEs and that these particular TEs have the propensity to also amplify in other species.

Gene content on the Y was previously believed to be sparse but advances in sequencing have countered these old notions. In particular, Y chromosomes have been implicated in intragenomic conflicts with the X chromosome via gene amplification. I inspect the genomes and gene annotations of three D. pseudoobscura Y variants to investigate gene content evolution within a population. I find that the D. pseudoobscura Y is not a gene desert. In fact, it contains many gene families with hundreds of gene copies and not all variants contain the same families or copy numbers. Expression of these Y chromosome genes reveal that select genes are testis-expressed with sperm-related functions while others are involved in chromatin regulation. Therefore, Y chromosome gene content is highly dynamic and Y chromosome genes may play a role in wide-reaching biological processes.