Sexual Dimorphism and Evolutionary Innovation in piRNA-Guided Genome Defense

Citation

Chen, Peiwei (2024) Sexual Dimorphism and Evolutionary Innovation in piRNA-Guided Genome Defense. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/9tme-kf22. https://resolver.caltech.edu/CaltechTHESIS:06022024-075040775

Abstract

The genome is a battleground, where different genetic elements vie for inheritance. In particular, selfish genetic elements enhance their own transmission at the expense of host fitness, causing intragenomic conflicts that must be resolved to protect host reproduction. To keep selfish genes in check, animals employ several genome defense mechanisms, including the PIWI-interacting RNA (piRNA) pathway, where small non-coding piRNAs guide PIWI proteins to find complementary RNAs for silencing. While selfish genes are found across the tree of life, they are often sexually dimorphic and lineage-specific. Yet, it remains poorly understood how sex- and lineage-specific selfish genes are tamed by conserved genome defense mechanisms. To address this, I used the piRNA pathway in Drosophila melanogaster as the model system to study sexual dimorphism and evolutionary innovation in genome defense.

In this thesis, I first described my discovery of piRNA sexual dimorphism, which evolved in response to the sex-specific selfish gene landscape. Next, I dissected the genetic basis and molecular mechanisms that underpin piRNA sexual dimorphism, gaining mechanistic insights into how the biological sex modifies the piRNA pathway to tame distinct selfish genes in two sexes. Pivoting to evolutionary innovation, I discovered a novel piRNA locus on the Y chromosome, which I named petrel, that silences the expression of an X-linked host gene, which I named pirate, implicating piRNAs in resolving X-versus-Y sex chromosome conflicts. petrel piRNAs evolved very recently after the split of D. melanogaster from its sibling species, highlighting a recent piRNA innovation against a lineage-specific target. Finally, I described my discovery of a novel genome defense protein factor, which I named Trailblazer, that tames a radically expanded selfish gene family, Stellate. Mechanistically, Trailblazer is a germline transcription factor that, via recent innovation of its DNA-binding domain, up-regulates the expression of two piRNA pathway effectors to quantitatively match Stellate in abundance, indicating a new mode of defense innovation beyond target-specific repressors.

Collectively, my thesis shows that the genomic battleground against selfish genes differs substantially between sexes and across lineages, which selects for distinct innovations in the piRNA pathway to control different selfish genes, thereby safeguarding genome integrity, animal fertility, and species continuity.

Thesis Files