Phylogenomic and functional analyses of ZAD-ZNF transcription factors in Drosophila

Abstract

Evolutionarily dynamic, essential genes challenge the long-held dogma that essential genes are highly conserved. Although these genes are scientifically compelling, only a handful of studies have identified evolutionarily young, rapidly evolving genes and determined their function. Examining the process by which a young gene becomes essential can shed light on how gene origin and evolution drive biological diversity. I focused my studies on ZAD-ZNF genes, which encode the most abundant yet dynamic class of transcription factors in Drosophila melanogaster and related species. I found significant evidence of genetic innovation via both gene turnover and positive selection in ZAD-ZNF genes. Although many ancient, conserved ZAD-ZNFs are essential for viability or fertility, I unexpectedly found that genetically innovating ZAD-ZNFs are more likely to be essential. I took a candidate locus approach to understand the cause of ZAD-ZNF dynamism, focusing on one cluster of five ZAD-ZNFs. Through cytological analyses, I found that three of the five ZAD-ZNFs localize to heterochromatin, a rapidly evolving compartment of the nucleus. I focused my functional characterization on Nick Nack, a rapidly evolving, evolutionarily young, essential ZAD-ZNF within the cluster. I found that Nick Nack is necessary for larval development and for maintenance of heterochromatin. This work identifies the seemingly paradoxical finding that rapidly evolving ZAD-ZNF genes can be essential for development in Drosophila and suggests that rapidly changing heterochromatin functions may underlie the diversification of this gene family.