Genomic Analyses of New Genes and Their Phenotypic Effects Reveal Rapid Evolution of Essential Functions in Drosophila Development

Abstract

It is a conventionally held dogma that the genetic basis underlying development is conserved in a long evolutionary time scale. Ample experiments based on mutational, biochemical, functional, and complementary knockdown/knockout approaches have revealed the unexpectedly important role of recently evolved new genes in the development of Drosophila. The recent progress in the analyses of gene effects and improvements in the computational identification of new genes, which has led to large sample sizes of new genes, open the door to investigate the evolution of gene essentiality with a phylogenetically high resolution. These advancements also raised interesting issues related to phenotypic effect analyses of genes, particularly of those that recently originated. Here we reported our analyses of these issues, including the dating of gene ages, the interpretation of RNAi data that may confuse false positive/false negative rates, and the potential confounding impact of compensation and developmental effects that were not considered during previous CRISPR knockout experiments. We further analyzed new data from knockdowns of 702 new genes (~66% of total 1,070 Drosophila melanogaster new genes), revealing a similarly high proportion of essential genes from recent evolution, compared to those found in distant ancestors of D. melanogaster. Knockout of a few young genes detected analogous essentiality. Furthermore, our experimentally determined distribution and comparison of knockdown efficiency in different RNAi libraries provided valuable data for general functional analyses of genes. Taken together, these data, along with an improved understanding of the phenotypic effect analyses of new genes, provide further evidence to the conclusion that new genes in Drosophila quickly evolved essential functions in viability during development.