The origin and structural evolution ofde novogenes inDrosophila

AbstractAlthough previously thought to be unlikely, recent studies have shown thatde novogene origination from previously non-genic sequences is a common mechanism for gene innovation in many species and taxa. These young genes provide a unique set of candidates to study the structural and functional origination of proteins. However, our understanding of their protein structures and how these structures originate and evolve are still limited, due to a lack of systematic and case studies. Here, we combined high-quality base-level whole genome alignments, bioinformatic analysis, and computational structure modeling to study the origination, evolution, and protein structure of lineage-specificde novogenes. We identified 589de novogene candidates inD. melanogasterthat originated within theDrosophilinaelineage. We found a gradual shift in sequence composition, evolutionary rates, and expression patterns with their gene ages, indicating possible gradual shifts or adaptations of their functions. Surprisingly, we found little overall protein structural changes forde novogenes in theDrosophilinaelineage. We identified a number ofde novogene candidates with protein products that are potentially well-folded, many of which are more likely to contain transmembrane and signal proteins compared to other annotated protein-coding genes. Using ancestral sequence reconstruction, we found that most potentially well-folded proteins are often born folded. Interestingly, we observed one case where disordered ancestral proteins become ordered within a relatively short evolutionary time. Single-cell RNA-seq analysis in testis showed that several youngde novogenes are biased in the early spermatogenesis stage, indicating unneglectable roles of early germline cells in thede novogene origination in testis. This study provides a systematic overview of the origin, evolution, and structural changes ofDrosophilinae-specificde novogenes.