2025-07-14 ロックフェラー大学
Expression pattern of predicted target de novo genes. Novel genes may play significant roles in evolution, biology, and disease.
<関連情報>
- https://www.rockefeller.edu/news/38025-how-new-genes-get-switched-on/
- https://www.nature.com/articles/s41559-025-02747-y
- https://www.pnas.org/doi/10.1073/pnas.2425618122
遺伝子制御ネットワークと新生遺伝子に必須の転写因子 Gene regulatory networks and essential transcription factors for de novo-originated genes
Junhui Peng,Bing-Jun Wang,Nicolas Svetec & Li Zhao
Nature Ecology & Evolution Published:14 July 2025
DOI:https://doi.org/10.1038/s41559-025-02747-y
Abstract
The regulation of gene expression is crucial for the functional integration of evolutionarily young genes, particularly those that emerge de novo. However, the regulatory programmes governing the expression of de novo genes remain unknown. To address this, we applied computational methods to single-cell RNA sequencing data, identifying key transcription factors probably instrumental in regulating de novo genes. We found that transcription factors do not have the same propensity for regulating de novo genes; some transcription factors regulate more de novo genes than others. Leveraging genetic and genomic tools in Drosophila, we further examined the role of two key transcription factors, achintya and vismay, and the regulatory architecture of new genes. Our findings identify key transcription factors associated with the expression of de novo genes and highlight how transcription factors, and possibly their duplications, are linked to the expressional regulation of de novo genes.
転写バーストの比較単細胞解析から、de novo転写産物の起源におけるゲノム構成の役割が明らかになった Comparative single-cell analysis of transcriptional bursting reveals the role of genome organization in de novo transcript origination
UnJin Lee, Cong Li, Christopher B. Langer, +1 , and Li Zhao
Proceedings of the National Academy of Sciences Published:April 30, 2025
DOI:https://doi.org/10.1073/pnas.2425618122
Significance
Understanding the divergence and evolution of novel genes and expression is an essential question in evolutionary biology. However, rapid transcriptomic divergence in tissues such as the testis has significantly hindered comparative single-cell RNA-Sequencing (scRNA-Seq) studies. Here, we provide a strategy—independent of preexisting cell type marker genes—to overcome this barrier. In finding how genome organization influences the evolution of transcriptional bursting dynamics via de novo transcript origination, our results support the cultivator model of de novo gene origination—a model emphasizing the genomic environment in shaping novel gene origination.
Abstract
Spermatogenesis is a key developmental process underlying the origination of newly evolved genes. However, rapid cell type–specific transcriptomic divergence of the Drosophila germline has posed a significant technical barrier for comparative single-cell RNA-sequencing studies. By quantifying a surprisingly strong correlation between species- and cell type–specific divergence in three closely related Drosophila species, we apply a statistical procedure to identify a core set of 198 genes that are highly predictive of cell type identity while remaining robust to species-specific differences that span over 25 to 30 My of evolution. We then utilize cell type classifications based on the 198-gene set to show how transcriptional divergence in cell type increases throughout spermatogenic developmental time. After validating these cross-species cell type classifications using RNA fluorescence in situ hybridization and imaging, we then investigate the influence of genome organization on the molecular evolution of spermatogenesis vis-a-vis transcriptional bursting. We first show altering transcriptional burst size contributes to premeiotic transcription and altering bursting frequency contributes to postmeiotic expression. We then report global differences in autosomal vs. X chromosomal transcription may arise in a developmental stage preceding full testis organogenesis by showing evolutionarily conserved decreases in X-linked transcription bursting kinetics in all examined somatic and germline cell types. Finally, we provide evidence supporting the cultivator model of de novo gene origination by demonstrating how the appearance of newly evolved testis-specific transcripts potentially provides short-range regulation of neighboring genes’ transcriptional bursting properties during key stages of spermatogenesis.
