Now in a recent study, published in Nature Ecology & Evolution, Zhao and her team found that about 10 percent of transcription factors (TFs)\u2014including three key TFs\u2014play a major role in regulating de novo gene expression.2 These findings help shed light on the tantalizing mystery of how organisms control new de novo genes.<\/p>\n
To address Weisel\u2019s question, Zhao and her team expanded on earlier work using single-cell RNA sequencing (scRNA-seq) in Drosophila testes, which had provided high-resolution insight into gene expression patterns.3 In their latest analysis, they applied computational methods to scRNA-seq data from the Fly Cell Atlas and identified nearly 500 de novo gene candidates.4 They found that more than 80 percent of these genes exhibited tissue- or cell-type-specific expression, with the majority localized in the testes and associated with germline cells and sensory neurons\u2014suggesting potential roles for these new genes in reproduction or sensory processing.<\/p>\n
The team then asked: Are these de novo genes regulated broadly or are they controlled by some key TFs? From their computational analysis, they found that de novo genes in D. melanogaster were predicted to be regulated by only a few TFs: The top three TFs were Vis, Achi, and Jra (VAJ). \u201c[These TFs] are associated with the meiosis of Drosophila testis, and they basically control roughly a quarter, basically 25 to 28 percent of the de novo gene expression,\u201d explained Zhao. \u201cMeiosis is very important because germ cells need that to produce a sperm for the next generation.\u201d<\/p>\n
![\"Image](\"https:\/\/www.europesays.com\/uk\/wp-content\/uploads\/2025\/08\/li-zhao-laboratory-group-1-m.png\" "\\"Image")
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Zhao and her team investigated the link between de novo gene expression and transcription factors.<\/p>\n
Chris Taggart for The Rockefeller University<\/p>\n
Then, Zhao and her team generated five fruit fly strains with different copy numbers of vis and achi genes, which are involved in meiotic division and differentiation during spermatogenesis, to see whether vis and achi can affect transcription. Indeed, RNA-seq results showed that Vis and Achi upregulated de novo gene expression compared to other testis-biased genes. This expression also correlated with Vis\u2019 mRNA abundance in a linear manner. <\/p>\n
Next, the team sought to see whether these VAJ transcriptional regulations might be linked to de novo gene emergence. They found that these TFs not only regulate and maintain target genes but are also more closely associated with the emergence of younger de novo genes compared to other candidates, suggesting a potential role in their origin.<\/p>\n