Johann-Friedrich-Blumenbach-Institut, GZMB, University of Göttingen, Justus-von-Liebig-Weg 11, 37077, Göttingen, Germany.
Current address: Institute of Clinical Pharmacology, University Medical Center Göttingen, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
BMC Biol. 2022 Feb 8;20(1):38. doi: 10.1186/s12915-022-01231-4.
Most of the known genes required for developmental processes have been identified by genetic screens in a few well-studied model organisms, which have been considered representative of related species, and informative-to some degree-for human biology. The fruit fly Drosophila melanogaster is a prime model for insect genetics, and while conservation of many gene functions has been observed among bilaterian animals, a plethora of data show evolutionary divergence of gene function among more closely-related groups, such as within the insects. A quantification of conservation versus divergence of gene functions has been missing, without which it is unclear how representative data from model systems actually are.
Here, we systematically compare the gene sets required for a number of homologous but divergent developmental processes between fly and beetle in order to quantify the difference of the gene sets. To that end, we expanded our RNAi screen in the red flour beetle Tribolium castaneum to cover more than half of the protein-coding genes. Then we compared the gene sets required for four different developmental processes between beetle and fly. We found that around 50% of the gene functions were identified in the screens of both species while for the rest, phenotypes were revealed only in fly (~ 10%) or beetle (~ 40%) reflecting both technical and biological differences. Accordingly, we were able to annotate novel developmental GO terms for 96 genes studied in this work. With this work, we publish the final dataset for the pupal injection screen of the iBeetle screen reaching a coverage of 87% (13,020 genes).
We conclude that the gene sets required for a homologous process diverge more than widely believed. Hence, the insights gained in flies may be less representative for insects or protostomes than previously thought, and work in complementary model systems is required to gain a comprehensive picture. The RNAi screening resources developed in this project, the expanding transgenic toolkit, and our large-scale functional data make T. castaneum an excellent model system in that endeavor.
大多数已知的发育过程所需的基因都是通过少数几个研究充分的模式生物的遗传筛选来鉴定的，这些模式生物被认为是相关物种的代表，并且在某种程度上对人类生物学具有信息意义。黑腹果蝇是昆虫遗传学的主要模式生物，虽然许多基因功能在两侧对称动物中都有保守，但大量数据表明，基因功能在亲缘关系更近的群体中发生了进化分歧，例如在昆虫中。缺乏对基因功能保守性与分歧性的定量分析，就不清楚模型系统的数据在多大程度上具有代表性。
在这里，我们系统地比较了果蝇和甲虫中许多同源但不同的发育过程所需的基因集，以量化基因集的差异。为此，我们扩展了我们在赤拟谷盗中的 RNAi 筛选，以涵盖超过一半的编码蛋白基因。然后，我们比较了甲虫和果蝇中四种不同发育过程所需的基因集。我们发现，大约 50%的基因功能在两个物种的筛选中都被鉴定出来，而其余的功能仅在果蝇（10%）或甲虫（40%）中显示，这反映了技术和生物学差异。因此，我们能够为在这项工作中研究的 96 个基因注释新的发育 GO 术语。通过这项工作，我们发表了 iBeetle 筛选的蛹注射筛选的最终数据集，覆盖率达到 87%（13020 个基因）。
我们的结论是，同源过程所需的基因集比广泛认为的要更加多样化。因此，在果蝇中获得的见解可能不如以前认为的那样代表昆虫或原口动物，需要在互补的模型系统中进行研究，以获得全面的认识。在这项工作中开发的 RNAi 筛选资源、不断扩大的转基因工具包以及我们的大规模功能数据使赤拟谷盗成为这一努力的优秀模型系统。
