A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster.

IF 2.1 3区 生物学 Q3 GENETICS & HEREDITY
Ashley Avila, Lily Paculis, Roxana Gonzalez Tascon, Belen Ramos, Dongyu Jia
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Abstract

Understanding the signaling pathways in which genes participate is essential for discovering the etiology of diseases in humans. The model organism, Drosophila melanogaster, has been crucial in understanding the signaling pathways in humans, given the evolutionary conservation of a significant number of genes between the two species. Genetic screens using Drosophila are a useful way of testing large number of genes to study their function and roles within signaling pathways. We conducted a large-scale genetic screen to identify which human genes cause an alteration in the morphology of the Drosophila eye. The GMR-Gal4 was employed to activate a single UAS-human gene in the eye tissue. In total, we screened 802 UAS-human gene stocks, corresponding to 787 human protein-coding genes, for the ability to influence eye development. We found that overexpression of 64 human genes were capable of disrupting eye development, as determined by phenotypic changes in eye texture, size, shape, bristle morphology, and ommatidia organization. Subsequent analysis revealed that the fly genome encodes proteins that are homologous to a majority of the 64 human genes, raising the possibility that overexpression of these transgenes altered eye development by altering the activity of evolutionarily conserved developmental signaling pathways. Consistent with this hypothesis, a secondary screen demonstrated that overexpression of fly homologs produced phenotypes that mimicked those produced by overexpression of the human gene. Our screening has identified 64 human genes capable of inducing phenotypes in the fly, offering a foundation for ongoing research aimed at understanding functionally conserved pathways across species.

大规模体内筛选,研究人类基因在黑腹果蝇中的作用。
了解基因参与的信号传导途径对于发现人类疾病的病因至关重要。由于黑腹果蝇和人类在进化过程中保留了大量基因,因此黑腹果蝇这一模式生物对了解人类的信号通路至关重要。利用果蝇进行基因筛选是测试大量基因以研究它们在信号通路中的功能和作用的有效方法。我们进行了大规模基因筛选,以确定哪些人类基因会导致果蝇眼睛形态的改变。我们利用 GMR-Gal4 来激活眼组织中的单个 UAS 人类基因。我们总共筛选了 802 个 UAS 人类基因种群(对应于 787 个人类蛋白编码基因),以确定它们是否能够影响眼睛的发育。我们发现,64 个人类基因的过表达能够破坏眼睛的发育,这是由眼睛质地、大小、形状、刚毛形态和膜组织的表型变化决定的。随后的分析表明,苍蝇基因组编码的蛋白质与这 64 个人类基因中的大多数同源,这就提出了一种可能性,即这些转基因的过度表达会通过改变进化上保守的发育信号通路的活性来改变眼睛的发育。与这一假设相一致的是,二次筛选表明,过表达苍蝇同源基因产生的表型与过表达人类基因产生的表型相似。我们的筛选发现了 64 个能够诱导苍蝇表型的人类基因,为正在进行的旨在了解跨物种功能保守通路的研究奠定了基础。
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来源期刊
G3: Genes|Genomes|Genetics
G3: Genes|Genomes|Genetics GENETICS & HEREDITY-
CiteScore
5.10
自引率
3.80%
发文量
305
审稿时长
3-8 weeks
期刊介绍: G3: Genes, Genomes, Genetics provides a forum for the publication of high‐quality foundational research, particularly research that generates useful genetic and genomic information such as genome maps, single gene studies, genome‐wide association and QTL studies, as well as genome reports, mutant screens, and advances in methods and technology. The Editorial Board of G3 believes that rapid dissemination of these data is the necessary foundation for analysis that leads to mechanistic insights. G3, published by the Genetics Society of America, meets the critical and growing need of the genetics community for rapid review and publication of important results in all areas of genetics. G3 offers the opportunity to publish the puzzling finding or to present unpublished results that may not have been submitted for review and publication due to a perceived lack of a potential high-impact finding. G3 has earned the DOAJ Seal, which is a mark of certification for open access journals, awarded by DOAJ to journals that achieve a high level of openness, adhere to Best Practice and high publishing standards.
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