REGULATION OF SEX-SPECIFIC GENES IN DROSOPHILA

果蝇性别特异性基因的调控

• 批准号: 3271661
• 负责人: THOMAS W CLINE
• 金额: $ 35.95万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3271661
• 关键词: Drosophilidae; RNA splicing; alleles; biological signal transduction; developmental genetics; gel electrophoresis; gene expression; gene induction /repression; gene mutation; genetic manipulation; genetic mapping; genetic promoter element; genetic regulation; genetic transcription; in situ hybridization; molecular cloning; molecular genetics; nucleic acid sequence; polymerase chain reaction; protein structure function; sex chromosomes; sex determination

The aim of this project is to develop a thorough understanding at the genetic and molecular level of holy Drosophila cells translate a two-fold difference in the relative number of X chromosomes (the X/A ratio) into the vast number of qualitative and quantitative differences in gene expression that eventually distinguish males from females. This understanding will provide the basis for meaningful comparisons among different species with respect to their sex determination strategies, and within Drosophila for gene networks that direct different categories of developmental processes. Comparisons such as these should lead to profound insights into how the development of higher organisms is genetically programmed and how that programming evolves. Only with such in depth understanding will it be possible to deal effectively with human genetic diseases. Previous analysis of the target of the Drosophila sex determination signal, the gene Sex-lethal, led to a breakthrough in the analysis of the XIA signal itself with the discovery of the sisterless genes. The sis genes comprise the numerator of this parameter. Only rudimentary information is yet available on sis gene function, but from what little has been learned it is evident that the control of sexual development overlaps in a very significant way with the control of nervous system development. The genes involved in the overlap are relatives of the myc oncogene. By providing a convenient handle for the analysis of myc-family proteins, sex determination may supply clues that are important for understanding some aspects of human cancer. The two sis genes already known will be exhaustively characterized in order to understand specifically how they operate in sex determination and how that function is related to their other functions. The discovery of the sis genes will be exploited thoroughly in order to identify and characterize other genes with related actions, including "denominator" elements of the XIA ratio. The goal is to understand what the XIA signal elements have in common that might account for their involvement in sex determination. Another aspect of the study will draw on the vast amount of information available on the signal target, Sxl, in an attempt to understand specifically how, and thereby why, Drosophila sex determination in the germ line is so different from that in the soma. An incentive for bringing the level of understanding of germline sex determination nearer to that for the soma is the fact that germline sex determination seems to have much more in common than somatic with human sex determination. The third focus of the present study is on the primary sex determination gene itself, Sxl, asking the question of how this complex gene's multiple developmental functions are encoded in its DNA. Sxl information will be deciphered through developmental characterization of Sxl products, and by correlations that emerge between the nature of DNA changes and their functional consequences in an extensive analysis of point mutant alleles and small deletions.

该项目的目的是深入了解 神圣果蝇细胞的遗传和分子水平转化了两倍 X 染色体相对数量的差异（X/A 比率） 基因中大量的质和量的差异 最终区分男性和女性的表达方式。 这 理解将为进行有意义的比较提供基础 不同物种的性别决定策略，以及 果蝇中指导不同类别的基因网络 发展过程。 诸如此类的比较应该会导致 对高等生物的发育过程有深刻的见解 基因编程以及该编程如何进化。 只有这样的 深入了解是否有可能有效地应对人类 遗传疾病。 果蝇性别目标的前期分析 决定信号，性致死基因，导致了 通过发现无姐妹信号来分析 XIA 信号本身 基因。 sis 基因包含该参数的分子。 仅有的 目前尚无关于 sis 基因功能的基本信息，但来自 我们所知甚少，但很明显，对性的控制 发展与控制在很大程度上重叠 神经系统发育。 涉及重叠的基因是 myc 癌基因的亲戚。 通过提供方便的手柄 myc家族蛋白的分析、性别决定可能提供线索 对于理解人类癌症的某些方面很重要。 两人 已知的 sis 基因将被详尽地表征，以便 具体了解它们在性别决定方面的运作方式以及如何 该功能与它们的其他功能相关。 的发现 sis 基因将被彻底利用，以识别和 表征具有相关作用的其他基因，包括“分母” XIA 比率的要素。 目标是了解 XIA 信号的含义 一些共同点可能解释了他们参与性行为的原因 决心。 该研究的另一个方面将利用大量数据 信号目标 Sxl 上可用的信息，试图 具体了解果蝇性行为的方式和原因 种系中的决定与体细胞中的决定有很大不同。 一个 提高对种系性别的理解水平的激励 与体细胞的决定更接近的是，生殖系性别 决心与人类相比，似乎有更多的共同点 性别决定。 本研究的第三个重点是 主要性别决定基因本身，Sxl，询问如何 这个复杂基因的多种发育功能被编码在它的 脱氧核糖核酸。 Sxl信息将通过发育被破译 Sxl 产品的特征，以及之间出现的相关性 DNA 变化的本质及其功能后果 点突变等位基因和小缺失的广泛分析。