'Dissertation Research: Evolution of cis Regulation in Drosophila Maternal Effect Genes'

0073588 Clark Dermitzakis发育早期的基因调控需要一系列复杂的相互作用。在果蝇（Drosophila）中，这些步骤由卵母细胞的蛋白质和信使RNA（mRNA）的母体贡献以及合子和母体基因的转录和翻译调节决定。果蝇胚胎中的前-后（A-P）模式的编排是研究得最好的系统之一。这个系统的复杂性和双重性质的控制（母亲和合子）提供了一个有吸引力的模型，基因调控和母亲的影响动力学的微进化研究。本研究采用实验和理论方法来模拟和解释调控序列的遗传变异模式，以及参与这一过程的基因（bicoid，nanos，caudal，hunchback，pumilio）在物种内和物种间的进化潜力。 将对胚胎表型进行评分，包括黑腹果蝇和相关物种第三染色体纯合系中形态原mRNA和蛋白质的分布和数量。这些基因的上游调控DNA序列（启动子）将被测序并与表型变异相关。我们的目标是确定在A-P图案的剂量依赖性过程中所涉及的基因的自然存在的变化，以测试补偿突变的假设，并在监管区域的进化变化的参数化模型。

0073588Clark & DermitzakisGene regulation during early stages of development entails a complex set of interactions. In the fruit fly (Drosophila), these steps are determined by the maternal contributions of both proteins and messenger RNA (mRNA) to the oocyte as well as by transcriptional and translational regulation of zygotic and maternal genes. The orchestration of anterior-posterior (A-P) patterning in the Drosophila embryo is one of the best-studied systems. The complexity of this system and the dual nature of control (maternal and zygotic) provide an attractive model for microevolutionary studies of gene regulation and maternal effect dynamics. This study uses experimental and theoretical approaches to model and interpret the pattern of genetic variation in regulatory sequences and the evolutionary potential within and between species for genes involved in this process (bicoid, nanos, caudal, hunchback, pumilio). Embryonic phenotypes will be scored, including the distribution and quantities of morphogen mRNA and proteins in third-chromosome-homozygous lines of Drosophila melanogaster and related species. The upstream regulatory DNA sequences (promoters) of these genes will be sequenced and correlated with phenotypic variation. The goals are to identify natural existing variation in the genes involved in the dosage-dependent process of A-P patterning, to test the hypothesis of compensatory mutations, and to parameterize models of evolutionary change in regulatory regions.