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

在发育的早期阶段，基因调控需要一系列复杂的相互作用。在果蝇(果蝇)中，这些步骤是由蛋白质和信使RNA(MRNA)对卵母细胞的母体贡献以及合子和母体基因的转录和翻译调节决定的。在果蝇胚胎中，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控制的双重性(母体和受精卵)为基因调控和母体效应动力学的微进化研究提供了一个有吸引力的模型。这项研究使用实验和理论方法来模拟和解释调控序列中的遗传变异模式，以及参与这一过程的基因在物种内和物种之间的进化潜力(双体、纳米、尾部、驼背、脊椎动物)。将对胚胎表型进行评分，包括形态原mRNA和蛋白质在果蝇及其近缘物种第三染色体纯合子系中的分布和数量。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。其目标是识别参与A-P模式剂量依赖过程的基因的自然存在变异，检验补偿突变的假说，并将调节区进化变化的模型参数化。

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.