Evolution of Homeobox Genes and Mammalian Embryo Development - WCUB, ENWW

胚胎发育调控的变化是复杂生物体进化的主要参与者。同源框基因超类编码DNA结合蛋白，其中许多蛋白在胚胎发育中具有重要功能。我们正在寻找在真兽类哺乳动物的早期胚胎中具有特定表达的同源盒基因；真兽类哺乳动物发育出胎盘并延长怀孕时间，从而导致活产。然而，这些基因在真兽类哺乳动物的不同物种中差异很大，有些差异太大，以至于不再被认为是相关基因，有些基因完全从基因组中消失了。该项目将研究这些胚胎基因(ETCHbox基因)在小鼠和其他啮齿动物中的功能和系统发育分布。在小鼠中，与其他真兽类相比，基因组中保留的ETCHbox基因的子集异常减少，剩余的基因已经扩大。由于这些基因最近才进化，了解它们的功能和它们变化背后的机制将有助于洞察进化上的新基因是如何被纳入新功能的，并有可能增加对真兽类哺乳动物出现背后的机制的理解。BBSRC优先领域：数据驱动生物学：这个项目有一个重要的生物信息学组成部分。在测序分析之后分析大数据集，并使用基因组数据来定义基因的系统发育分布，这项研究的结果在很大程度上是由测序数据的获取和存在推动的。动物研究的替代、改进和减少(3R)：这里描述的方法旨在以最少的活体动物工作对胚胎基因进行功能工作。大部分实验将在已建立的细胞系中进行，这将减少这项研究的任何潜在的伦理问题。

Changes in the regulation of embryonic development are major players in the evolution of complex organisms. The homeobox gene superclass encode DNA-binding proteins, many of which possess an important function in embryogenesis. We are looking at homeobox genes with specific expression in the early embryo of eutherian mammals; mammals that develop a placenta and an extended pregnancy resulting in live birth. These genes, however, are highly variable among different species of eutherian mammal, some so divergent they are no longer recognisable as related genes, and some lost from the genome all together. This project will investigate the function and phylogenetic distribution of these embryonic genes (ETCHbox genes) in mice and other rodents. In mice, the subset of ETCHbox genes retained in the genome is unusually reduced and remaining genes have expanded compared to other eutherians. As these genes have only very recently evolved, understanding their function and the mechanisms behind their variability will provide insight on how evolutionarily new genes are co-opted into new functions, as well as potentially increasing understanding on the mechanisms behind the emergence of eutherian mammals.BBSRC Priority Areas:Data driven biology: This project has a substantial bioinformatic component. Analysing large data sets after sequencing analysis and working with genome data to define the phylogenetic distribution of genes results in this study being largely driven by the acquisition and existence of sequencing data.The replacement, refinement, and reduction in research using animals (3Rs): The methodologies that are described here aim to do functional work on embryonic genes with minimal in vivo animal work. Experiments will be carried out in established cell lines for the most part which reduces any potential ethical issues with this study.