The role of the Hsp90 system in promoting and maintaining genetic complexity

从酵母到人类的生物体的基因组测序项目已经产生了大量关于基因、基因家族和整个生物学进化的信息。这一领域的研究令人惊讶，其中有两个是人类的基因数量之少（比先前预测的少五倍），以及人类和其他生物体之间惊人的相似程度。很明显，基因数量本身并不能解释地球上存在的大量形式。新出现的观点是，这些基因的调控方式在生物学中发挥的作用比以前想象的要大得多。 分子伴侣通过帮助蛋白质折叠成三维结构的过程在调节和调整蛋白质功能中起关键作用。一种这样的伴侣蛋白，90千道尔顿热休克蛋白（Hsp 90），被认为限制了许多蛋白质的三维结构，以调节它们的功能-例如在不同程度上打开和关闭它们。这种活性使Hsp 90在细胞中发挥强大的调节作用，并克服大量蛋白质突变的影响。这对于确保细胞中的蛋白质正常发挥功能很重要，但也允许突变积累，这对进化过程很重要。 该项目旨在直接解决Hsp 90在蛋白质进化和促进功能分化中的作用。我将使用基因的DNA分析和它们编码的蛋白质的结构分析来定义Hsp 90在进化中的作用。

Genome sequencing projects of organisms ranging from yeast to humans have yielded an enormous amount of information regarding evolution of genes, gene families and biology as a whole. Two of the many surprises that have come from this area of research are how few genes humans have (five times fewer than had been previously predicted) and the striking degree of similarity between humans and other organisms. It has become clear that gene numbers alone cannot explain the vast array of forms present on the planet. The emerging view is that how these genes are regulated plays a much larger role in biology than previously thought. Molecular chaperones play a key role in regulating and adjusting protein function by aiding the process of folding into three dimensional structures. One such chaperone protein, the 90 kilodalton heat shock protein (Hsp90), is thought to constrain the three dimensional structure of many proteins to regulate their function - such as turning them on and off to varying degrees. This activity allows Hsp90 to play a powerful regulatory role in cells and to overcome the effects of mutations in a large number of proteins. This is important for ensuring that proteins in cells function normally but also allows mutations to accumulate, which is important for the evolutionary process. This project is designed to directly address the role of Hsp90 in evolution of proteins and facilitating functional divergence. I will employ DNA analysis of genes and structural analysis of the proteins they code for to define the role of Hsp90 in evolution.