Molecular Interactions and Structural Biology

在给T.H.赫胥黎的一封信中，查尔斯·达尔文有一句著名的评论：“我相信，虽然我不会活着看到，但总有一天，我们将拥有自然界每一个伟大王国的近乎真实的家谱……”现在看来，我们有可能在有生之年实现达尔文的梦想。事实上，进化生物学中最令人兴奋的长期问题之一就是确定什么是“伟大的自然王国”。在过去的几十年里，通过应用分子生物学和基因组技术来理解生命之树，我们发现动物、真菌和植物等王国只代表了生命多样性的一小部分。含核生物（真核生物）之间最深刻的进化分歧涉及一系列被称为“原生生物”的单细胞生物谱系。然而，直到最近，这些古老进化谱系之间的关系仍然是难以捉摸的。在本提案中，我们将使用高通量DNA测序技术来表征十个新描述的单细胞生物的基因组表达部分。通过使用复杂的计算方法将这些数据与几十个更好地表征了生物多样性的生物的类似数据进行比较，我们可以描绘出生命的超级王国。通过这样做，我们将阐明生命进化史上的一些主要“转变”是如何以及何时发生在古代地球上的。

In a letter to T.H. Huxley, Charles Darwin famously commented that: "The time will come, I believe, though I will not live to see it, when we shall have very nearly true genealogical trees of each great kingdom of nature...". It now seems possible that we will realize Darwin's dream within our lifetimes. Indeed, one of the most exciting long-standing problems in evolutionary biology has been to determine what exactly are the 'great kingdoms of nature'. In the last few decades, by applying molecular biology and genomic techniques to understanding the tree of Life we have found that kingdoms such as the animals, fungi and plants represent only a small corner of the diversity of Life. The deepest evolutionary divergences amongst nucleus-containing organisms (eukaryotes) involve a wide array of single-celled organismal lineages called 'protists'. However, the relationships amongst these ancient evolutionary lineages have, until recently, remained elusive. In this proposal we will use high-throughput DNA sequencing technology to characterize the expressed portion of the genomes of ten newly-described single celled organisms. By comparing these data to similar data from dozens of better characterized organisms representing the full breadth of biological diversity using sophisticated computational methods, we can delineate the super-kingdoms of Life. In so doing, we will clarify how and when some of the major 'transitions' in evolutionary history of Life took place on the ancient Earth.