Defining the functional landscapes of metazoan genomes

“为什么有些基因组非常大，而另一些却相当紧凑？”，“这些‘垃圾’在我们的基因组中做什么？”以及“四肢、鳍和脸是如何发育和进化的？”这是2005年7月1日《科学》杂志确定的125个科学大问题中的3个。要回答这些问题，以及其他问题，需要对来自不同动物的基因组——生命之书——进行逐字比较。然而，查看每个字母是否被保留或替换并不能说明全部情况，因为我们还需要考虑字母是否被添加或删除。总的来说，字母的保存或插入或删除可以突出生命之书中构成所有动物基本生物学基础的部分，以及指定物种之间差异的其他部分。《科学》杂志提出的第四个大问题是“新技术将在多大程度上降低（基因组）测序成本？”这个问题正开始得到解答：测序很快就会变得非常便宜，以至于生物学家感兴趣的许多（如果不是全部的话）动物的基因组将在2010年完成测序。我们的研究小组已经开始分析人类、小鼠、大鼠、狗和鸡的基因组，其首要目标是精确定位人类基因组中与人类健康有关的字母。我们现在希望考虑来自动物王国的所有可用基因组，以解决科学中的重大问题。在这个项目中，我们将在这些基因组中找到编码蛋白质的基因，以及其他不编码蛋白质的基因。然后，我们将计算蛋白质编码基因和非蛋白质编码基因在指定(a)动物的古代生物学和(b)区分动物进化树分支的生物学方面的相对贡献。由于我们不能回答所有其他有趣的问题，我们将在互联网上提供全面的信息，让来自世界各地的其他生物学家从中受益。

'Why are some genomes really big and others quite compact?', 'What is all that 'junk' doing in our genomes?', and 'How do limbs, fins, and faces develop and evolve?' These are 3 of the 125 Big Questions in Science, identified by Science magazine on 1 July 2005. To answer these, and other questions, requires a letter-by-letter comparison of genomes -- the books-of-life -- from very different animals. Seeing whether each letter is conserved, or else replaced, does not however tell the full story, since we also need to consider whether letters are added or deleted. Taken together, the conservation, or the insertion or deletion, of letters can highlight those parts of the books-of-life that underlie the basic biology of all animals, and others that specify the differences between species. A fourth Big Question, named by Science, is 'How much will new technologies lower the cost of [genome] sequencing?' This is beginning to be answered: sequencing will soon become so cheap that many, if not all, of the animals of interest to biologists will have their genomes sequenced by 2010. Our group has already served an apprenticeship analysing the genomes of humans, mice, rats, dogs, and chickens, with an over-arching aim of pinpointing the letters of the human genome that contribute to human health. We now wish to consider all available genomes from across the animal kingdom in order to address the Big Questions in Science. In this project, we shall find genes that encode protein, and others that do not, in each of these genomes. We then will calculate the relative contributions of protein-coding genes and non-protein-coding genes in specifying (a) the ancient biology of animals, and (b) the biology that distinguishes branches of the animal evolutionary tree. As we cannot answer all other interesting questions, we will provide comprehensive information on the internet to allow other biologists from around the world to benefit from them.