The evolution of genomes at large

实现对基因组大规模特征的详细理解是21世纪生物科学的首要目标之一。尽管全基因组测序的迅速兴起理所当然地在科学界内外引起了相当大的关注，但分析特定DNA序列和寻找模式生物中的蛋白质编码基因只是“比较基因组学”的一个方面。尽管基因组学的其他领域最近取得了巨大的进展，但对基因组一些最基本特性（如大小和组成）的变异的解释仍然难以捉摸。例如，即使经过半个多世纪的持续研究，为什么不同动物基因组中包含的DNA数量（即基因组大小）相差超过3300倍，仍然是一个未解之谜。这里概述的研究计划旨在通过直接处理基因组大小变化的长期谜题来推进我们对大规模基因组进化的理解。具体来说，这里提出的研究将从几个主要方面阐明这一重要问题：1)通过提高从多种动物类群中获得基因组大小数据的效率和准确性，2)通过填补目前哺乳动物、鸟类和鱼类基因组大小数据集的一些主要空白，3)通过对昆虫基因组大小进行首次大规模调查，4)通过测试关于基因组大小与细胞大小、代谢和发育等特征之间关系的一些特定假设。通过与新兴生物多样性倡议的联系以及使用新的DNA定量技术，我的实验室将准备以前所未有的规模生成基因组大小数据。从更大的角度来看，这些重要的初步研究将代表一个更大的“基因组多样性”项目的种子，我将努力在新的安大略省生物多样性研究所内培养这个项目。总的来说，除了回答一些关于基因组进化的最基本的问题外，该计划还将为从事一系列生物学学科的生物学家提供具有实际意义的数据。

Achieving a detailed understanding of the large-scale features of genomes represents one of the premier objectives of twenty-first century biological science.  Though the rapid rise of complete genome sequencing has justifiably garnered considerable attention both within and outside the scientific community, analyses of specific DNA sequences and the search for protein-coding genes in model organisms represent only one aspect of "comparative genomics".   Despite tremendous recent progress in other areas of genomics, explanations for variation in some of the most basic properties of genomes, such as size and composition, remain elusive.  For example, even after more than half a century of continuous study, it remains an unresolved puzzle why the amount of DNA contained within different animal genomes (i.e., genome size) ranges more 3,300-fold.  The research program outlined here seeks to advance our understanding of large-scale genome evolution by dealing directly with the long-standing enigma of genome size variation.  Specifically, the research proposed here will shed light on this important issue in several major ways: 1) by improving the efficiency and accuracy by which genome size data can be obtained from a diverse array of animal taxa, 2) by filling some major gaps in the current genome size datasets for mammals, birds, and fishes, 3) by performing the first large-scale survey of genome sizes in insects, and 4) by testing some specific hypotheses about the relationships between genome size and such features as cell size, metabolism, and development.  Through linkages with emerging biodiversity initiatives and with use of novel DNA quantification technology, my lab will be poised to generate genome size data on an unprecedented scale.  In larger terms, these important initial studies will represent the seed of a much larger program in "genomic diversity" that I will strive to cultivate within the new Biodiversity Institute of Ontario.  Overall, this program will provide data of practical significance to biologists working in a range of biological disciplines, in addition to answering some of the most fundamental questions about the evolution of genomes at large.