The biological significance of DNA content

人类基因组中的蛋白质编码序列数量仅约25，000，占总DNA含量的不到2%。 基因组中绝大多数非编码的生物学意义仍然是个谜。 今天，涉及序列比较的主要举措（例如，ENCODE）正在进行中，以确定所谓的“垃圾DNA”部分是否以及以何种方式可能在监管或其他能力中发挥作用。 更广泛地说，50多年来已经知道总基因组DNA含量对于生物体表型是非中性的。 事实上，据报道，基因组大小与动物和植物的多种性状相关，包括体型、代谢率和发育率。 这些关系被认为是来自基因组大小，细胞大小和细胞分裂速率之间的因果关系，但迄今为止，这还没有得到详细解决。 这里提出的研究将使现代技术承担这个长期存在的问题，并将集中在三个不同的，但相互关联的研究系统。 第一个涉及比较基因组大小和细胞大小从不同的组织和类群，以评估基因组大小细胞大小关系的普遍性。 这将伴随着旨在测试通过影响细胞周期调控将基因组大小与细胞大小联系起来的机制假设的实验工作。 第二项研究包括对脊椎动物的研究，这些脊椎动物的红细胞不含细胞核，但DNA含量对细胞大小的影响持续存在。 第三部分将研究在某些节肢动物组织中发生的大规模基因组增殖的基础和后果。 总的来说，这三项研究将首次回答大规模基因组学中的几个关键问题，并将直接有助于我了解动物基因组中非编码DNA的起源，特征和生物相关性的长期目标。 该计划将产生具有实际意义的生物学家在一系列生物学科工作的数据和方法，除了为学生提供培训的特殊机会。

Protein coding sequences in the human genome number only ~25,000 and constitute less than 2% of the total DNA content. The biological significance of the vast non-coding majority of the genome has remained enigmatic. Today, major initiatives involving sequence comparisons (e.g., ENCODE) are underway to determine whether and in what way portions of so-called "junk DNA" may be functional in regulatory or other capacities. More broadly, it has been known for more than 50 years that total genomic DNA content is non-neutral with respect to organism phenotypes. Indeed, genome size has been reported to correlate with a variety of traits in animals and plants, including body size, metabolic rate, and developmental rate. These relationships are thought to derive from causal links between genome size, cell size, and cell division rate, but to date this has not been addressed in detail. The research proposed here will bring modern technologies to bear on this long-standing question, and will focus on three different but interrelated study systems. The first involves comparisons of genome sizes and cell sizes from a diverse array of tissues and taxa in order to assess the universality of the genome size-cell size relationship. This will be accompanied by experimental work aimed at testing mechanistic hypotheses linking genome size to cell size via influences on cell cycle regulation. The second includes a study of vertebrates whose red blood cells contain no nuclei, but among whom the effects of DNA content on cell size persist. The third will examine the basis and consequences of the massive genome multiplication that occurs within certain arthropod tissues. In total, these three studies will allow several critical questions in large-scale genomics to be answered for the first time, and will contribute directly to my long-term goal of understanding the origins, characteristics, and biological relevance of non-coding DNA within animal genomes. This program will generate both data and methods of practical significance to biologists working in a range of biological disciplines, in addition to providing exceptional opportunities for student training.