Miles C, Elgar G, Coles E, Kleinjan D J, van Heyningen V, Hastie N
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13068-72. doi: 10.1073/pnas.95.22.13068.
The pufferfish Fugu rubripes has a genome approximately 7.5 times smaller than that of mammals but with a similar number of genes. Although conserved synteny has been demonstrated between pufferfish and mammals across some regions of the genome, there is some controversy as to what extent Fugu will be a useful model for the human genome, e.g., [Gilley, J., Armes, N. & Fried, M. (1997) Nature (London) 385, 305-306]. We report extensive conservation of synteny between a 1.5-Mb region of human chromosome 11 and <100 kb of the Fugu genome in three overlapping cosmids. Our findings support the idea that the majority of DNA in the region of human chromosome 11p13 is intergenic. Comparative analysis of three unrelated genes with quite different roles, WT1, RCN1, and PAX6, has revealed differences in their structural evolution. Whereas the human WT1 gene can generate 16 protein isoforms via a combination of alternative splicing, RNA editing, and alternative start site usage, our data predict that Fugu WT1 is capable of generating only two isoforms. This raises the question of the extent to which the evolution of WT1 isoforms is related to the evolution of the mammalian genitourinary system. In addition, this region of the Fugu genome shows a much greater overall compaction than usual but with significant noncoding homology observed at the PAX6 locus, implying that comparative genomics has identified regulatory elements associated with this gene.
河豚红鳍东方鲀的基因组比哺乳动物的基因组小约7.5倍，但基因数量相近。尽管已证实在河豚和哺乳动物基因组的某些区域之间存在保守的同线性，但河豚在多大程度上可作为人类基因组的有用模型仍存在一些争议，例如[Gilley, J., Armes, N. & Fried, M. (1997) 《自然》（伦敦）385, 305 - 306]。我们报告了在人类11号染色体的一个1.5兆碱基区域与三个重叠黏粒中的河豚基因组不到100千碱基之间存在广泛的同线性保守。我们的研究结果支持这样一种观点，即人类11号染色体p13区域中的大部分DNA是基因间的。对三个具有截然不同作用的不相关基因WT1、RCN1和PAX6的比较分析揭示了它们结构进化上的差异。人类WT1基因可通过可变剪接、RNA编辑和可变起始位点使用的组合产生16种蛋白质异构体，而我们的数据预测河豚WT1仅能产生两种异构体。这就提出了WT1异构体的进化在多大程度上与哺乳动物泌尿生殖系统的进化相关的问题。此外，河豚基因组的这一区域总体上比平常更为紧凑，但在PAX6基因座观察到显著的非编码同源性，这意味着比较基因组学已鉴定出与该基因相关的调控元件。
