Eisen J A, Heidelberg J F, White O, Salzberg S L
The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.
Genome Biol. 2000;1(6):RESEARCH0011. doi: 10.1186/gb-2000-1-6-research0011. Epub 2000 Dec 4.
Whole-genome comparisons can provide great insight into many aspects of biology. Until recently, however, comparisons were mainly possible only between distantly related species. Complete genome sequences are now becoming available from multiple sets of closely related strains or species.
By comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure. Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment. The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species. Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well.
The most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication. The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution.
全基因组比较能够为生物学的诸多方面提供深刻见解。然而,直到最近,比较主要仅在亲缘关系较远的物种之间才可行。如今,多组亲缘关系密切的菌株或物种的完整基因组序列已可获取。
通过分别将霍乱弧菌、肺炎链球菌和结核分枝杆菌最近完成的基因组序列与亲缘关系密切的物种——大肠杆菌、化脓性链球菌和麻风分枝杆菌的基因组序列进行比较,我们发现了细菌基因组结构一个不同寻常且此前未观察到的特征。每对物种之间保守序列(包括DNA和蛋白质)的散点图呈现出一种独特的X形模式,我们将其称为X比对。这些比对的关键特征是它们围绕复制起点和终点具有对称性;也就是说,特定保守特征(DNA或蛋白质)距复制起点(或终点)的距离在亲缘关系密切的物种对之间是保守的。在一些基因组中也发现了具有统计学意义的X比对,这表明旁系同源特征围绕复制起点也具有对称性。
产生X比对最可能的机制涉及大型染色体倒位,这种倒位使基因组序列围绕复制起点对称地反转。在许多物种对之间发现这些X比对表明,围绕起点的染色体倒位是细菌基因组进化的一个共同特征。