Comparative Analysis Of Completely Sequenced Genomes

细菌、古细菌和真核生物基因组完全测序数据库的快速增长（到2009年中期，已有900多个基因组，还有更多正在进行中）为基因组研究创造了新的机遇和新的挑战。在过去的一年里，我们进行了几项研究，利用基因组信息建立了基因组进化和功能的基本原理。特别是，我们对6,901棵原核基因系统发育树的“森林”进行了全面的比较分析，发现了一致的系统发育信号，特别是在102棵几乎通用的树中，尽管拓扑结构高度不一致，可能是由于水平基因转移。横向转移似乎是随机分布的，并没有掩盖中心趋势。几乎普遍的树在拓扑结构上与许多其他树相似。因此，几乎普遍的树木可能反映了一个重要的集中趋势，尽管它们不能完全代表森林。然而，拓扑一致性主要出现在较浅的树深，而在古细菌和细菌门的辐射水平上突然下降，这表明进化的早期阶段可能不是树状的（生物大爆炸）。在压缩枝状发育或生物大爆炸下的进化模拟更符合压缩枝状发育模型中观察到的树不一致性与系统发育深度之间的相关性。水平基因转移在原核生物中普遍存在：很少有基因树是完全一致的，这使得最初的生命树概念过时了。在古生菌和细菌的整个进化过程中，一个最可能代表垂直遗传的中心趋势是显而易见的，尽管压缩枝发生使主要古生菌和细菌枝之间关系的明确解决变得复杂。此外，为了探索细菌和古细菌的微观进化趋势，我们构建了41个可对齐的紧密基因组簇（atgc）数据集。我们表明，非同义取代率与同义取代率（dN/dS）的中位数之比被用来衡量蛋白质序列的纯化选择压力，这是atgc的一个稳定特征。与先前的研究结果一致，寄生细菌尽管有时因基因丢失而导致基因组急剧缩小，但通常受到相对较弱的净化选择，可能是由于相对较小的有效种群规模和频繁的瓶颈。然而，在任何atgc中都没有发现由强选择压力引起的基因组流线型的证据。相反，尽管具有非常接近的选择压力的各种自由生活的原核生物几乎跨越了整个基因组大小范围，但我们观察到基因组大小以及基因大小与选择压力之间存在显著的正相关关系。此外，我们还研究了序列进化速率与其他基因组特征之间的联系。尽管在原核生物的进化过程中，基因顺序的变化比蛋白质序列的变化快得多，但“重排距离”与氨基酸距离之间存在很强的正相关关系，这表明至少一些导致基因组重排的事件受到与氨基酸序列进化相同类型的选择约束。

The rapidly growing database of completely sequenced genomes of bacteria, archaea and eukaryotes (over 900 genomes available by the middle of 2009 and many more in progress) creates both new opportunities and new challenges for genome research. During the last year, we performed several studies that took advantage of the genomic information to establish fundamental principles of genome evolution and function. In particular, we performed a comprehensive comparative analysis of a 'forest' of 6,901 phylogenetic trees for prokaryotic genes revealed a consistent phylogenetic signal, particularly among 102 nearly universal trees, despite high levels of topological inconsistency, probably due to horizontal gene transfer. Horizontal transfers seemed to be distributed randomly and did not obscure the central trend. The nearly universal trees were topologically similar to numerous other trees. Thus, the nearly universal trees might reflect a significant central tendency, although they cannot represent the forest completely. However, topological consistency was seen mostly at shallow tree depths and abruptly dropped at the level of the radiation of archaeal and bacterial phyla, suggesting that early phases of evolution could be non-tree-like (Biological Big Bang). Simulations of evolution under compressed cladogenesis or Biological Big Bang yielded a better fit to the observed dependence between tree inconsistency and phylogenetic depth for the compressed cladogenesis model.Horizontal gene transfer is pervasive among prokaryotes: very few gene trees are fully consistent, making the original tree of life concept obsolete. A central trend that most probably represents vertical inheritance is discernible throughout the evolution of archaea and bacteria, although compressed cladogenesis complicates unambiguous resolution of the relationships between the major archaeal and bacterial clades. Additionally, in order to explore microevolutionary trends in bacteria and archaea, we constructed a data set of 41 alignable tight genome clusters (ATGCs). We show that the ratio of the medians of nonsynonymous to synonymous substitution rates (dN/dS) that is used as a measure of the purifying selection pressure on protein sequences is a stable characteristic of the ATGCs. In agreement with previous findings, parasitic bacteria, notwithstanding the sometimes dramatic genome shrinkage caused by gene loss, are typically subjected to relatively weak purifying selection, presumably owing to relatively small effective population sizes and frequent bottlenecks. However, no evidence of genome streamlining caused by strong selective pressure was found in any of the ATGCs. On the contrary, a significant positive correlation between the genome size, as well as gene size, and selective pressure was observed, although a variety of free-living prokaryotes with very close selective pressures span nearly the entire range of genome sizes. In addition, we examined the connections between the sequence evolution rate and other genomic features. Although gene order changes much faster than protein sequences during the evolution of prokaryotes, a strong positive correlation was observed between the "rearrangement distance" and the amino acid distance, suggesting that at least some of the events leading to genome rearrangement are subjected to the same type of selective constraints as the evolution of amino acid sequences.