Dvornyk Volodymyr, Knudsen Bjarne
Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, 601 N. 30th St., Ste. 6767, Omaha, NE 68131, USA.
Genetica. 2005 Jul;124(2-3):247-54. doi: 10.1007/s10709-005-3146-0.
Cyanobacteria are only prokaryotes known so far to have a circadian system. It may be based either on two (kaiB and kaiC) or three (kaiA, kaiB and kaiC) circadian genes. The homologs of two circadian proteins, KaiB and KaiC, form four major subfamilies (K1-K4) and also occur in some other prokaryotes. Using the likelihood-ratio tests, we studied a rate shift at the functional divergence of the proteins from the different subfamilies. It appears that only two of the subfamilies (K1 and K2) perform circadian functions. We identified in total 92 sites that have significantly different rates of evolution between the clades K1/K2 and K3/K4; 67 sites (15 in KaiB and 52 in KaiC) been evolving significantly slower in K1/K2 than the overall average for the entire sequence. Many critical sites are located in the identified functionally important motifs and regions, e.g. one of the Walker's motif As, DXXG motif, and two KaiA-binding domains of KaiC. There are also 36 sites (approximately 5%) with rate shift between K1 and K2. The rate shift at these sites may be related to the interaction with KaiA. Rate shift analyses have identified residues whose manipulation in the Kai proteins may lead to better understanding of their functions in the two different types of the cyanobacterial circadian system.
蓝藻是目前已知的唯一拥有昼夜节律系统的原核生物。它可能基于两个（kaiB和kaiC）或三个（kaiA、kaiB和kaiC）昼夜节律基因。两种昼夜节律蛋白KaiB和KaiC的同源物形成四个主要亚家族（K1-K4），并且也存在于一些其他原核生物中。我们使用似然比检验研究了来自不同亚家族的蛋白质在功能分化时的速率变化。似乎只有两个亚家族（K1和K2）执行昼夜节律功能。我们总共鉴定出92个位点，这些位点在K1/K2和K3/K4进化枝之间具有显著不同的进化速率；67个位点（15个在KaiB中，52个在KaiC中）在K1/K2中的进化速度明显慢于整个序列的总体平均水平。许多关键位点位于已鉴定的功能重要基序和区域中，例如沃克基序A之一、DXXG基序以及KaiC的两个KaiA结合结构域。在K1和K2之间也有36个位点（约5%）存在速率变化。这些位点的速率变化可能与与KaiA的相互作用有关。速率变化分析已经鉴定出在Kai蛋白中对其进行操作可能有助于更好地理解它们在两种不同类型的蓝藻昼夜节律系统中的功能的残基。
