Kupczok Anne, Bollback Jonathan P
IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
BMC Genomics. 2014 Aug 8;15(1):663. doi: 10.1186/1471-2164-15-663.
CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition.
To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3.
The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here.
CRISPR是一种可能参与宿主 - 寄生虫共同进化的微生物免疫系统。它利用细菌基因组编码的靶序列发挥作用,通过同源依赖性系统干扰入侵的核酸。该系统还需要原间隔序列临近基序(PAMs),即靠近靶序列的短基序,这是I型和II型CRISPR干扰所必需的。在此,我们研究由于逃避识别的选择压力,PAMs在噬菌体基因组中是否减少。
为此,我们分析了两个数据集。首先分析感染所有细菌宿主的噬菌体,随后详细分析感染链球菌属的噬菌体,在该属中对PAMs的了解最为深入。我们使用两种不同的基序代表性不足的衡量方法,以控制密码子偏好和亚基序频率。我们将感染具有特定CRISPR类型物种的噬菌体与感染没有该类型物种的噬菌体进行比较。由于仅研究了已知的PAMs,分析仅限于I - C型和I - E型CRISPR,在链球菌属中仅限于I - C型和II型。我们发现证据表明,感染具有I - C型CRISPR宿主的链球菌噬菌体、感染具有I - E型CRISPR宿主的弧菌噬菌体以及感染具有II - A型(即CRISPR3)宿主的嗜热链球菌噬菌体中存在PAM减少。
在具有CRISPR的宿主的噬菌体中观察到的基序减少可归因于选择而非突变偏好,因为突变偏好应影响所有宿主的噬菌体。这一观察结果表明,CRISPR系统在此处讨论的群体中是有效的。