Dybvig K, Sitaraman R, French C T
Department of Comparative Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13923-8. doi: 10.1073/pnas.95.23.13923.
The hsd genes of Mycoplasma pulmonis encode restriction and modification enzymes exhibiting a high degree of sequence similarity to the type I enzymes of enteric bacteria. The S subunits of type I systems dictate the DNA sequence specificity of the holoenzyme and are required for both the restriction and the modification reactions. The M. pulmonis chromosome has two hsd loci, both of which contain two hsdS genes each and are complex, site-specific DNA inversion systems. Embedded within the coding region of each hsdS gene are a minimum of three sites at which DNA inversions occur to generate extensive amino acid sequence variations in the predicted S subunits. We show that the polymorphic hsdS genes produced by gene rearrangement encode a family of functional S subunits with differing DNA sequence specificities. In addition to creating polymorphisms in hsdS sequences, DNA inversions regulate the phase-variable production of restriction activity because the other genes required for restriction activity (hsdR and hsdM) are expressed only from loci that are oriented appropriately in the chromosome relative to the hsd promoter. These data cast doubt on the prevailing paradigms that restriction systems are either selfish or function to confer protection from invasion by foreign DNA.
肺炎支原体的hsd基因编码限制酶和修饰酶，这些酶与肠道细菌的I型酶具有高度的序列相似性。I型系统的S亚基决定了全酶的DNA序列特异性，并且是限制反应和修饰反应所必需的。肺炎支原体染色体有两个hsd位点，每个位点都包含两个hsdS基因，并且是复杂的位点特异性DNA倒位系统。在每个hsdS基因的编码区域内至少有三个发生DNA倒位的位点，以在预测的S亚基中产生广泛的氨基酸序列变异。我们表明，由基因重排产生的多态性hsdS基因编码了一系列具有不同DNA序列特异性的功能性S亚基。除了在hsdS序列中产生多态性外，DNA倒位还调节限制活性的相变产生，因为限制活性所需的其他基因（hsdR和hsdM）仅从相对于hsd启动子在染色体中方向合适的位点表达。这些数据对限制系统要么是自私的，要么是起到保护作用以防止外来DNA入侵的主流范式提出了质疑。
