Razin S
Department of Membrane and Ultrastructure Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Indian J Biochem Biophys. 1997 Feb-Apr;34(1-2):124-30.
The mycoplasmas are the smallest and simplest self-replicating organisms, being built of a plasma membrane, ribosomes, and a circular double-stranded DNA molecule-the typical prokaryotic genome. The idea of using mycoplasmas as models for defining in molecular terms the entire machinery of a living cell was raised by Morowitz in 1984. The goal has been to prove the dogma of the completeness of molecular biology, that is, that the logic of life is finite, relatively simple and subject to full exploration. The recent complete sequencing of the genome of the human pathogen Mycoplasma genitalium brings us much closer to achieving this goal. The M. genitalium genome is only 580 kb long and contains only 470 predicted coding sequences(genes), as compared with 1727 in Haemophilus influenzae and about 4000 in E. coli. Thus, M. genitalium is apparently the simplest organism capable of independent life with a minimal set of genes. The drastic economization in genetic information must be associated with the parasitic mode of life of the mycoplasmas. Mycoplasmas evolved by reductive evolution from Gram-positive bacteria with low G + C genomes. During evolution the mycoplasmas have lost the cell wall and many biosynthetic systems involved in synthesis of macromolecule building blocks provided by their host. Thus, the M. genitalium genome carries only one gene involved in amino acid biosynthesis, and very few genes for vitamin and nucleic acid precursors; the lack of genes involved in fatty acid biosynthesis, leads to dependence on exogenous fatty acids, enabling the introduction of controlled variations in membrane acyl chains and the use of mycoplasmas as models in studying membrane fluidity. Moreover, the dependence of mycoplasmas on exogenous cholesterol for growth was exploited to show the role of cholesterol as a buffer of membrane fluidity. The mycoplasma genome carries the minimal set of energy metabolism genes, being content with a restricted supply of ATP needed for their parasitic mode of life. Being limited by a single permeability barrier enabled the saving of a considerable number of transport system genes. Nevertheless, these minimal organisms were shown to carry all the essential genes needed for DNA replication, transcription and translation, but even here gene saving is expressed in a minimal number of rRNA and tRNA genes. A genomic price had been paid to maintain parasitism, so that a significant number of mycoplasmal genes is devoted to adhesins, attachment organelles and variable membrane surface antigens directed towards evasion of the host immune system.
支原体是最小且最简单的自我复制生物体，由质膜、核糖体和一个环状双链DNA分子——典型的原核基因组构成。1984年，莫罗维茨提出用支原体作为模型从分子层面定义活细胞的整个机制。目标是证明分子生物学完备性的信条，即生命的逻辑是有限的、相对简单的且可被充分探索。人类病原体生殖支原体基因组的近期完整测序使我们更接近实现这一目标。生殖支原体基因组仅580 kb长，仅包含470个预测的编码序列（基因），相比之下，流感嗜血杆菌有1727个，大肠杆菌约有4000个。因此，生殖支原体显然是能以最少基因集独立生存的最简单生物体。遗传信息的大幅精简必定与支原体的寄生生活方式相关。支原体由具有低G + C基因组的革兰氏阳性菌通过简化进化而来。在进化过程中，支原体失去了细胞壁以及许多参与合成由宿主提供的大分子构建块的生物合成系统。因此，生殖支原体基因组仅携带一个参与氨基酸生物合成的基因，以及极少的维生素和核酸前体基因；缺乏参与脂肪酸生物合成的基因导致其依赖外源脂肪酸，这使得能够在膜酰基链中引入可控变异，并将支原体用作研究膜流动性的模型。此外，利用支原体对外源胆固醇生长的依赖性来展示胆固醇作为膜流动性缓冲剂的作用。支原体基因组携带最少的能量代谢基因集，满足于其寄生生活方式所需的有限ATP供应。受单一渗透屏障限制使得能节省大量运输系统基因。然而，这些最小的生物体被证明携带DNA复制、转录和翻译所需的所有必需基因，但即便如此，基因精简也体现在rRNA和tRNA基因数量最少。为维持寄生状态付出了基因组代价，以至于大量支原体基因用于黏附素、附着细胞器和可变膜表面抗原，以逃避宿主免疫系统。
