Bae Young-An, Cai Guo-Bin, Kim Seon-Hee, Zo Young-Gun, Kong Yoon
Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea.
BMC Evol Biol. 2009 Apr 6;9:72. doi: 10.1186/1471-2148-9-72.
Phospholipid hydroperoxide glutathione peroxidases (PHGPx), the most abundant isoforms of GPx families, interfere directly with hydroperoxidation of lipids. Biochemical properties of these proteins vary along with their donor organisms, which has complicated the phylogenetic classification of diverse PHGPx-like proteins. Despite efforts for comprehensive analyses, the evolutionary aspects of GPx genes in invertebrates remain largely unknown.
We isolated GPx homologs via in silico screening of genomic and/or expressed sequence tag databases of eukaryotic organisms including protostomian species. Genes showing strong similarity to the mammalian PHGPx genes were commonly found in all genomes examined. GPx3- and GPx7-like genes were additionally detected from nematodes and platyhelminths, respectively. The overall distribution of the PHGPx-like proteins with different biochemical properties was biased across taxa; selenium- and glutathione (GSH)-dependent proteins were exclusively detected in platyhelminth and deuterostomian species, whereas selenium-independent and thioredoxin (Trx)-dependent enzymes were isolated in the other taxa. In comparison of genomic organization, the GSH-dependent PHGPx genes showed a conserved architectural pattern, while their Trx-dependent counterparts displayed complex exon-intron structures. A codon for the resolving Cys engaged in reductant binding was found to be substituted in a series of genes. Selection pressure to maintain the selenocysteine codon in GSH-dependent genes also appeared to be relaxed during their evolution. With the dichotomized fashion in genomic organizations, a highly polytomic topology of their phylogenetic trees implied that the GPx genes have multiple evolutionary intermediate forms.
Comparative analysis of invertebrate GPx genes provides informative evidence to support the modular pathways of GPx evolution, which have been accompanied with sporadic expansion/deletion and exon-intron remodeling. The differentiated enzymatic properties might be acquired by the evolutionary relaxation of selection pressure and/or biochemical adaptation to the acting environments. Our present study would be beneficial to get detailed insights into the complex GPx evolution, and to understand the molecular basis of the specialized physiological implications of this antioxidant system in their respective donor organisms.
磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPx）是谷胱甘肽过氧化物酶（GPx）家族中最丰富的亚型，可直接干预脂质的氢过氧化反应。这些蛋白质的生化特性因供体生物而异，这使得对各种类PHGPx样蛋白质的系统发育分类变得复杂。尽管进行了全面分析，但无脊椎动物中GPx基因的进化情况仍 largely未知。
我们通过对包括原口动物物种在内的真核生物基因组和/或表达序列标签数据库进行电子筛选，分离出了GPx同源物。在所有检测的基因组中均普遍发现了与哺乳动物PHGPx基因具有高度相似性的基因。此外，分别从线虫和扁形动物中检测到了类GPx3和类GPx7基因。具有不同生化特性的类PHGPx样蛋白质的总体分布在不同分类群中存在偏差；硒和谷胱甘肽（GSH）依赖性蛋白质仅在扁形动物和后口动物物种中检测到，而硒非依赖性和硫氧还蛋白（Trx）依赖性酶则在其他分类群中分离得到。在基因组组织比较中，GSH依赖性PHGPx基因呈现出保守的结构模式，而其Trx依赖性对应物则表现出复杂的外显子-内含子结构。发现参与还原剂结合的裂解半胱氨酸密码子在一系列基因中被取代。在其进化过程中，维持GSH依赖性基因中硒代半胱氨酸密码子的选择压力似乎也有所放松。由于基因组组织的二分方式，其系统发育树的高度多歧拓扑结构表明GPx基因具有多种进化中间形式。
对无脊椎动物GPx基因的比较分析提供了丰富的证据，支持GPx进化的模块化途径，该途径伴随着零星的扩增/缺失和外显子-内含子重塑。分化的酶学特性可能是通过选择压力的进化放松和/或对作用环境的生化适应而获得的。我们目前的研究将有助于深入了解复杂的GPx进化，并理解这种抗氧化系统在其各自供体生物中特殊生理意义的分子基础。
