Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases
Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases
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DOI：
10.1093/nar/gkp566
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发表时间：
2009-09-01
影响因子：
14.9
通讯作者：
Burger, Gertraud
中科院分区：
文献类型：
--
作者：
Shen, Yao-Qing;Lang, B. Franz;Burger, Gertraud
酰基辅酶 A 脱氢酶 (ACAD) 是脂肪酸和氨基酸分解代谢的关键酶，形成一个大型的泛分类蛋白质家族，包含至少 13 个不同的亚家族。然而，大多数报道的 ACAD 成员都没有指定亚科，而且人们对亚科的分类分布和进化知之甚少。在大约 210 个物种（真核生物、细菌和古细菌）的完整测序基因组中，我们通过严格的直系同源鉴定结合序列相似性搜索和系统发育来检测 ACAD 亚科。然后，我们构建分类亚科分布图并使用直系同源蛋白质构建系统发育树。亚家族概况提供了仅基于基因组序列对生物体能量来源的无与伦比的洞察，并进一步预测酶底物特异性，从而为目标生化实验产生明确的工作假设。真核 ACAD 亚家族传统上被认为是线粒体蛋白，但我们发现证据表明，在真菌中，一个亚家族位于过氧化物酶体中，并参与独特的 β 氧化途径。最后，我们识别了该家族进化过程中 ACAD 基因的水平转移、复制、丢失和二次获得。通过这些非正统的扩张策略，ACAD家族熟练地利用了大量的脂肪酸和氨基酸——这些策略可能塑造了许多其他古代蛋白质家族的进化史。
Acyl-CoA dehydrogenases (ACADs), which are key enzymes in fatty acid and amino acid catabolism, form a large, pan-taxonomic protein family with at least 13 distinct subfamilies. Yet most reported ACAD members have no subfamily assigned, and little is known about the taxonomic distribution and evolution of the subfamilies. In completely sequenced genomes from approximately 210 species (eukaryotes, bacteria and archaea), we detect ACAD subfamilies by rigorous ortholog identification combining sequence similarity search with phylogeny. We then construct taxonomic subfamily-distribution profiles and build phylogenetic trees with orthologous proteins. Subfamily profiles provide unparalleled insight into the organisms' energy sources based on genome sequence alone and further predict enzyme substrate specificity, thus generating explicit working hypotheses for targeted biochemical experimentation. Eukaryotic ACAD subfamilies are traditionally considered as mitochondrial proteins, but we found evidence that in fungi one subfamily is located in peroxisomes and participates in a distinct beta-oxidation pathway. Finally, we discern horizontal transfer, duplication, loss and secondary acquisition of ACAD genes during evolution of this family. Through these unorthodox expansion strategies, the ACAD family is proficient in utilizing a large range of fatty acids and amino acids-strategies that could have shaped the evolutionary history of many other ancient protein families.