Piergiorge Rafael Mina, de Miranda Antonio Basílio, Guimarães Ana Carolina, Catanho Marcos
Laboratório de Genômica Funcional e Bioinformática, Fiocruz, Instituto Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil.
Laboratório de Biologia Computacional e Sistemas, Fiocruz, Instituto Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil.
Genome Biol Evol. 2017 Jun 1;9(6):1624-1636. doi: 10.1093/gbe/evx119.
Since enzymes catalyze almost all chemical reactions that occur in living organisms, it is crucial that genes encoding such activities are correctly identified and functionally characterized. Several studies suggest that the fraction of enzymatic activities in which multiple events of independent origin have taken place during evolution is substantial. However, this topic is still poorly explored, and a comprehensive investigation of the occurrence, distribution, and implications of these events has not been done so far. Fundamental questions, such as how analogous enzymes originate, why so many events of independent origin have apparently occurred during evolution, and what are the reasons for the coexistence in the same organism of distinct enzymatic forms catalyzing the same reaction, remain unanswered. Also, several isofunctional enzymes are still not recognized as nonhomologous, even with substantial evidence indicating different evolutionary histories. In this work, we begin to investigate the biological significance of the cooccurrence of nonhomologous isofunctional enzymes in human metabolism, characterizing functional analogous enzymes identified in metabolic pathways annotated in the human genome. Our hypothesis is that the coexistence of multiple enzymatic forms might not be interpreted as functional redundancy. Instead, these enzymatic forms may be implicated in distinct (and probably relevant) biological roles.
由于酶催化生物体中几乎所有发生的化学反应，正确识别编码此类活性的基因并对其进行功能表征至关重要。多项研究表明，在进化过程中发生了多个独立起源事件的酶活性部分相当可观。然而，这个主题仍未得到充分探索，到目前为止，尚未对这些事件的发生、分布及其影响进行全面调查。一些基本问题，如类似的酶如何起源、为什么在进化过程中显然发生了如此多的独立起源事件，以及催化相同反应的不同酶形式在同一生物体中共存的原因是什么，仍然没有答案。此外，即使有大量证据表明存在不同的进化历史，一些同功酶仍未被识别为非同源。在这项工作中，我们开始研究人类新陈代谢中非同源自同功酶共存的生物学意义，对在人类基因组注释的代谢途径中鉴定出的功能类似酶进行表征。我们的假设是，多种酶形式的共存可能不能被解释为功能冗余。相反，这些酶形式可能涉及不同的（可能相关的）生物学作用。
