Lynch Vincent J
Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06520-8106, USA.
Yale J Biol Med. 2009 Jun;82(2):53-66.
Transgenic animal models have played an important role in elucidating gene functions and the molecular basis development, physiology, behavior, and pathogenesis. Transgenic models have been so successful that they have become a standard tool in molecular genetics and biomedical studies and are being used to fulfill one of the main goals of the post-genomic era: to assign functions to each gene in the genome. However, the assumption that gene functions and genetic systems are conserved between models and humans is taken for granted, often in spite of evidence that gene functions and networks diverge during evolution. In this review, I discuss some mechanisms that generate functional divergence and highlight recent examples demonstrating that gene functions and regulatory networks diverge through time. These examples suggest that annotation of gene functions based solely on mutant phenotypes in animal models, as well as assumptions of conserved functions between species, can be wrong. Therefore, animal models of gene function and human disease may not provide appropriate information, particularly for rapidly evolving genes and systems.
转基因动物模型在阐明基因功能以及发育、生理、行为和发病机制的分子基础方面发挥了重要作用。转基因模型非常成功，已成为分子遗传学和生物医学研究中的标准工具，并正被用于实现后基因组时代的一个主要目标：确定基因组中每个基因的功能。然而，基因功能和遗传系统在模型与人类之间是保守的这一假设常常被视为理所当然，尽管有证据表明基因功能和网络在进化过程中会发生分歧。在这篇综述中，我将讨论一些导致功能分歧的机制，并重点介绍一些最近的例子，这些例子表明基因功能和调控网络会随着时间而发生分歧。这些例子表明，仅基于动物模型中的突变表型对基因功能进行注释，以及对物种间功能保守性的假设可能是错误的。因此，基因功能和人类疾病的动物模型可能无法提供适当的信息，尤其是对于快速进化的基因和系统而言。
