Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.
Bioessays. 2010 Jan;32(1):17-25. doi: 10.1002/bies.200900110.
In humans, there are two skeletal muscle alpha-actinins, encoded by ACTN2 and ACTN3, and the ACTN3 genotype is associated with human athletic performance. Remarkably, approximately 1 billion people worldwide are deficient in alpha-actinin-3 due to the common ACTN3 R577X polymorphism. The alpha-actinins are an ancient family of actin-binding proteins with structural, signalling and metabolic functions. The skeletal muscle alpha-actinins diverged approximately 250-300 million years ago, and ACTN3 has since developed restricted expression in fast muscle fibres. Despite ACTN2 and ACTN3 retaining considerable sequence similarity, it is likely that following duplication there was a divergence in function explaining why alpha-actinin-2 cannot completely compensate for the absence of alpha-actinin-3. This paper focuses on the role of skeletal muscle alpha-actinins, and how possible changes in functions between these duplicates fit in the context of gene duplication paradigms.
在人类中，有两种骨骼肌α-辅肌动蛋白，由 ACTN2 和 ACTN3 编码，而 ACTN3 基因型与人类运动表现有关。值得注意的是，由于常见的 ACTN3 R577X 多态性，全世界约有 10 亿人缺乏α-辅肌动蛋白-3。α-辅肌动蛋白是一种古老的肌动蛋白结合蛋白家族，具有结构、信号和代谢功能。骨骼肌α-辅肌动蛋白在大约 2.5 亿至 3 亿年前发生分歧，此后 ACTN3 在快肌纤维中表达受到限制。尽管 ACTN2 和 ACTN3 保留了相当大的序列相似性，但很可能在复制后，功能发生了分歧，这可以解释为什么α-辅肌动蛋白-2不能完全弥补α-辅肌动蛋白-3的缺失。本文重点介绍骨骼肌α-辅肌动蛋白的作用，以及这些重复序列之间功能可能发生的变化如何适应基因复制范例的背景。
