生物谷报道：能不能跑马拉松很可能要看你的基因。澳大利亚科学家一项最新的研究表明，基因变异可以广泛地提升人类的肌肉耐力。相关论文9月9日在线发表于《自然—遗传学》上。
人类有两种类型的骨骼肌纤维。一种是快纤维，它不需要氧，直接以糖类作为能源，主要参与需要极限力量和快速反应的运动，比如短跑。另一种是慢纤维，主要以有氧的方式参与需要耐力的运动，比如马拉松。快纤维可以制造一种α辅肌动蛋白（ACTN3），它表明了机体产生快速力量的能力。已有研究证实，从事耐力项目的运动员ACTN3基因的变异频率比其他运动员更高。
领导最新研究的是澳大利亚神经肌肉研究所（Institute for Neuromuscular Research）的遗传学家Kathryn North，她的小组深入研究了ACTN3基因如何影响小鼠的肌肉活力。研究人员发现，缺乏ACTN3功能基因的小鼠会在快纤维中产生大量与有氧代谢相关的酶，且它们的浓度比正常小鼠要高得多。此外，在跑步测试中，变异鼠在精疲力竭之前的跑动距离也比正常鼠多33%，这表明ACTN3基因的变异可以提升耐力。
之前的研究表明，ACTN3基因在不同地域的人类中的变异频率存在差异，非洲平均为10%，而欧洲和亚洲约为50%。为了进一步追溯该基因在人类中的进化历史，研究小组对共96位欧洲、亚洲和非洲人的相关DNA片断进行了测序。结果发现，ACTN3基因的可变性要高于其周围的基因序列，说明这是一个正向自然选择过程。也就是说，ACTN3基因变异一定赋予了现代人（6万年前从非洲迁移到欧洲和亚洲）某种适应性优势。
美国亚利桑那大学的遗传学家Michael Nachmann认为，最新的研究是对ACTN3作用的一个极佳检测，它支持了该基因变异会影响特定运动能力的结论。巴西Paraná大学的进化生物学家Marcio Pie表示，尽管North和同事没有进一步推测ACTN3赋予的进化优势到底是什么，但这将是一个值得继续探讨的有趣问题。（科学网 任霄鹏/编译）
原始出处:
Nature Genetics
Published online: 9 September 2007 | doi:10.1038/ng2122
Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans
Daniel G MacArthur1,2, Jane T Seto1,2, Joanna M Raftery1, Kate G Quinlan1,2, Gavin A Huttley3, Jeff W Hook4, Frances A Lemckert4, Anthony J Kee5, Michael R Edwards6, Yemima Berman1, Edna C Hardeman5, Peter W Gunning2,4, Simon Easteal3, Nan Yang1 & Kathryn N North1,2
More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein -actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that -actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of -actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.
Institute for Neuromuscular Research, Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia.
Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia.
John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 0200, Australia.
Oncology Research Unit, Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia.
Muscle Development Unit, Children's Medical Research Institute, Sydney, New South Wales 2145, Australia.
Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
Correspondence to: Kathryn N North1,2 e-mail: kathryn@chw.edu.au
