Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs
Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs
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DOI：
10.1096/fj.06-6042com
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发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Alexson, Stefan E. H.
中科院分区：
文献类型：
--
作者：
Hunt, Mary C.;Rautanen, Anna;Alexson, Stefan E. H.
维持游离脂肪酸和酰基辅酶a（游离脂肪酸的活化形式）的细胞水平是极其重要的，因为脂质代谢的不平衡会对人体健康造成严重后果。酰基辅酶A （CoA）硫酯酶（ACOTs）将酰基辅酶A水解为游离脂肪酸和CoASH，因此具有调节细胞内这些化合物水平的潜力。我们先前鉴定并鉴定了一个小鼠ACOT基因簇，该基因簇由6个基因组成，它们显然是由基因复制产生的，编码酰基辅酶a硫酯酶，定位于细胞质（ACOT1）、线粒体（ACOT2）和过氧化物酶体（ACOT3 - 6）。然而，相应的人类基因簇只包含三个编码全长硫酯酶蛋白的基因（ACOT1、ACOT2和ACOT4），其中只有一个是过氧化物酶体（ACOT4）。因此，我们开始对人类基因进行表征，我们在这里表明，人类ACOT4蛋白催化三种小鼠过氧化物酶体ACOTs （ACOT3、4和5）的活性，活性于琥珀酰辅酶a和中至长链酰基辅酶a，而ACOT1和ACOT2与相应的小鼠基因具有相似的功能。这些数据有力地表明，人类ACOT4基因通过功能趋同进化获得了三种小鼠基因的功能，这也解释了为什么人类基因的数量出乎意料地少。- Hunt， M. C, Rautanen， A., Westin， M. A. K., Svensson， L. T., Alexson， S. E. H.对小鼠和人类酰基辅酶A硫酯酶（ACOT）基因簇的分析表明，趋同的功能进化导致人类过氧化物酶体ACOT数量减少。
The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important, as imbalances in lipid metabolism have serious consequences for human health. Acyl-coenzyme A (CoA) thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We previously identified and characterized a mouse ACOT gene cluster comprised of six genes that apparently arose by gene duplications encoding acyl-CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2), and peroxisomes (ACOT3 - 6). However, the corresponding human gene cluster contains only three genes (ACOT1, ACOT2, and ACOT4) coding for full-length thioesterase proteins, of which only one is peroxisomal (ACOT4). We therefore set out to characterize the human genes, and we show here that the human ACOT4 protein catalyzes the activities of three mouse peroxisomal ACOTs (ACOT3, 4, and 5), being active on succinyl-CoA and medium to long chain acyl-CoAs, while ACOT1 and ACOT2 carry out similar functions to the corresponding mouse genes. These data strongly suggest that the human ACOT4 gene has acquired the functions of three mouse genes by a functional convergent evolution that also provides an explanation for the unexpectedly low number of human genes. - Hunt, M. C., Rautanen, A., Westin, M. A. K., Svensson, L. T., Alexson, S. E. H. Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs.