The ink4a/arf locus evolution in primates:: Characterization of three ARF sequences
The ink4a/arf locus evolution in primates:: Characterization of three ARF sequences
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DOI：
10.1089/104454904322964760
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发表时间：
2004-03-01
影响因子：
3.1
通讯作者：
Ladeveze, V
中科院分区：
文献类型：
--
作者：
Di Tommaso, A;Soler, C;Ladeveze, V
人类ink 4a/arf基因座编码两种细胞周期调节蛋白-细胞周期蛋白依赖性激酶抑制剂（p16（ink 4a））和p53激活剂（ARF）-通过使用交替的第一外显子。这种基因组组织在真核生物中是独特的，使用不同的阅读框架获得两种不同的蛋白质。小鼠或负鼠与人类ARF之间的差异非常大，而蛋白质具有相同的核仁定位和功能。为了进一步了解ARF在不同环境中的相对重要性，我们在这里描述了12种不同灵长类动物ARF外显子1 β的特征。我们在研究的物种（猴子、猿和人类）中没有发现任何多态性。这些序列非常相似，与人类序列相比具有很少的氨基酸取代。当人类、猪、大鼠或小鼠、鸡外显子1 β序列之间存在如此低的保守性时，在灵长类动物中发现如此高的保守性是很奇怪的。更令人惊讶的是，我们在所有人序列中观察到在位置31处的苏氨酸，而丙氨酸总是存在于其他序列中。我们认为，当辐射人类/猿出现或之后，苏氨酸的选择发生。此外，检测到的修饰可能在ARF与其他蛋白质之间的不同相互作用中发挥作用，以稳定或不稳定这些复合物。
The human ink4a/arf locus encodes two cell cycle regulatory proteins-the cyclin-dependent kinase inhibitor (p16(ink4a)), and the p53 activator (ARF)-through the use of alternative first exons. This genomic organization is unique in eukaryotes, with two different proteins obtained using different reading frames. The divergence between mouse or opossum and human ARF is very high, whereas proteins have the same nucleolar localization and function. To gain further insights into the relative importance of ARF in different settings, we characterized here the exon 1beta of ARF in 12 different species of primates. We did not find any polymorphism in studied species (monkeys, apes, and humans). These sequences are very similar, with few amino acids substitutions compared to the human sequence. It is strange to rind such a high degree of conservation among primates when there is such a low degree of conservation between the human pig, rat, or mouse, chicken exon 1beta sequences. More surprisingly, we observe a threonine at position 31 in all human sequences, whereas an alanine is always present in other sequences. We suggest that when the radiation human/simian appeared or after, a selection of threonine occurred. Moreover, the modifications detected could play a role in different interactions between ARF and other proteins to stabilize or not these complexes.