Human centromere repositioning "in progress"
Human centromere repositioning "in progress"
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DOI：
10.1073/pnas.0308637101
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发表时间：
2004-04-27
影响因子：
11.1
通讯作者：
Choo, KHA
中科院分区：
文献类型：
--
作者：
Amor, DJ;Bentley, K;Choo, KHA
着丝粒重定位为生殖隔离和物种形成提供了一种潜在的强大进化动力，但其潜在机制仍不明确。一个有吸引力的模型是通过正常着丝粒同时失活以及在迄今为止非着丝粒的染色体位置形成一个新着丝粒，且具有最小的有害影响。我们报道了一个两代人的家族，其中一条4号染色体的着丝粒活性通过在细胞遗传学正常且有丝分裂稳定的核型中形成新着丝粒这一表观遗传方式，被重新定位到4q21.3的一个常染色质位点。原始着丝粒的强烈表观遗传失活通过以下几点得以表明：保留了130万碱基对的着丝粒α -卫星DNA，4号染色体着丝粒近端p臂和q臂序列中未检测到分子改变，以及失活的着丝粒通过大量培养或用组蛋白去乙酰化酶抑制剂曲古抑菌素A处理未能重新激活。新着丝粒结合了功能必需的着丝粒蛋白（CENP - A、CENP - C、CENP - E、CENP - I、BUB1和HIM），尽管与典型着丝粒相比，CENP - A结合和姐妹染色单体 cohesion有所适度降低，这表明可能存在潜在的结构/功能差异。这种假双着丝粒 - 新着丝粒染色体在健康个体中稳定的有丝分裂和减数分裂传递能力，以及新着丝粒活性优先在常染色质位点而非预先存在的α - 卫星DNA区域形成的能力，为人类着丝粒重定位和正在进行的核型进化的内在机制提供了直接证据。我们讨论了这种机制对减数分裂驱动以及灵长类和其他物种进化的更广泛影响。
Centromere repositioning provides a potentially powerful evolutionary force for reproductive isolation and speciation, but the underlying mechanisms remain ill-defined. An attractive model is through the simultaneous inactivation of a normal centromere and the formation of a new centromere at a hitherto noncentromeric chromosomal location with minimal detrimental effect. We report a two-generation family in which the centromeric activity of one chromosome 4 has been relocated to a euchromatic site at 4q21.3 through the epigenetic formation of a neocentromere in otherwise cytogenetically normal and mitotically stable karyotypes. Strong epigenetic inactivation of the original centromere is suggested by retention of 1.3 megabases of centromeric a-satellite DNA, absence of detectable molecular alteration in chromosome 4-centromereproximal p- and q-arm sequences, and failure of the inactive centromere to be reactivated through extensive culturing or treat- ment with histone deacetylase inhibitor trichostatin A. The neocentromere binds functionally essential centromere proteins (CENP-A, CENP-C, CENP-E, CENP-I, BUB1, and HIM), although a moderate reduction in CENP-A binding and sister-chromatid cohesion compared with the typical centromeres suggests possible underlying structural/functional differences. The stable mitotic and meiotic transmissibility of this pseudodicentric-neocentric chromosome in healthy individuals and the ability of the neocentric activity to form in a euchromatic site in preference to a preexisting alphoid domain provide direct evidence for an inherent mechanism of human centromere repositioning and karyotype evolution "in progress." We discuss the wider implication of such a mechanism for meiotic drive and the evolution of primate and other species.