Laurent A M, Puechberty J, Roizès G
Séquences répétées et centromères humains, Institut de Génétique Humaine UPR 1142, Institut de Biologie, Montpellier, France.
Chromosome Res. 1999;7(4):305-17. doi: 10.1023/a:1009283015738.
A number of questions concerning the evolution and the function of the alpha satellite DNA sequences present at the centromere of all human chromosomes are still open. In this paper, we present data which could contribute to understanding these points. It is shown here that the alphoid sequences within which L1 elements are found are quite divergent from those of the homogeneous alphoid subsets present at each centromere where none has so far been detected. In addition, a number of L1s are detected close to the ends of the alpha satellite blocks. A fairly high proportion exhibit a polymorphism of presence/absence. Strikingly, several L1s localized at a distance from each other are always either present or absent simultaneously. This is interpreted as resulting from intrachromosomal recombination, through distant L1s, leading to deletion of several of them at once together with their surrounding alphoid sequences. The parameters determining which portion of the several megabases of alphoid sequences is actually involved in the centromeric function are not known. From the above data we suggest that the alpha satellite domain within which DNA sequences are recruited to form a centromere is both homogeneous in sequence and uninterrupted by L1s or any other retrotransposons. Conversely, non-centromere competent alphoid sequences would be both divergent and punctuated by scattered L1 elements, particularly at the borders of the alphoid blocks. On the grounds of these data and hypotheses, a model is presented in which it is postulated that accumulation of L1 insertions within a centromere competent alphoid domain is ruining this competence, the consequence being damage to or even loss of the centromere-forming capability of the chromosome. Restoration of fully centromere-forming competence is supposed to occur by two alternative means, either de-novo amplification of a homogeneous and uninterrupted alphoid domain or by unequal crossing over with a homologue harbouring a large competent one. If L1 retrotransposons are acting detrimentally to centromere integrity (for the worst), one must also consider them as having positive consequences on chromosomes by preventing their centromeres from swelling indefinitely by the addition of alphoid sequences (for the best). The data and ideas presented here fit well with those already put forward by Csink and Henikoff (1998) using the example of Drosophila.
关于存在于所有人染色体着丝粒处的α卫星DNA序列的进化和功能，仍有许多问题尚未解决。在本文中，我们提供的数据可能有助于理解这些问题。此处表明，发现含有L1元件的α卫星序列与每个着丝粒处存在的均一α卫星亚群的序列有很大差异，目前在这些着丝粒处尚未检测到L1元件。此外，在α卫星块的末端附近检测到许多L1。相当高比例的L1表现出存在/缺失多态性。令人惊讶的是，彼此相距一定距离定位的几个L1总是同时存在或不存在。这被解释为是由于通过远距离的L1进行染色体内重组，导致它们中的几个以及其周围的α卫星序列同时缺失。决定几个兆碱基的α卫星序列中哪一部分实际上参与着丝粒功能的参数尚不清楚。根据上述数据，我们认为被招募来形成着丝粒的DNA序列所在的α卫星结构域在序列上是均一的，并且不被L1或任何其他逆转座子打断。相反，无着丝粒功能的α卫星序列在序列上会有差异，并且被分散的L1元件打断，特别是在α卫星块的边界处。基于这些数据和假设，我们提出了一个模型，其中假设在有形成着丝粒能力的α卫星结构域内L1插入的积累正在破坏这种能力，其后果是对染色体形成着丝粒的能力造成损害甚至丧失。完全恢复形成着丝粒的能力被认为是通过两种替代方式发生的，要么是均一且不间断的α卫星结构域的从头扩增，要么是与含有大的有功能结构域的同源染色体进行不等交换。如果L1逆转座子对着丝粒完整性有不利作用（最坏的情况），那么人们也必须认为它们对染色体有积极影响，即通过阻止着丝粒因α卫星序列的添加而无限膨胀（最好的情况）。本文提供的数据和观点与Csink和Henikoff（1998年）以果蝇为例已经提出的观点非常吻合。
