Schwartz A, Chan D C, Brown L G, Alagappan R, Pettay D, Disteche C, McGillivray B, de la Chapelle A, Page D C
Howard Hughes Medical Institute, Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
Hum Mol Genet. 1998 Jan;7(1):1-11. doi: 10.1093/hmg/7.1.1.
The human X and Y chromosomes share many blocks of similar DNA sequence. We conducted mapping and nucleotide sequencing studies of extensive, multi-megabase homologies between Yp and Xq21, which do not recombine during male meiosis. We confirmed and built upon previous evidence that a Yp inversion had occurred during evolution: a single contiguous segment of Xq21 is homologous to two non-contiguous segments of Yp. We precisely defined and sequenced the inversion breakpoints, obtaining evidence that the inversion was mediated by recombination between LINE-1 elements in otherwise non-homologous regions. This inversion appears to have followed a single transposition of an approximately 4 Mb segment from the X to the Y chromosome. These events jointly account for the present arrangement of Yp-Xq21 homologous sequences. Based on Southern blotting studies of primates and of humans drawn from diverse populations, we conclude that both the X-Y transposition and the subsequent, LINE-mediated Yp inversion occurred after the divergence of hominid and chimp lineages but before the radiation of extant human populations. This evolutionary scenario is consistent with our finding of 99.3 +/- 0.2% nucleotide identity between the X and Y chromosomes within the transposed region, which suggests that the transposition occurred approximately 3-4 million years ago, near the time of emergence of Homo . Comparative sequencing of the entire human X and Y chromosomes may reveal a succession of transpositions, inversions and other rearrangements underlying the complex pattern of sequence similarities between the present-day sex chromosomes. With the possible exception of cubitus valgus, phenotypic features of Turner syndrome are absent in individuals monosomic for Yp-Xq21 homologous sequences, suggesting that most of the critical 'Turner genes' are found elsewhere on the X and Y chromosomes.
人类X和Y染色体有许多相似的DNA序列片段。我们对Yp和Xq21之间广泛的、多兆碱基的同源性进行了图谱绘制和核苷酸测序研究，这些区域在男性减数分裂期间不发生重组。我们证实并扩展了先前的证据，即在进化过程中发生了Yp倒位：Xq21的一个连续片段与Yp的两个不连续片段同源。我们精确地定义并测序了倒位断点，获得的证据表明该倒位是由非同源区域中的LINE-1元件之间的重组介导的。这种倒位似乎是在一个约4 Mb的片段从X染色体单次转座到Y染色体之后发生的。这些事件共同解释了Yp-Xq21同源序列的当前排列。基于对灵长类动物和来自不同人群的人类的Southern印迹研究，我们得出结论，X-Y转座和随后的由LINE介导的Yp倒位都发生在人类和黑猩猩谱系分化之后，但在现存人类群体辐射之前。这种进化情况与我们在转座区域内X和Y染色体之间发现的99.3±0.2%的核苷酸同一性一致，这表明转座发生在大约300万至400万年前，接近智人出现的时间。对整个人类X和Y染色体进行比较测序可能会揭示一系列转座、倒位和其他重排，这些重排构成了当今性染色体之间复杂的序列相似性模式的基础。除了肘外翻可能的例外情况外，Yp-Xq21同源序列单体的个体没有特纳综合征的表型特征，这表明大多数关键的“特纳基因”位于X和Y染色体的其他位置。
