RECONSTRUCTING HOMINID-Y EVOLUTION - X-HOMOLOGOUS BLOCK, CREATED BY X-Y TRANSPOSITION, WAS DISRUPTED BY YP INVERSION THROUGH LINE-LINE RECOMBINATION

The human X and Y chromosomes share many blocks of similar DNA sequenc e, We conducted mapping and nucleotide sequencing studies of extensive , multi-megabase homologies between Yp and Xq21, which do not recombin e during male meiosis, We confirmed and built upon previous evidence t hat 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 appear s to have followed a single transposition of an similar to 4 Mb segmen t from the X to the Y chromosome, These events jointly account for the present arrangement of Yp-Xq21 homologous sequences, Based on Souther n blotting studies of primates and of humans drawn from diverse popula tions, we conclude that both the X-Y transposition and the subsequent, LINE-mediated Yp inversion occurred after the divergence of hominid a nd 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 simi lar to 3-4 million years ago, near the time of emergence of Homo, Comp arative sequencing of the entire human X and Y chromosomes may reveal a succession of transpositions, inversions and other rearrangements un derlying the complex pattern of sequence similarities between the pres ent-day sex chromosomes, With the possible exception of cubitus valgus , phenotypic features of Turner syndrome are absent in individuals mon osomic for Yp-Xq21 homologous sequences, suggesting that most of the c ritical 'Turner genes' are found elsewhere on the X and Y chromosomes.