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A Slippery Boundary

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A Slippery Boundary COMMENTARY A slippery boundary Andrew G. Clark* Molecular Biology and Genetics, 107 Biotech Building, Cornell University, Ithaca, NY 14853 he Y chromosome has provided ing Y chromosome indicate greater sim- used to freely recombine between the X one of the greatest challenges in ilarity than any comparison between the and Y, but later the PAB moved to the finalizing complete mammalian X and Y chromosomes. As one moves right, leaving all of amelogenin in the genome sequences in part be- rightwards in Fig. 1, the genealogy nonrecombining region where it is to- Tcause of its unusual relationship with day. To date the time of movement of changes, such that some X- and Y- the X chromosome. Part of the Y chro- linked genes are closest neighbors on the pseudoautosomal boundary, Iwase mosome, known as the pseudoautosomal the tree. In this region, the divergence et al. (1) make use of the X vs. Y diver- region, must pair with the complemen- between the X and Y chromosomes gence, and arrive at an estimate of 27–70 tary region on the X chromosome and drops from Ϸ30% to Ϸ10%, and this million years ago. This is after the mam- undergo recombination, so that the re- drop occurs at a transposable element malian radiation, implying that there sulting crossovers stabilize the sex chro- insertion into the second intron of may have been more than one change in mosomes for proper separation during amelogenin. Because of this relatively the pseudoautosomal boundary. Consis- meiosis. The Y chromosome also bears lower X–Y divergence, Iwase et al. pro- tent with this, the location of the PAB, at least one gene that is male-determin- pose that the 3Ј region of amelogenin and gene content of nonrecombining vs. ing, and this region of the Y chromo- pseudoautosomal regions, are widely some must not recombine with the X different among mammals (3). chromosome or sterility or intersexuality These results beg the question what may result. Apart from these two rules, exactly defines the PAB? It is a rather the gene content of the pseudoautoso- remarkable phenomenon that a pair of mal and nonrecombing parts of the Y chromosomes can freely recombine up chromosome are subject to relatively to this point, and then beyond this point weak evolutionary forces. Iwase et al. recombination is absolutely prohibited. (1), in this issue of PNAS, describe a It seems to be a common feature of the remarkable finding that the boundary PAB that a transposable element has between these two portions of the Y inserted there. Although it is plausible chromosome moved relatively recently, that a transposable element insertion and that there appears to be consider- could disrupt pairing, and that once able opportunity for chance to play a pairing is disrupted so is recombination, large role in gene content of these this is not a very satisfying answer be- two very different segments of the Y cause transposable elements insert in chromosome. autosomes all of the time, and chromo- Iwase et al. (1) make a compelling some pairing and recombination is dis- case that the pseudoautosomal boundary rupted in only a minor and local way. It (PAB) previously resided in the second may be useful to consider that it is not intron of the gene encoding amelogenin. only recombination that breaks at the To see how this inference could be PAB, but that well before recombina- made solely based on DNA sequence tion occurs, the pairing between the X comparisons, it will help to refer to Fig. and Y chromosomes may change drasti- 1. Any region of the X and Y chromo- cally at the PAB. In particular, the PAB somes that freely recombines would be almost certainly marks the end of the expected to show divergence levels that region of synapsis between the sex chro- are equal to the level of polymorphism mosomes, a condition necessary for nor- on the X chromosome, or Ϸ1bpper Fig. 1. The location of the PAB is inferred by mal recombination. Despite our igno- 1,000. This is the state of the current Iwase et al. to have been in the amelogenin second rance of what exactly are the features pseudoautosomal region, which falls on intron at approximately the time of radiation of that make a particular part of a chromo- Ј the right end of the diagram. The far mammals. At this time, the 5 end of amelogenin some become a PAB, the sequence was nonrecombining, and so the X and Y copies left portion of the diagram indicates the Ϸ analysis of Iwase et al. (1) does demon- region that has been nonrecombining. became strongly divergent in sequence ( 30%). The gene genealogy for the 5Ј end of amelogenin strate very clearly that it does not re- Amelogenin arrived onto the sex chro- quire anything particularly unusual. The Ϸ shows a monophyletic clustering of the X-linked mosomes 100 million years ago (2), copies among mammals, and a separate monophy- fact that different mammals have such a and remained active on both sex chro- letic clustering of the Y-linked copies. The 3Ј end of diversity of PABs, and that they have mosomes. Iwase et al. (1) show that se- amelogenin recombined up until Ϸ26–70 million moved more than once in our evolution- quences from a variety of mammals in years ago. Before this time, the X and Y chromo- ary history, suggests that there is a large this region form a monophyletic clade somes were recombining, and their sequences component of chance in the setting of for the X chromosome and a distinct were assumed to be homogenized. However, after the PAB boundary. This chance aspect the PAB moved, recombination ceased, and the X monophyletic clade for the Y chromo- Ј leaves open the possibility that it is de- some, suggesting that mammalian spe- and Y copies of the 3 end of amelogenin diverged as well. The gene genealogy of the 3Ј end of termined by some form of chromatin cies have diversified since this region amelogenin thus shows greater similarity of the X remodeling, determined by the proteins became a nonrecombining part of the and Y copies within each mammalian species. Pres- sex chromosomes. This is so because the ently, the PAB is much further to the right, and all tree indicates that comparisons among of amelogenin is in the nonrecombining part of the See companion article on page 5258. mammals in genes on the nonrecombin- sex chromosomes. *E-mail: [email protected]. www.pnas.org͞cgi͞doi͞10.1073͞pnas.0931310100 PNAS ͉ April 29, 2003 ͉ vol. 100 ͉ no. 9 ͉ 4971–4972 Downloaded by guest on October 2, 2021 and RNAs complexed with the DNA, as some. Consistent with this prediction, mosome. Because males do not undergo well as their methylation and acetylation the Y chromosome of Drosophila mela- recombination in Drosophila the neo-Y states. nogaster shows a remarkably strong bias is immediately thrust into a position of Although it seems that chance may toward genes that are necessary for not ever recombining. Recent work by play a role in the location of the PAB, male fertility (6, 7). Overall, the simple Bachtrog and Charlesworth (10) demon- there are evolutionary principles that do evolutionary predictions of what sorts of strate the rapid degeneration of the have an impact on the nature of recom- genes ought to be on which sex chromo- Drosophila miranda neo-Y chromosome bination between the X and the Y. In some do not provide a very satisfying at the molecular sequence level. Y chro- particular, we know that at least some explanation for observed patterns. The mosome degeneration is relevant to of the X and Y chromosomes must re- reasons probably lie in the fact that amelogenin and the wandering PAB combine for normal meiosis, and we there are strong historical effects, that because it shows that whatever genes know that genes involved in male sex we rarely if ever know all of the pleio- are in the nonrecombing portion of the determination must not recombine onto tropic effects of mutations (so our as- Y chromosome are placed in jeopardy. the X. These genes include SRY, SOX9, sumptions about sex-specific effects are Whenever the PAB moves, there must and perhaps several others. At the very not always accurate), and that chance be a period in which the population is least, this implies that the nonrecombin- plays a big role in sex chromosome segregating for the old and new PAB ing portion of the Y must span these composition. location. If the new location goes to fix- genes. In addition, there is a growing The absence of recombination in a ation in the population, by either drift literature on the chromosome distribu- segment of the Y chromosome makes it or selective mechanisms, there may fol- tion of genes with sex-specific effects. In vulnerable to degeneration due to oper- low a time in which the genes that are mammals, it appears that testis-specific ation of Muller’s ratchet. Without re- newly in the nonrecombining portion ESTs tend to be on the X. In Drosoph- combination serving as a source of tem- remain active. The species may run a ila, testis ESTs exhibit a remarkable def- plate for correcting errors on the risk at this time of losing function of icit on the X chromosome (4). A male- nonrecombining Y, mutations accumu- these Y-linked genes. If such a gene is specific favorable mutation would late and may go to fixation. The end vital for survival or fertility, and if loss actually go to fixation faster on the X result is a Y chromosome that has lost of the Y-linked expression is not com- than the Y, leading Rice (5) to predict most of its initial genetic functions (8, pensated by the X-linked copy, then this that male-specific factors ought to clus- 9).
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