2026-09-20T04:57:23Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/424002022-01-13T07:54:15Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
David C. Page.
Lange, Julian H. (Julian Hendrik)
Massachusetts Institute of Technology. Dept. of Biology.
Massachusetts Institute of Technology. Department of Biology
2008-09-03T15:33:00Z
2008-09-03T15:33:00Z
2008
2008
http://hdl.handle.net/1721.1/42400
237105376
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2008.
Includes bibliographical references.
Mammalian sex chromosomes began diverging from an ordinary pair of autosomes roughly 300 million years ago. Inversions in the evolving Y chromosome sequentially suppressed recombination with the X chromosome. While pseudoautosomal regions in the human Y chromosome still participate regularly in allelic homologous recombination, the male-specific region of the Y (MSY) - the only haploid portion of the nuclear genome - does not. It does, however, engage in non-allelic homologous recombination. In this thesis, I examine modes and outcomes of non-allelic homologous recombination in the MSY. The predictions presented here are based on the double-strand break repair model of recombination between homologous chromosomes, in which a double-strand break (DSB) is the common precursor to crossing over and gene conversion. First, I show that massive MSY-specific palindromes, which maintain arm-to-arm sequence identity via gene conversion, are also the targets of crossing over. Crossover events in palindromes can lead to isochromosome formation and diverse reproductive disorders including sex reversal, male infertility, and Turner syndrome. Second, I demonstrate that a region of the MSY - thought to be recombinationally suppressed with the X chromosome - does undergo extensive X-Y gene conversion. This region encompasses hotspots of ectopic crossover events that lead to X-Y translocations associated with sex reversal syndromes. Although sequences in the MSY engage in productive recombination via gene conversion, alternative resolution of DSBs by crossing over can produce evolutionary "dead ends".
by Julian H. Lange.
Ph.D.
201 p.
eng
Massachusetts Institute of Technology
M.I.T. theses are protected by
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http://dspace.mit.edu/handle/1721.1/7582
Biology.
Diverse outcomes of homologous recombination in the human Y chromosome
Thesis
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<Abstract>Mammalian sex chromosomes began diverging from an ordinary pair of autosomes roughly 300 million years ago. Inversions in the evolving Y chromosome sequentially suppressed recombination with the X chromosome. While pseudoautosomal regions in the human Y chromosome still participate regularly in allelic homologous recombination, the male-specific region of the Y (MSY) - the only haploid portion of the nuclear genome - does not. It does, however, engage in non-allelic homologous recombination. In this thesis, I examine modes and outcomes of non-allelic homologous recombination in the MSY. The predictions presented here are based on the double-strand break repair model of recombination between homologous chromosomes, in which a double-strand break (DSB) is the common precursor to crossing over and gene conversion. First, I show that massive MSY-specific palindromes, which maintain arm-to-arm sequence identity via gene conversion, are also the targets of crossing over. Crossover events in palindromes can lead to isochromosome formation and diverse reproductive disorders including sex reversal, male infertility, and Turner syndrome. Second, I demonstrate that a region of the MSY - thought to be recombinationally suppressed with the X chromosome - does undergo extensive X-Y gene conversion. This region encompasses hotspots of ectopic crossover events that lead to X-Y translocations associated with sex reversal syndromes. Although sequences in the MSY engage in productive recombination via gene conversion, alternative resolution of DSBs by crossing over can produce evolutionary "dead ends".</Abstract>
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