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Rethinking the Rotting Y Chromosome

Whitehead Seminars for High School Teachers December 8, 2003. Rethinking the Rotting Y Chromosome. SRY. SRY. SRY. X. Y. X. Y. X. Y. Sex Chromosome Evolution: Y as Rotting X. A pair of autosome s. Nature 415, 963 (2002). The future of sex. R. John Aitken and

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Rethinking the Rotting Y Chromosome

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  1. Whitehead Seminars for High School Teachers December 8, 2003 Rethinking the Rotting Y Chromosome

  2. SRY SRY SRY X Y X Y X Y Sex Chromosome Evolution: Y as Rotting X A pair of autosomes

  3. Nature 415, 963 (2002) The future of sex R. John Aitken and Jennifer A. Marshal Graves “The Y chromosome is particularly vulnerable … because it is not a matching partner for the X chromosome, so it cannot retrieve lost genetic information by recombination…. The original Y chromosome contained around 1,500 genes, but during the ensuing 300 million years all but about 50 were inactivated or lost…. At the present rate of decay, the Y chromosome will self-destruct in around 10 million years.”

  4. Spermatogenic Specialization of Y Revealed by Genomic Analyses • DNA sequence of chromosome • Catalog of genes • Y deletions  spermatogenic failure

  5. Euchromatin 23 Mb ≈ 1% of human genome Heterochromatin The MSY, the Male-Specific Region of the Human Y Chromosome p q The MSY differs from other nuclear chromosomes: --specific to one sex --no crossing over

  6. X-transposed (99% X-Y identity) X-degenerate Ampliconic MSY Euchromatin: Three Sequence Classes p q Y-specific repeated blocks (amplicons) comprise one third of MSY’s euchromatic DNA Skaletsky et al., Nature 423: 825 (2003)

  7. TSPY RBMY VCY XKRY CDY HSFY PRY BPY2 DAZ 9 Testis-Specific MSY Gene Families: 60 Members, All Located in Amplicons Skaletsky et al., Nature 423: 825 (2003)

  8. And most of the testis genes are in palindromes...

  9. 1 or more testis genes 1 or more testis genes up to 1.5 million bp Structure of an MSY Palindrome 99.9% - 99.99% identity Skaletsky et al., Nature 423: 825 (2003)

  10. 8 Palindromes and 1 Inverted Repeat Comprise 25% of MSY Euchromatin VCY XKRY CDY HSFY RBMY PRY BPY2 DAZ Yq Yp 8 7 6 5 4 IR2 3 2 1 Skaletsky et al., Nature 423: 825 (2003)

  11. Two Forms of Productive Recombination in Human Y Chromosome Male-specific region Yp Yq 1. X-Y crossing-over in pseudoautosomal regions 2. Y-Y gene conversion in portions of MSY consisting of nearly identical sequence pairs, e.g., palindromes

  12. ~76 protein-coding genes  27 distinct proteins; spermatogenic specialization Old and New Understandings of the MSY genetic wasteland gene-rich palindromes of unprecedented scale + precision full of junky repeats no productive recombination  all genes disintegrating (Muller’s Ratchet) gene conversion  method of preserving gene integrity?

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