Whitehead Seminars for High School Teachers
December 8, 2003
Rethinking the
Rotting Y Chromosome
Sex Chromosome Evolution:
Y as Rotting X
SRY
A pair of
autosomes
X Y
SRY
X Y
SRY
X Y
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.”
Spermatogenic Specialization of
Y Revealed by Genomic Analyses
• DNA sequence of chromosome
• Catalog of genes
• Y deletions  spermatogenic failure
The MSY, the Male-Specific Region
of the Human Y Chromosome
Euchromatin
23 Mb ≈ 1% of human genome
Heterochromatin
p
q
The MSY differs from other nuclear
chromosomes:
--specific to one sex
--no crossing over
MSY Euchromatin: Three Sequence Classes
X-transposed (99% X-Y identity)
X-degenerate
Ampliconic
p
q
Y-specific repeated blocks (amplicons)
comprise one third of MSY’s euchromatic DNA
Skaletsky et al., Nature 423: 825 (2003)
9 Testis-Specific MSY Gene Families:
60 Members, All Located in Amplicons
TSPY
RBMY
VCY
XKRY
CDY
HSFY
PRY
BPY2
DAZ
Skaletsky et al., Nature 423: 825 (2003)
And most of the
testis genes are in palindromes...
Structure of an MSY Palindrome
99.9% - 99.99% identity
1 or more testis genes
1 or more testis genes
Skaletsky et al., Nature 423: 825 (2003)
up to 1.5 million bp
8 Palindromes and 1 Inverted Repeat
Comprise 25% of MSY Euchromatin
VCY
XKRY
HSFY
RBMY
PRY
CDY
BPY2
DAZ
Yq
Yp
8
76
Skaletsky et al., Nature 423: 825 (2003)
5 4
IR2 3
2
1
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
Old and New Understandings of the MSY
genetic wasteland
full of junky repeats
no productive recombination
 all genes disintegrating
(Muller’s Ratchet)
~76 protein-coding genes 
27 distinct proteins;
spermatogenic specialization
gene-rich palindromes of
unprecedented scale + precision
gene conversion  method of
preserving gene integrity?