Rethinking the Rotting Y Chromosome

Whitehead Seminars for High School Teachers December 8, 2003

Sex Chromosome Evolution: Y as Rotting X

A pair ofautosomes

X

SRY

YX

SRY

YX

SRY

Y

Nature 415, 963 (2002)

The future of sexR. 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 Regionof the Human Y Chromosome

The MSY differs from other nuclearchromosomes:

p q

Euchromatin23 Mb ≈ 1% of human genome Heterochromatin

--specific to one sex --no crossing over

MSY Euchromatin: Three Sequence Classes

p q

Y-specific repeated blocks (amplicons) comprise one third of MSY’s euchromatic DNA

X-transposed (99% X-Y identity)X-degenerateAmpliconic

Skaletsky et al., Nature 423: 825 (2003)

9 Testis-Specific MSY Gene Families:60 Members, All Located in Amplicons

TSPY

VCY

PRY

BPY2

DAZ

RBMY

CDY

XKRY

HSFY

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

up to 1.5 million bp

1 or more testis genes

1 or more testis genes

Skaletsky et al., Nature 423: 825 (2003)

8 Palindromes and 1 Inverted RepeatComprise 25% of MSY Euchromatin

YqYp

HSFY

RBMYPRY

VCY

BPY2

DAZ

CDY

8 6 5 4 3 127 IR2

XKRY

Skaletsky et al., Nature 423: 825 (2003)

Two Forms of Productive Recombination in Human Y Chromosome

1. X-Y crossing-over in pseudoautosomal regions

2. Y-Y gene conversion in portions of MSYconsisting of nearly identical sequence pairs,e.g., palindromes

Yp Yq

Male-specific region

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

spermatogenic specialization27 distinct proteins;

gene-rich palindromes of unprecedented scale + precision

gene conversion method of preserving gene integrity?