Biological Recombination
In genomes, in genes, in proteins
Preface: Fu et al ‘02
• Transposon? Ac and Ds?• Retrotransposon?• Genetic length vs. physical length?• Recombination higher among genes?
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What I’ll Cover
• Reasons and mechanisms• Rates and sites• Within-protein
QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
Why recombine?
Cui bono?QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
Kondrashov’s Theory of Sex
Kondrashov, A. S., Nature 336, 435-441 (1988).
X
X
X
X
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DSB model
See Szostak et al, Cell 33, 25-33 (1983).
DSB model
Limited crossover Full crossover
Transposons: cut and paste
Davies et al, Science 289 (2000)
Retrotransposons: copy and paste
gag prot DR334
DR334 int rt
Yeast Ty element, 6 kb
cDNA
mRNA
Measuring recombination
1911: Alfred Sturtevant invents the map unit
A story every graduate studentshould remember.
Where does recombination occur?
Thuriaux, P., Nature 268, 460-462 (1977).
Rates in gene-rich regions
Fu et al, PNAS 99:2, 1082-1087 (2002)
… ~100kb transposon nest …
0.06 cM, 108 kb
Ac6058
0.32 cM6.5 kb
0.25 cM, 11.6 kb
0.24 cM6.7 kb
Ac6087
Ac6067
bz
Ac2094
Variability of Recomb. Rates
McKim, K., Ann. Rev. Gen. 36, 205-32 (2002).
Recombination inside genes
• Alternative splicing• Mobile introns• And a gene that will blow your mind.
Alternative splicing
Roberts et al, Curr. Op. Chem. Bio. 6, 375-383 (2002).
Intron mobility
• Some introns “home”• Introns are gained and lost
constantly• Introns define exons
– Are exons domains?– Selective pressure?
jingwei: the Frankengene
Llopart et al, PNAS, 99:12, 8121-8126 (2002).
Acknowledgments
• Recombination group and Frances• Chris Adami
• Shoulders of various giants
And there’s more…
• Immune-system domain shuffling• Inteins