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