Covariance in RNA

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Covariance in RNA
ref
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Covariance
TyC
anticodon
3acc
D-stem
Mij Sfxixjlog2fxixj/(fxifxj) M0 to 2
bits xbase type xixj
see Durbin et al p. 266-8.
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Mutual Information
ACUUAU M1,6 S fAU log2fAU/(fAfU)... CC
UUAG x1x6 GCUUGC
4.25log2.25/(.25.25)2 UCUUGA i1 j6
M1,2 4.25log2.25/(.251)0 Mij
Sfxixjlog2fxixj/(fxifxj) M0 to 2 bits xbase
type xixj
see Durbin et al p. 266-8.
See Shannon entropy, multinomial Grendar
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Covariance in lab evolution
Second Passage
First Passage
?trp/?tyrA pair of genomes shows the best
co-growth Reppas, Lin Church Shendure et
al. Accurate Multiplex Polony Sequencing of an
Evolved Bacterial Genome(2005) Science 3091728
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Sequence monitoring of evolution(optimize
transport drug resistance)
Sequence
Reppas, Lin Church
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Co-evolution of mutual biosensors/biosynthesisseq
uenced across time within each time-point

• Independent lines of
• TrpD TyrD co-culture
• 5 OmpF (pore large,hydrophilic gt small)
• 42R-gt G,L,C, 113 D-gtV, 117 E-gtA
• 2 Promoter (cis-regulator)
• -12A-gtC, -35 C-gtA
• 5 Lrp (trans-regulator)
• 1bD, 9bD, 8bD, IS2 insert, R-gtL in DBD.
• Heterogeneity within each time-point .

Shendure J, Porreca GJ, et al. 2005. Accurate
multiplex polony sequencing of an evolved
bacterial genome. Science 309 1728-32
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Flux ratios at each branch point yields optimal
polymer composition for replication
x,y are two of the 100s of flux dimensions
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Non-optimal evolves to optimal
Ibarra et al. Nature. 2002 Nov
14420(6912)186-9. Escherichia coli K-12
undergoes adaptive evolution to achieve in silico
predicted optimal growth.
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Comparative genome sequencing of E. coli allows
observation of bacterial evolution on a
laboratory timescale.
Herring et al 2006 Nat. Gen 381406
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The Amino-acid Mutational Spectrum of Human
Genetic Disease.
Vitkup,D, Sander,C, Church,GM (2003) Genome Biol.
4 R72.
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Prediction of deleterious human alleles
Shamil Sunyaev, Vasily Ramensky, Ina Koch, Warren
Lathe III, Alexey S. Kondrashov, and Peer Bork
Hum Mol Genet (2001) 10 591-597
http//genetics.bwh.harvard.edu/pph/ http//polydo
ms.cchmc.org/polydoms/
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Prediction Puzzles
gtexample1 CACCCTCGCCAGTTACGAGCTGCCGAGCCGCTTCCTAGGC
TCTCTGCGAATACGGACACG CATGCCACCCACAACAACTTTTTAAAAGA
ATCAGACGTGTGAAGGATTCTATTCGAATTA CTTCTGCTCTCTGCTTTT
ATCACTTCACTGTGGGTCTGGGCGCGGGCTTTCTGCCAGCTC CGCGGAC
GCTGCCTTCGTCCAGCCGCAGAGGCCCCGCGGTCAGGGTCCCGCGTGCGG
GGT ACCGGGGGCAGAACCAGCGCGTGACCGGGGTCCGCGGTGCCGCAAC
GCCCCGGGTCTGCG CAGAGGCCCCTGCAGTCCCTGCCCGGCCCAGTCCG
AGCTTCCCGGGCGGGCCCCCAGTCC GGCGATTTGCAGGAACTTTCCCCG
GCGCTCCCACGCGAAGC