The ability to identify biological problems of significant intellectual value to both fields concern

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What Is Bioinformatics?
The ability to identify biological problems of
significant intellectual value to both fields
concerned.
Science 2911260 16 Feb 2001
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Bioinformatics genes, proteins and computers
Bio-Polymer (alphabet) Process
DNA (A,T,G,C) replication

transcription

mRNA (U,A,C,G) splicing
translation
Proteins (20 a.a.) folding

interactions
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Genetic Information
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DNA REPLICATION movie
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Transcription
RNA Polymerase
tRNA rRNA mRNA
Gene
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E. coli has single chromosome gt 2000
Promoter Sites
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Procaryotic promoters
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RNA Polymerase
Binds to Promoter Site (s subunit dissociates)
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... unwinds DNA helix
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... unwinds DNA helix
.... and forms new RNA strand in 5? - 3?
direction .... rejoining DNA helix
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TRANSCRIPTION movie.....
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Multiple Copies made Simultaneously
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Termination Sequence
AGCCGCCAGTTCCGCTGGCGGCAT TT T TCGGCGGTCAAGGCGACCGC
CGTAAAA
AGCCGCCAGUUCCGCUGGCGGCAUUUU
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RNA Products
RNA size function wt
tRNA small bind aa 80
41 read
codon rRNA large ribosome 15
3 mRNA medium genetic code 5
1000s
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Ribonucleases RNAase
Exonucleases from 3 end only
Endonucleases middle cuts
may include splicing
RNAase Function digest unnecessary RNA
Process Primary transcripts at
specific cleavage sites
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E. coli rRNA gene
16s 23s 5s
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16s 23s
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3
-CCA-3
5
--- Add --- Cut/splice
tRNAs have sections removed
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Uninterrupted Genes
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Prokaryotic gene model ORF-genes

• Small genomes, high gene density
• Haemophilus influenza genome 85 genic
• Operons
• One transcript, many genes
• No introns.
• One gene, one protein
• Open reading frames
• One ORF per gene
• ORFs begin with start,
• end with stop codon (def.)

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Interrupted Genes
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EUKARYOTIC MODELS
EXON In protein coding genes,.the segment of a
eukaryotic gene that consists of a sequence of
nucleotides that will be messenger RNA and than
protein.
INTRON Non coding region of eukaryotic gene
(transcribed into RNA than spliced)
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Annotation of eukaryotic genomes
Genomic DNA
transcription
Unprocessed RNA
RNA processing
Mature mRNA
AAAAAAA
Gm3
translation
Nascent polypeptide
folding
Active enzyme
Reactant A
Product B
Function
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Eukaryotic gene model spliced genes

• Posttranscriptional modification
• 5-CAP, polyA tail, splicing
• Open reading frames
• Mature mRNA contains ORF
• All internal exons contain open read-through
• Multiple translates
• One gene many proteins via alternative splicing

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primary transcript
splicosome
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vs.
dsDNA intron
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Exon-Intron Borders Splice Sites
Exon Intron
Exon  gaggcatcagGTttgtagactgtgtttcAG
tgcacccact ccgccgctgaGTgagccgtgtc
tattctAGgacgcgcggg tgtgaattagGTaagaggtt
atatctccAGatggagatca ccatgaggagGTgagtg
ccattatttccAGgtatgagacg
Splice site Splice site
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Modular Theory of Protein Evolution
Exons were once entire genes 20 aa is smallest
folding unit smallest exons 20aa
Gene duplication Genetic Crossover
Transposition moves gene location gene becomes
exon in larger gene at new location
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Modular Theory of Protein Evolution
Introns can be deleted to produce larger exons.
Many proteins can share exons which originated
from same gene but the whole protein has
distinct function.
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Same gene alternate splicing
Antigen recognition cell
Antibody producing cell
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Exon Examples
Legehemoglobin has 4 exons exons 2 3
correspond to exon 2 in mammalian Hemoglobin
rodents have 2 insulin genes 2nd has one
less exon
mammallian systems can splice yeast RNA
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Addition Eucaryotic mRNA Processing
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TRANSLATION movie.....
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