gene and protein

8/8/2019 Gene and Protein

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Gene, Proteins, and Genetic Code


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Protein Synthesis in a Cell


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Protein and Amino Acids


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Protein


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Protein

GOT Ecoli


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A protein sequence>gi|7228451|dbj|BAA92411.1| EST AU055734(S20025) corresponds to a region

MCSYIRYDTPKLFTHVTKTPPKNQVSNSINDVGSRRATDRSVASCSSEKSVGTMSVKNASSISFEDIEKSISNWKIPKVN

IKEIYHVDTDIHKVLTLNLQTSGYELELGSENISVTYRVYYKAMTTLAPCAKHYTPKGLTTLLQTNPNNRCTTPKTLKWD

EITLPEKWVLSQAVEPKSMDQSEVESLIETPDGDVEITFASKQKAFLQSRPSVSLDSRPRTKPQNVVYATYEDNSDEPSI

SDFDINVIELDVGFVIAIEEDEFEIDKDLLKKELRLQKNRPKMKRYFERVDEPFRLKIRELWHKEMREQRKNIFFFDWYE

SSQVRHFEEFFKGKNMMKKEQKSEAEDLTVIKKVSTEWETTSGNKSSSSQSVSPMFVPTIDPNIKLGKQKAFGPAISEEL

VSELALKLNNLKVNKNINEISDNEKYDMVNKIFKPSTLTSTTRNYYPRPTYADLQFEEMPQIQNMTYYNGKEIVEWNLDG

FTEYQIFTLCHQMIMYANACIANGNKEREAANMIVIGFSGQLKGWWNNYLNETQRQEILCAVKRDDQGRPLPDRDGNGNP

TELKEGFHMEEKDEPIQEDDQVVGTIQKYTKQKWYAEVMYRFIDGSYFQHITLIDSGADVNCIREDEILDQLVQTKREQV

VNSIYLHDNSFPKSMDLPDQKITEKRAKLQDIPHHEERLLDYREKKSRDGQDKLPMEVEQSMATNKNTKILLRAWLLST

A protein sequence may have a few hundreds to several

thousands amino acids.


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Protein synthesis


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Genetic code.

.

AT

T

C

A

CA

G

T

GG

A

.

.

I

H

S

G


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Notes on translation

Three Reading frames

Third base not important

5 -> 3

Start and end codon

Open Reading Frame (ORF)

Each gene is an ORF, but not all ORF aregenes.


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The Central Dogma of Molecular Biology

DNA RNA Proteintranscript translation

replication

genotype phenotype


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Exception retroviruses

DNA RNA Proteintranscript translation

replication

genotype phenotype


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ProteinPhenotype

DNA

(Genotype)

Biology


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Genes One gene encodes one protein (or sometimesRNA).

Like a program, it starts with start codon (e.g.

ATG), then each three code one amino acid. Thena stop codon (e.g. TGA) signifies end of the gene.

Genes are dense in prokaryotes and sparse ineukaryotes.

In the middle of a eukaryotic gene, there areintrons that are spliced out (as junk) aftertranscription. Good parts are called exons. This isthe task of gene finding.


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Gene related diseases Hemophilia: on X chromosome.

Sickle-Cell Anemia: single nucleotide mutation in the firstexon of beta-globin gene (removes a cutting site). 1 in 12African Americans are carriers. (sick for homozygotes)

BRCA1 gene (chr. 17q) responsible for inheritedbreast cancer (10% of breast cancer)

Fragile X syndrome (mentally retard) 1 in 1250 males,

2500 females (dominate, but females have partiallyexpressed good gene). FMR-1 gene: tri-nucleotide repeats>200 causes disease.

P53 gene: chr. 17p, tumor suppressor protein.


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Genetic Test Example:

http://www.myriad.com/index.php

Cons and Pros: Can possibly avoid/early diagnose the disease.

Can make you unhappier

Can help insurance company discriminate thedefected gene carriers


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Gene Prediction and Annotation

Prokaryotes

1. Start/stop codon (ORF)

2. Promoters

3. Content4. Sequence similarity


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Start Codon

May miss short genes.

Do not know which start codon to use.

Overlapping ORF at different reading frames.


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Promoters

5'-XXXXPPPPPPXXXXXXXXXPPPPPPXXXXGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGG XXXX-3

-35 -10 Gene to be transcribed

-10: T A T A A T

77% 76% 60% 61% 56% 82%

-35: T T G A C A

69% 79% 61% 56% 54% 54%

Pribnow box

Inprokaryotes, the promoter consists of two short sequences at -10 and -35 position

upstream of the gene, that is, prior to the gene in the direction of transcription. The

sequence at -10 is called the Pribnow box and usually consists of the six nucleotides

TATAAT. The Pribnow box is absolutely essential to start transcription in prokaryotes. The

other sequence at -35 usually consists of the six nucleotides TTGACA. Its presence allows

a very high transcription rate.

These rules are only

approximately correct.


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Scoring a 6-mer as Pribnow box Computers deal with exact formulae but not

English description.

We need a score function to measure thelikelihood that a 6-mer is a pribnow box


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An exemplary function for pribnow

box fitness evaluation

log()


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Content I codon bias A codon XYZ occurs with different freqencies in

coding regions and non-coding regions

different amino acids have different freq.

Diff. codons for the same amino acid have diff. freq. In non-coding regions approx. p(X)*p(Y)*p(Z)


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http://www.kazusa.or.jp/codon/


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Content II - Hidden Markov

Model (HMM)


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Eukaryotes Basic idea similar to Prokaryotes

Difference:


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DN

A-specific transcription factors

These are the basic of gene-regulatorynetwork

Another hot area in Bioinformatics


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Splicing

Consensus sequences have been identified as necessary butnot sufficient forsplicing. In vertebrates, these sequencesare (the slash identifies the exon-intron or intron-exon

junction): C(orA)AG/GTA(orG)AGT "donor" splice site

T(orC)nNC(orT)AG/G "acceptor" splice site.

A third sequence, which in yeast is TACTAAC , is necessarywithin the intron sequence.

These rules are only

approximately correct.


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Gene Prediction Software Try Gene Scan at

http://genes.mit.edu/GENSCAN.htmlby

using the sequence at

http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=3253144

Did Gene Scan work well?

gene and protein

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