Codon Bias and its Codon Bias and its Relationship to Gene Relationship to Gene ExpressionExpression

Presented through a virtual Presented through a virtual grant by the Virtual Student grant by the Virtual Student Union.Union.

What is Codon Bias?What is Codon Bias?

Codon bias is the probability that a Codon bias is the probability that a given codon will be used to code given codon will be used to code for an amino acid over a different for an amino acid over a different codon which codes for the same codon which codes for the same amino acid.amino acid.

How May Codon Bias How May Codon Bias Relate to Gene Relate to Gene Expression? Expression?

Genes that are always expressed at a Genes that are always expressed at a high rate should have a different codon high rate should have a different codon bias than those genes that are always bias than those genes that are always expressed at a low rate.expressed at a low rate.

Genes whose expression varies from Genes whose expression varies from low expression to high expression as a low expression to high expression as a given environmental condition changes given environmental condition changes may have a codon bias similar to the may have a codon bias similar to the highly expressed genes.highly expressed genes.

How May Codon Bias How May Codon Bias Relate to Gene Relate to Gene Expression? (cont’d)Expression? (cont’d)

If a gene is expressed at a low If a gene is expressed at a low level for all known conditions, but level for all known conditions, but shares a codon bias similarity with shares a codon bias similarity with the highly or variably expressed the highly or variably expressed genes, it is possible that the gene genes, it is possible that the gene is expressed at a high rate under is expressed at a high rate under some as yet unknown some as yet unknown environmental condition.environmental condition.

How Does One Verify This How Does One Verify This Hypothesis?Hypothesis?

Must use a genome in which the Must use a genome in which the sequence of every ORF is known.sequence of every ORF is known.

Must use a genome in which the Must use a genome in which the transcriptional rate is known for transcriptional rate is known for every ORF as a standard condition every ORF as a standard condition varies.varies.

Specifically, How was this Specifically, How was this Done?Done?

Specifically, the Specifically, the S. cerevisiaeS. cerevisiae geneome was geneome was used, because every ORF is sequenced.used, because every ORF is sequenced.

The Yeast Expression Database contains The Yeast Expression Database contains the rate of transcription for each ORF in the the rate of transcription for each ORF in the S. cerevisiaeS. cerevisiae genome. genome.

The Yeast Expression Database also The Yeast Expression Database also measures the change in transcription rate measures the change in transcription rate as the yeast move from a high glucose to as the yeast move from a high glucose to low glucose concentration.low glucose concentration.

What was Done with the What was Done with the Data?Data?

First, the every ORF in the Metabolic First, the every ORF in the Metabolic Database was ranked from highest to lowest Database was ranked from highest to lowest expressed genes.expressed genes.

Next, the ORFs in the Database were ranked Next, the ORFs in the Database were ranked using the genes that had the greatest using the genes that had the greatest difference in expression between high and difference in expression between high and low glucose concentration.low glucose concentration.

The codon frequencies from the 5 highest, 5 The codon frequencies from the 5 highest, 5 lowest and 3 most varied sequences were lowest and 3 most varied sequences were then analyzed further.then analyzed further.

Codon Frequency ResultsCodon Frequency Results

Glu and Val codon expression is similar Glu and Val codon expression is similar in high and variably expressed genes.in high and variably expressed genes.

Glu and Val codon expression appears Glu and Val codon expression appears different in the typical low expressed different in the typical low expressed gene.gene.

Chi squared analysis suggests that Chi squared analysis suggests that these variances are due to more than these variances are due to more than random probability.random probability.

Increase the Increase the sample size to sample size to include the entire include the entire genomegenome

What are Our Future What are Our Future Goals?Goals?

Look for genes Look for genes with low with low expression whose expression whose codon bias more codon bias more closely resembles closely resembles the highly the highly expressed or expressed or variably variably expressed genes.expressed genes.

Future goals (cont’d)Future goals (cont’d)

A scoring system A scoring system must be created must be created to classify gene to classify gene expression.expression.

Must search Must search genome using genome using many different many different environmental environmental condtions.condtions.

The technique The technique can be applied to can be applied to other genomes.other genomes.