Genetics Problem Spaces

Introduction Problem Spaces Codon Usage Overview Intro Exercise Research Questions Literature Resources Assignments Student Projects

Codon Usage Overview An important feature of the genetic code is its degenerate structure. Degeneracy refers to the observation that more than one codon can specify the same amino acid. Of the twenty amino acids, eighteen are specified by two or more codons. For example, the codons CGU, CGC, CGA, CGG all specify the amino acid arginine. Whenever any one of these four codons is in the mRNA, the translational machinery will insert a arginine at that position in the polypeptide chain. In this sense, these four codons are functionally equivalent. The same would hold true for the other 18 amino acids that are specified by more than one codon. Although different codons may specify the same amino acid, they are not usually used with equal frequency. For example when arginine is specified in the 5028 open reading frames of Escherichia coli, CGU and CGC are four times more likely to be used than CGA or CGG. So even though all four codons specifiy arginine, some are much more likely to be used than others. This phenomena of unequal use of codons specifying the same amino acid is called codon bias. The biological significance of codon bias is not fully understood. The uneven use of codons is too severe to be reasonable accounted for by chance deviation. Additionally, different taxa show different patterns of bias. For example, while Escherichia coli uses CGG to specify arginine only 10% of the time, in Homo sapiens CGG specifies arginine 34% of the time. While most researchers suggest that codon bias is a result of natural selection, there is disagreement about the nature of the selective agent. Some researchers have proposed that codon bias is an adaptation to slight differences found in the translational machinery of different species. For example, the cells of some species might not contain equal concentrations of the cognate tRNA for a particular amino acid. Consider the amino acid arginine which is specified by several different codons. All organisms have several cognate tRNA for arginine with differing anticodons. It is possible that these different tRNA’s are not equally abundant in cells. For example, in Escherichia coli there may be more tRNA’s with anticodons complementary to CGU and CGC than tRNA’s with anticodons complementary to CGG and CGA. Therefore, there may be selection for alleles that use the CGU and CGC codons versus the CGG and CGA codons. After thousands of generations of selection this will result in codon bias in a genome. Other researchers have proposed that codon bias might not be due to differences in translational machinery. Instead codon bias may be due to other factors in nucleic acid metabolism. For example codon bias may due to selection for mRNA sequences that affect the stability of the mRNA.