Evidence of bias towards buffered codons in human transcripts.

Codon usage bias is well established in different species from bacteria to mammals. A number of models have been proposed to show this bias as a balance between mutation and selection. Most of these models emphasize controlling the speed of protein translation from the mRNA and increasing the accuracy where this bias is dependent on the abundance and properties of the available tRNA. In this work, codon usage bias in general is considered from a different angle based on a new hypothesis where selection is expected to act in a direction to favor codons that are more buffered, or protected, from mutation than those more sensitive to mutation. It is anticipated that the more buffered the original coding sequence, the higher the survival chance for the whole organism since the resulting protein sequence remains unchanged. Two different complementary measures are developed to compute the average buffering capacity in a given sequence. We show that the buffering capacity of coding sequences in humans is in general higher than that of randomly generated sequences and that of shifted reading frames. Highly expressed genes are shown to have an even higher buffering capacity than non-housekeeping genes. This result is to be expected due to the necessity of housekeeping genes.