Unbiased estimation of symmetrical directional mutation pressure from protein-coding DNA

The most generally applicable procedure for obtaining estimates of the symmetrical, or strandnonspecific, directional mutation pressure (microD) on protein-coding DNA sequences is to determine the G+C content at synonymous codon sites (Psyn), and to divide Psyn by twice the arithmetic mean of the G+C content at synonymous codon sites of a large number of randomly generated, synonymously coding DNA sequences (Psyn). Unfortunately, the original procedure yields biased estimates of Psyn and microD and is computationally expensive. We here present a fast procedure for estimating unbiased microD values. The procedure employs direct calculation of Psyn (approximately Psyn) and two normalization procedures, one for Psyn < or = Psyn and another for Psyn > or = Psyn. The normalization removes a bias sometimes caused by codons specifying arginine, asparagine, isoleucine, and leucine. Consequently, comparison of protein-coding genes that are translated using different genetic codes is facilitated.