Methods for estimating<unk>  and<unk>  use a sequence alignment of two or more nucleotide sequences of homologous genes that code for proteins (rather than being genetic switches, controlling development or the rate of activity of other genes). Methods can be classified into three groups: approximate methods, maximum-likelihood methods, and counting methods. However, unless the sequences to be compared are distantly related (in which case maximum-likelihood methods prevail), the class of method used makes a minimal impact on the results obtained; more important are the assumptions implicit in the chosen method. Approximate methods Approximate methods involve three basic steps: (1) counting the number of synonymous and nonsynonymous sites in the two sequences, or estimating this number by multiplying the sequence length by the proportion of each class of substitution; (2) counting the number of synonymous and nonsynonymous substitutions; and (3) correcting for multiple substitutions. These steps, particularly the latter, require simplistic assumptions to be made if they are to be achieved computationally; for reasons discussed later, it is impossible to exactly determine the number of multiple substitutions. Maximum-likelihood methods The maximum-likelihood approach uses probability theory to complete all three steps simultaneously. It estimates critical parameters, including the divergence between sequences and the transition/transversion ratio, by deducing the most likely values to produce the input data. Counting methods In order to quantify the number of substitutions, one may reconstruct the ancestral sequence and record the inferred changes at sites (straight counting – likely to provide an underestimate); fitting the substitution rates at sites into predetermined categories (Bayesian approach; poor for small data sets); and generating an individual substitution rate for each codon (computationally expensive). Given enough data, all three of these approaches will tend to the same result.
Ka/Ks ratio
E/A ratio
NC ratio
Rate pressure product
Extraction ratio
QT interval
QRS complex
PR interval