THE EFFECT OF EVENLY SPACED CONSTANT SITES ON THE DISTRIBUTION OF THERANDOM DIVISION OF A MOLECULAR SEQUENCE

Motivation: A modified Sherman statistic can be used to test whether t he differences between two aligned sequences are distributed at random along the sequences, or whether they are cluster ed, which suggests a nomalies of evolution such as pm tial gene I recombination or function al constraints. The presence of evenly spaced constant sires (such as constancy at the second codon position in genes coding for proteins) l owers the statistic and makes the significance less than it should be. Results: The magnitude of the constant-site effect is shown by simula tion to depend mainly on the proportion of differences between two seq uences and on the number of constant sites that are added after each v ariable site. This latter number can be estimated from the variance of sites in a sequence matrix at the first, second and third codon posit ions, to obtain a ratio that corrects the statistic. When expressed as standard errors, the uncorrected results ar-e too low (typically half to one unit when almost all the variation is at the third codon posit ion). Correction raises the standard errors to levels close to expecta tion. If the data Show no mal ked ternary periodicity the correction i s very small. The method is illustrated with biological data that show close to random behaviour; and with data that exhibit strong clusteri ng. Availability: The software is available from the author and has al so been placed on the EMBL file server (Software @embl-ebi.ac.uk). Con tact: phas1@le.ac.uk.