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2L, where L is the total number of aligned nucleotides (sample size), ObsS and ObsD are the numbers of changes observed as single- and double-nucleotide substitutions, respectively, RealS and RealD are the numbers of changes that have occurred as single- and simultaneous double-nucleotide substitutions, respectively, and ExpD is the number of doublet substitutions (observed at adjacent nucleotides) that have occurred by coincidence of two separate single-nucleotide changes. The difference of ObsD and ExpD was evaluated by a chi-squared test. In mammalian genomes, CG dinucleotides are methylated, which renders them susceptible to mutation (by deamination), yielding TC and CA dinucleotides at relatively high frequencies [A. P. Bird, Nucleic Acids Res. 8, 1499 (1980)]. To prevent sequential CN→CG→TG and NG→CG→CA changes (or parallel CC→TG and CG→CA mutations in independent lineages) from being counted as doublet mutations, CN→TG and NG→CA substitutions were excluded from the analysis. We also examined the rates of substitution of each of the four nucleotides separately; the biases in these rates are not sufficient to affect our results.
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This work was initiated in the Genetics Department of Trinity College, University of Dublin, and was continued with the support of C. Delidakis at the IMBB, Crete. It was supported in part by the EPET II programme of the General Secretariat for Research and Technology, Greece, and a UK Biotechnology and Biological Sciences Research Council grant G04905
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This work was initiated in the Genetics Department of Trinity College, University of Dublin, and was continued with the support of C. Delidakis at the IMBB, Crete. It was supported in part by the EPET II programme of the General Secretariat for Research and Technology, Greece, and a UK Biotechnology and Biological Sciences Research Council grant G04905.
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