[Spatial association of nucleotide substitutions during the evolution of DNA sequences]

Evolutionary models for estimating the number of nucleotide substitutions between DNA sequences are evaluated with data from histone gene sequences of 7 remote species. It is found that the nucleotide compositions at the third codon position of H2A genes vary greatly among species and are highly correlated with the compositions at the first position of H2A genes, with those at the first and third position of H4 genes and with those in the up- and downstream sequences of H2A genes. This implies the existence of regional constraints over DNA sequences during the evolutionary process, which is different over species. Possible causes for the variations are increment of G + C content in higher eukarotypes, and chromosomal recombination, which brought the histone genes onto different isochores and thus under different selective or mutational pressures. Substitutions at different positions in a codon have been found not to be independent, probably due to multiple substitutions, i.e., single substitution events involving multiple sites. The implication of these results to phylogeny inferring is discussed.