Skew of Mononucleotide Frequencies, Relative Abundance of Dinucleotides, and DNA Strand Asymmetry

Abstract

Based on 152 mitochondrial genomes and 36 bacterial chromosomes that have been completely se- quenced, as well as three long contigs for human chro- mosomes 6, 21, and 22, we examined skews of mono- nucleotide frequencies and the relative abundance of dinucleotides in one DNA strand. Each group of these genomes has its own characteristics. Regarding mito- chondrial genomes, both C p G and G p T are underrepre- sented, while either G p Go r C p C or both are overrepre- sented. The relative frequency of nucleotide T vs A and of nucleotide G vs C is strongly skewed, due presumably to strand asymmetry in replication errors and unidirec- tional DNA replication from single origins. Exceptions are found in the plant and yeast mitochondrial genomes, each of which may replicate from multiple origins. Re- garding bacterial genomes, the universal rule of C pG deficiency is restricted to archaebacteria and some eu- bacteria. In other eubacteria, the most underrepresented dinucleotide is either Tp Ao r G pT. In general, there are significant T vs A and G vs C skews in each half of the bacterial genome, although these are almost exactly can- celed out over the whole genome. Regarding human chromosomes 6, 21, and 22, dinucleotide CpG tends to be avoided. The relative frequency of mononucleotides ex- hibits conspicuous local skews, suggesting that each of these chromosomal segments contains more than one DNA replication origin. It is concluded that, when there are several replicons in a genomic region, not only the number of DNA replication origins but also the direc- tionality is important and that the observed patterns of nucleotide frequencies in the genome strongly support the hypothesis of strand asymmetry in replication errors.