Analyses of the genomes of three prokaryotes, Escherichia coli, Bacillus subtilis, and Haemophilus influenzae, revealed a new type of genomic compartmentalization of base frequencies. There was a departure from intrastrand equifrequency between A and T or between C and G, showing that the substitution patterns of the two strands of DNA were asymmetric. The positions of the boundaries between these compartments were found to coincide with the origin and terminus of chromosome replication, and there were more A-T and C-G deviations in intergenic regions and third codon positions, suggesting that a mutational bias was responsible for this asymmetry. The strand asymmetry was found to be due to a difference in base compositions of transcripts in the leading and lagging strands. This difference is sufficient to affect codon usage, but it is small compared to the effects of gene expressivity and amino-acid composition.
G:C pairs are more stable than A:T pairs because they have an additional hydrogen bond. This has led to many studies on the correlation between the guanine+cytosine (G+C) content of nucleic acids and temperature over the last 20 years. We collected the optimal growth temperatures (Topt) and the G+C contents of genomic DNA; 23S, 16S, and 5S ribosomal RNAs; and transfer RNAs for 764 prokaryotic species. No correlation was found between genomic G+C content and Topt, but there were striking correlations between the G+C content of ribosomal and transfer RNA stems and Topt. Two explanations have been proposed-neutral evolution and selection pressure-for the approximate equalities of G and C (respectively, A and T) contents within each strand of DNA molecules. Our results do not support the notion that selection pressure induces complementary oligonucleotides in close proximity and therefore numerous secondary structures in prokaryotic DNA, as the genomic G+C content does not behave in the same way as that of folded RNA with respect to optimal growth temperature.
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