Isochore evolution in mammals: A human-like ancestral structure

Codon usage in mammals is mainly determined by the spatial arrangement of g enomic G + C-content, i.e., the isochore structure. Ancestral G + C-content at third codon positions of 27 nuclear protein-coding genes of eutherian m ammals was estimated by maximum-likelihood analysis on the basis of a nonho mogeneous DNA substitution model, accounting for variable base compositions among present-day sequences. Data consistently supported a human-like ance stral pattern, i.e., highly variable G + C-content among genes. The mouse g enomic structure-more narrow G + C-content distribution-would be a derived state. The circumstances of isochore evolution are discussed with respect t o this result. A possible relationship between G + C-content homogenization in murid genomes and high mutation rate is proposed, consistent with the n egative selection hypothesis for isochore maintenance in mammals.