title: Isochores exhibit evidence of genes interacting with the large-scale genomic environment.
abstract: The genomes of mammals and birds can be partitioned into megabase-long regions, termed isochores, with consistently high, or low, average C + G content. Isochores with high CG contain a mixture of CG-rich and AT-rich genes, while high-AT isochores contain predominantly AT-rich genes. The two gene populations in the high-CG isochores are functionally distinguishable by statistical analysis of their gene ontology categories. However, the aggregate of the two populations in CG isochores is not statistically distinct from AT-rich genes in AT isochores. Genes tend to be located at local extrema of composition within the isochores, indicating that the CG-enriching mechanism acted differently when near to genes. On the other hand, maximum-likelihood reconstruction of molecular phylogenetic trees shows that branch lengths (evolutionary distances) for third codon positions in CG-rich genes are not substantially larger than those for AT-rich genes. In the context of neutral mutation theory this argues against any strong positive selection. Disparate features of isochores might be explained by a model in which about half of all genes functionally require AT richness, while, in warm-blooded organisms, about half the genome (in large coherent blocks) acquired a strong bias for mutations to CG. Using mutations in CG-rich genes as convenient indicators, we show that approximately 20% of amino acids in proteins are broadly substitutable, without regard to chemical similarity.
authors.affiliation: Los Alamos National Laboratory, New Mexico 87545, USA. wpress@lanl.gov
authors.forename: William H
authors.initials: WH
authors.lastname: Press
authors.forename: Harlan
authors.initials: H
authors.lastname: Robins
mesh_terms: D000818:Animals; D018900:Dinucleotide Repeats / Q000235:genetics; D005828:Genetics, Population; D015894:Genome, Human / Q000502:physiology; D006801:Humans; D032085:Isochores / Q000235:genetics* / Q000502:physiology; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D015027:Zebrafish / Q000235:genetics
chemical_list: D032085:Isochores