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Evolution of sequences mostly involves independent changes at different sites. However, substitutions at neighboring sites may co-occur as multinucleotide replacement events (MNRs). Here, we compare noncoding sequences of several species of primates, and of three species of Drosophila fruit flies, in a phylogenetic analysis of the replacements that occurred between species at nearby nucleotide sites. Both in primates and in Drosophila, the frequency of single-nucleotide replacements is substantially elevated within 10 nucleotides from other replacements that occurred on the same lineage but not on another lineage. The data imply that dinucleotide replacements (DNRs) affecting sites at distances of up to 10 nucleotides from each other are responsible for 2.3% of single-nucleotide replacements in primate genomes and for 5.6% in Drosophila genomes. Among these DNRs, 26% and 69%, respectively, are in fact parts of replacements of three or more trinucleotide replacements (TNRs). The plurality of MNRs affect nearby nucleotides, so that at least six times as many DNRs affect two adjacent nucleotide sites than sites 10 nucleotides apart. Still, approximately 60% of DNRs, and approximately 90% of TNRs, span distances more than two (or three) nucleotides. MNRs make a major contribution to the observed clustering of substitutions: In the human–chimpanzee comparison, DNRs are responsible for 50% of cases when two nearby replacements are observed on the human lineage, and TNRs are responsible for 83% of cases when three replacements at three immediately adjacent sites are observed on the human lineage. The prevalence of MNRs matches that is observed in data on de novo mutations and is also observed in the regions with the lowest sequence conservation, suggesting that MNRs mainly have mutational origin; however, epistatic selection and/or gene conversion may also play a role. [ABSTRACT FROM PUBLISHER]

Mutation rate varies between sites in the genome. Part of this variation can be explained by well-recognized short nucleotide contexts, but a large component of this variation remains cryptic. We used data on interspecies divergence and intraspecies polymorphism in Drosophila and Hominidae to analyze variation of the average rate of the 12 possible kinds of single-nucleotide mutations and in the transition/transversion ratio κ at single-nucleotide resolution. Both the average mutation rate and κ vary by a factor of ∼3 between nucleotide sites. The characteristic scale of variation in κ is up to at least ∼30 nucleotides in Drosophila and ∼5 nucleotides in Hominidae. Genome segments with locally elevated mutation rates possess lower values of κ; however, a substantial fraction of variation in κ cannot be directly explained by the local mutation rates. [ABSTRACT FROM PUBLISHER]

Abstract: Genomes are characterized by global and local compositional properties that are interesting in an evolutionary perspective but also provide useful information for the identification of some functional elements. Following previous studies, in this work we investigated compositional properties of non-coding sequences in four eukaryotic genomes (C. elegans, D. melanogaster, M. musculus, H. sapiens). We developed a procedure based on Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) to identify pentamers that are over-represented in introns (intron vocabulary) and to define a new parameter (LD) that reflects oligonucleotide composition of a given sequence. We analyzed genomic sequences and we found that all non-coding parts of a genome are characterized by similar LD values. Furthermore, we used the new parameter to analyze potentially regulatory regions. We extracted non-redundant sets of promoter sequences for D. melanogaster and H. sapiens and we studied their compositional (G+C content and LD parameter) and conformational (bendability propensity) properties. We found that regions immediately surrounding transcription start sites are distinguishable because of their %G+C, LD and bendability values. [Copyright &y& Elsevier]