title: The apparent enhancement of CpG transversions in primate lineage is a consequence of multiple replacements.
abstract: We claim that the apparently enhanced CpG transversions in the form CpG to CpC/GpG or to ApG/CpT are caused by the hypermutable CpG to CpA/TpG transition. The nucleotide replacement counts obtained from the human/chimpanzee/gorilla/orangutan sequence alignments representing the replacements due to the evolutionary species divergence and the results of 1000 genomes project that provide us with the differences due to the intraspecies diversification were analyzed to estimate the ratio of CpG versus non-CpG transversion probabilities. The trinucleotide replacement counts were extracted from the regions that are free of functional constraints. The CpG transversion probabilities based upon the genomic comparisons were found to exceed more than twice the non-CpG transversions. The diversity data emerging from 14 population groups were partitioned in five classes as a function of the parameter quantifying the spread of the polymorphic allele among the group of individuals. The results based upon the human polymorphism exhibit a trend where CpG over non-CpG transversion probability ratio is less and less exceeding unity as the values of the derived allele frequency (DAF) of snps are diminishing. A computer simulation of a simplified model indicates that the phenomenon of the apparent enhancement of CpG transversions can have its source in the interference of the entropic effects with the maximum likelihood methodologies.
authors: National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors: Branko
authors: B
authors: Borštnik
authors: Danilo
authors: D
authors: Pumpernik
mesh_terms: D000818:Animals; D019295:Computational Biology; D003198:Computer Simulation; D018899:CpG Islands; D019143:Evolution, Molecular; D049810:Genetic Speciation; D014644:Genetic Variation; D006071:Gorilla gorilla / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009010:Monte Carlo Method; D002679:Pan troglodytes / Q000235:genetics; D011110:Polymorphism, Genetic; D057079:Pongo / Q000235:genetics; D011323:Primates / Q000235:genetics*; D013045:Species Specificity
keywords: CpG hypermutability; Transitions; homo sapiens; transversions