Originally published as Genetics Published Articles Ahead of Print on August 20, 2008.

Genetics, Vol. 180, 639-647, September 2008, Copyright © 2008
doi:10.1534/genetics.108.090860

The Complementary Neighborhood Patterns and Methylation-to-Mutation Likelihood Structures of 15,110 Single-Nucleotide Polymorphisms in the Bovine Genome

Zhihua Jiang^*,1, Xiao-Lin Wu², Ming Zhang, Jennifer J. Michal and Raymond W. Wright, Jr.

Department of Animal Sciences, Washington State University, Pullman, Washington 99164-6351

¹ Corresponding author: Department of Animal Sciences, Washington State University, Pullman, WA 99164-6351.
E-mail: jiangz{at}wsu.edu

Bayesian analysis was performed to examine the single-nucleotide polymorphism (SNPs) neighborhood patterns in cattle using 15,110 SNPs, each with a flanking sequence of 500 bp. Our analysis confirmed three well-known features reported in plants and/or other animals: (1) the transition is the most abundant type of SNPs, accounting for 69.8% in cattle; (2) the transversion occurs most frequently (38.56%) in cattle when the A + T content equals two at their immediate adjacent sites; and (3) C T and A G transitions have reverse complementary neighborhood patterns and so do A C and G T transversions. Our study also revealed several novel SNP neighborhood patterns that have not been reported previously. First, cattle and humans share an overall SNP pattern, indicating a common mutation system in mammals. Second, unlike C T/A G and A C/G T, the true neighborhood patterns for A T and C G might remain mysterious because the sense and antisense sequences flanking these mutations are not actually recognizable. Third, among the reclassified four types of SNPs, the neighborhood ratio between A + T and G + C was quite different. The ratio was lowest for C G, but increased for C T/A G, further for A C/G T, and the most for A T. Fourth, when two immediate adjacent sites provide structures for CpG, it significantly increased transitions compared to the structures without the CpG. Finally, unequal occurrence between A G and C T in five paired neighboring structures indicates that the methylation-induced deamination reactions were responsible for 20% of total transitions. In addition, conversion can occur at both CpG sites and non-CpG sites. Our study provides new insights into understanding molecular mechanisms of mutations and genome evolution.

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