The complementary neighborhood patterns and methylation-to-mutation likelihood structures of 15,110 single-nucleotide polymorphisms in the bovine genome

Abstract

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 approximately 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.

Figure 1.—

The same overall neighborhood patterns flanking all SNPs in cattle (left) and human (right).

Figure 2.—

The neighborhood patterns of nucleotide distributions flanking the C ↔ T (A), A ↔ G (B), G ↔ T (C), A ↔ C (D), A ↔ T (E), and C ↔ G (F) substitutions. Solid lines represent medians of nucleotide frequencies, and top and bottom dotted lines are the corresponding 2.5- and 97.5-quantiles.

Figure 3.—

Effects of adjacent neighborhood structures on transitional SNP frequencies.