The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure

Abstract

Abstract Background Activation induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) are deaminases that mutate C to U on single-stranded DNA (ssDNA). AID is expressed primarily in germinal center B-cells, where it facilitates affinity maturation and class-switch recombination. APOBEC3 are a family of anti-viral proteins that act as part of the intrinsic immune response. In both cases, there are particular sequence motifs, also known as “mutation motifs”, to which these deaminases prefer to bind and mutate. Results We present a program, the cytidine deaminase under-representation reporter (CDUR) designed to statistically determine whether a given sequence has an under/over-representation of these mutation motifs. CDUR shows consitency with other studies of mutation motifs, as we show by analyzing sequences from the adeno-associated virus 2 (AAV2) and human papillomavirus (HPV). Conclusion Using various shuffling mechanisms to generate different null model distributions, we can tailor CDUR to correct for metrics such as GC-content, dinucleotide frequency, and codon bias.

Keywords

• AID
• APOBEC
• Deaminase
• Mutation motifs
• Virus