The Cytidine Deaminase Under-representation Reporter (CDUR) As a Tool to Study Evolution of Sequences Under Deaminase Mutational Pressure

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2018 May 3

PMID 29716522

Citations 10

Authors

Maxwell Shapiro

Stephen Meier

Thomas MacCarthy

Affiliations

Soon will be listed here.

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.

Citing Articles

Evolvability of cancer-associated genes under APOBEC3A/B selection.

Song J, Davalos L, MacCarthy T, Damaghi M iScience. 2024; 27(4):109433.

PMID: 38550998 PMC: 10972820. DOI: 10.1016/j.isci.2024.109433.

Evolvability of cancer-associated genes under APOBEC3A/B selection.

Song J, Davalos L, MacCarthy T, Damaghi M bioRxiv. 2023; .

PMID: 38106028 PMC: 10723265. DOI: 10.1101/2023.08.27.554991.

Human cytomegalovirus mediates APOBEC3B relocalization early during infection through a ribonucleotide reductase-independent mechanism.

Fanunza E, Cheng A, Auerbach A, Stefanovska B, Moraes S, Lokensgard J J Virol. 2023; 97(8):e0078123.

PMID: 37565748 PMC: 10506462. DOI: 10.1128/jvi.00781-23.

Human cytomegalovirus mediates APOBEC3B relocalization early during infection through a ribonucleotide reductase-independent mechanism.

Fanunza E, Cheng A, Auerbach A, Stefanovska B, Moraes S, Lokensgard J bioRxiv. 2023; .

PMID: 36778493 PMC: 9915650. DOI: 10.1101/2023.01.30.526383.

Mutational pressure by host APOBEC3s more strongly affects genes expressed early in the lytic phase of herpes simplex virus-1 (HSV-1) and human polyomavirus (HPyV) infection.

Shapiro M, Krug L, MacCarthy T PLoS Pathog. 2021; 17(4):e1009560.

PMID: 33930088 PMC: 8115780. DOI: 10.1371/journal.ppat.1009560.

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