Evolutionary preservation of CpG dinucleotides in RAG1 may elucidate the relatively high rate of methylation-mediated mutagenesis of RAG1 transposase.

ABSTRACT: Recombination-activating gene 1 (RAG1) is a vital player in V(D)J recombination, a fundamental process in primary B cell and T cell receptor diversification of the adaptive immune system. Current vertebrate RAG evolved from RAG transposon; however, it has been modified to play a crucial role in the adaptive system instead of being irreversibly silenced by CpG methylation. By interrogating a range of publicly available datasets, the current study investigated whether RAG1 has retained a disproportionate level of its original CpG dinucleotides compared to other genes, thereby rendering it more exposed to methylation-mediated mutation. Here, we show that 57.57% of RAG1 pathogenic mutations and 51.6% of RAG1 disease-causing mutations were associated with CpG methylation, a percentage that was

SUBMITTER: Fawzy MM 

PROVIDER: S-EPMC11217092 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature