Functional landscape of genome-wide postzygotic somatic mutations between monozygotic twins.

Monozygotic (MZ) twins originate from a single fertilized egg, making them genetically identical at the time of conception. However, postzygotic somatic mutations (PZMs) can introduce genetic differences after separation. Although whole-genome sequencing (WGS) sheds light on somatic mutations in cancer genomics, its application in genomic studies of MZ twins remains limited. In this study, we investigate PZMs in 30 healthy MZ twin pairs from the Osaka University Center for Twin Research using WGS (average depth = 23.8) and a robust germline-calling algorithm. We find high genotype concordance rates (exceeding 99%) in MZ twins. We observe an enrichment of PZMs with variant allele frequency around 0.5 in twins with highly concordant genotypes. These PZMs accumulate more frequently in non-coding regions compared with protein-coding regions, which could potentially influence gene expression. No significant association is observed between the number of PZMs and age or sex. Direct sequencing confirms a missense mutation in the ANKRD35 gene among the PZMs. By applying a genome-wide mutational signature pattern technique, we detect an age-related clock-like signature in these early postzygotic somatic mutations in MZ twins. Our study provides insights that contribute to a deeper understanding of genetic variation in MZ twins.