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DNA mismatch repair protein Mlh1 (MutL protein homolog 1) [COCA2]


The somatic mutation landscape of the human body.

Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized. To gain a better understanding of the genome-wide distribution and functional impact of somatic mutations, we leverage the genomic information contained in the transcriptome to uniformly call somatic mutations from over 7500 tissue samples, representing 36 distinct tissues. This catalog, containing over 280,000 mutations, reveals a wide diversity of tissue-specific mutation profiles associated with gene expression levels and chromatin states. For example, lung samples with low expression of the mismatch-repair gene MLH1 show a mutation signature of deficient mismatch repair. In addition, we find pervasive negative selection acting on missense and nonsense mutations, except for mutations previously observed in cancer samples, which are under positive selection and are highly enriched in many healthy tissues. These findings reveal fundamental patterns of tissue-specific somatic evolution and shed light on aging and the earliest stages of tumorigenesis.

MeSH Terms

  • Age Factors
  • Aging
  • Humans
  • Mutation
  • Neoplasms
  • Selection, Genetic
  • Sex Factors


  • Aging
  • Cancer
  • Genomic instability
  • Human
  • Somatic evolution
  • Somatic mutation

RNA-Seq analysis of differentially expressed genes relevant to mismatch repair in aging hematopoietic stem-progenitor cells.

We used RNA-sequencing (RNA-Seq) technology and an old hematopoietic stem and progenitor cells (HSPCs) model in vitro to analyze differential expressions of mismatch repair (MMR)-related genes in aged HSPCs, so as to explore the mechanism of DNA MMR injury in hematopoietic stem cells (HSC) aging. In this study, by combining RNA-seq data and National Center for Biotechnology Information database, we focus on six widely reported MMR genes MSH2, MSH3, MSH6, MLH1, PMS1, PMS2, and five MMR genes with closer ties to HSC aging Pcna, Exo1, Rpa1, Rpa2, and Rpa3 according to the genes functional classification and the related signaling pathway. It is concluded that MMR is closely related to HSC aging. This study provides experimental evidence for future researching MMR in HSC aging.


  • RNA-Seq
  • aging
  • hematopoietic stem and progenitor cells
  • mismatch repair