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Updated: Jun 11, 2026
04:52
Following the Dynamics of Structural Variants in Experimentally Evolved Populations
Published on: February 3, 2023
A time-invariant principle of genome evolution
1Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom. sde@mrc-lmb.cam.ac.uk
Summary
Structural alterations, like insertions and deletions, directly increase single-nucleotide changes nearby. This link between mutation types holds true across different species, personal genomes, and cancer cells, impacting genome evolution and disease genomics.
Area of Science:
- Genomics and Evolutionary Biology
- Molecular Genetics
- Cancer Genomics
Background:
- Understanding genome evolution requires identifying time-invariant principles applicable to both germ and somatic cells.
- The interplay between structural alterations (insertions/deletions) and single-nucleotide substitutions is crucial for genomic studies.
- Implications span genome-wide association studies (GWAS), gene therapy, and disease genomics.
Purpose of the Study:
- To investigate the relationship between structural alterations and single-nucleotide substitutions across diverse evolutionary timescales and cell lineages.
- To determine if structural changes induce nearby single-nucleotide mutations.
- To explore the molecular mechanisms underlying this observed mutational linkage.
Main Methods:
- Comparative genomics of human and chimpanzee genomes (millions of years).
- Analysis of human personal genomes (tens of thousands of years).
- Examination of structurally altered regions in cancer and genetically engineered cells (days).
Main Results:
- Genes near structural alterations exhibit increased single-nucleotide changes and faster evolution at the species level.
- In personal genomes, single-nucleotide substitution rates are elevated near structural alterations, decreasing with distance.
- Single-nucleotide changes frequently occur near structural alterations in cancer and engineered cells.
Conclusions:
- Structural alterations demonstrably induce single-nucleotide changes in adjacent genomic regions.
- The low fidelity of error-prone repair polymerases during break-repair is a proposed mechanism for these mutations.
- Structural alterations and single-nucleotide changes are interconnected mutational events across various timescales and cell types, necessitating a unified analytical framework.
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