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The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
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Related Experiment Video

Updated: Jul 8, 2025

Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
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Time-resolved, integrated analysis of clonally evolving genomes.

Carine Legrand1,2, Ranja Andriantsoa1, Peter Lichter3,4

  • 1Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.

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|December 14, 2023
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Summary

This study introduces a new framework to analyze clonal genome evolution, estimating key parameters like mutation rates and time. It successfully predicted the marbled crayfish speciation date and revealed insights into glioblastoma tumor progression.

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Area of Science:

  • Evolutionary Biology
  • Genomics
  • Cancer Research

Background:

  • Clonal genome evolution is fundamental to asexual reproduction and cancer.
  • Existing studies often describe evolutionary landscapes but lack quantitative parameter estimation from molecular data.
  • Integrating theoretical models with empirical data for clonal evolution analysis remains a challenge.

Purpose of the Study:

  • To develop a theoretical framework linking mutation rate, time, and expansion dynamics to biological/clinical parameters.
  • To infer time-resolved evolutionary parameters from molecular data, including mutation accumulation and signatures.
  • To apply this framework to understand the evolutionary history of the marbled crayfish and glioblastoma progression.

Main Methods:

  • Derived theoretical results connecting evolutionary parameters.
  • Inferred evolutionary parameters using mutation accumulation, mutational signatures, and selection analyses.
  • Applied the framework to whole-genome sequencing data from marbled crayfish and glioblastoma samples.

Main Results:

  • Predicted marbled crayfish speciation between 1986-1990, aligning with biological records.
  • Identified distinct evolutionary subgroups within glioblastoma.
  • Demonstrated that tumor cell survival dynamics can be inferred from primary tumor genomic data.

Conclusions:

  • The developed framework enables time-resolved, integrated analysis of clonal genome evolution parameters.
  • Provides novel insights into the evolutionary age of the invasive marbled crayfish.
  • Offers new perspectives on glioblastoma progression and potential for early genomic inference of tumor behavior.