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Assessing conservation of alternative splicing with evolutionary splicing graphs.

Diego Javier Zea1, Sofya Laskina2, Alexis Baudin3

  • 1Sorbonne Université, CNRS, IBPS, Laboratoire de Biologie Computationnelle et Quantitative (LCQB), 75005 Paris, France.

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Summary

This study introduces a novel method to analyze evolutionary transcript variability using parsimonious evolutionary splicing graphs. This approach links alternative splicing to gene function, regulation, and conservation across species.

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Bioinformatics

Background:

  • Understanding protein evolution is crucial for human genetics and medicine.
  • Transcript variability and alternative splicing play key roles in biological complexity.

Purpose of the Study:

  • To develop a method for describing and analyzing whole transcript variability across species.
  • To construct parsimonious evolutionary splicing graphs.

Main Methods:

  • Generalized the definition of splicing graphs.
  • Constructed parsimonious evolutionary splicing graphs with species-wide minimal transcript building blocks.
  • Analyzed functional relevance, tissue regulation, and conservation of alternative transcripts.

Main Results:

  • Established a link between alternative transcripts, their function, regulation, and conservation in 50 genes.
  • Identified thousands of human protein-coding genes where alternative splicing affects pseudorepeat composition.
  • Developed ThorAxe, an efficient computational tool for this analysis.

Conclusions:

  • The developed method provides insights into the evolution and diversification of protein function.
  • Alternative splicing significantly modulates gene structure and function across the human genome.
  • ThorAxe offers a robust and accessible tool for evolutionary transcriptomics research.