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Coding Sequence Insertions in Fungal Genomes are Intrinsically Disordered and can Impart Functionally-Important

Bernard D Lemire1, Priya Uppuluri2,3

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Summary

Insertion and deletion mutations (indels) generate protein diversity. Fungal proteome analysis reveals over 30,000 insertions, including clade-defining insertions (CDIs), impacting protein function and evolution.

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Area of Science:

  • * Molecular Biology
  • * Evolutionary Biology
  • * Fungal Genetics

Background:

  • * Insertion and deletion mutations (indels) are key drivers of protein diversity and functional evolution.
  • * Previous work identified specific NDU1 protein insertions in *Candida albicans* as crucial for respiration, biofilm formation, and pathogenesis, highlighting their potential as drug targets.
  • * Indels in coding sequences face selective pressure to maintain reading frames and protein function, yet provide raw material for new properties.

Approach:

  • * Comprehensive analysis of indels and clade-defining insertions (CDIs) across 80 ascomycete proteomes, including CTG clade, Saccharomycetaceae, Aspergillaceae, and Herpotrichiellaceae families.
  • * Identification and characterization of over 30,000 insertions, 4,000 CDIs, and 2,500 clade-defining deletions (CDDs) with varying lengths.
  • * Investigation of insert characteristics, including over-representation in protein kinases, exclusion from structural domains, predicted disorder, and amino acid composition (depleted hydrophobic, enriched polar residues).

Key Points:

  • * Over 30,000 insertions and 2,500 clade-defining deletions (CDDs) were identified in fungal proteomes.
  • * Inserts are frequently found in protein kinases, are predicted to be disordered, and are enriched in polar amino acids.
  • * A specific indel in *Saccharomyces cerevisiae* Sth1 protein transitions from disordered to a beta-strand upon interaction, influencing transcriptional regulation.

Conclusions:

  • * Indels and CDIs are significant factors shaping fungal proteomes and protein function.
  • * The distinct properties of fungal indels suggest roles in adaptation and evolutionary innovation.
  • * Understanding indel mechanisms, like the Sth1 example, can reveal novel regulatory pathways and potential therapeutic targets.