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10:49
Measuring RAN Peptide Toxicity in C. elegans
Published on: April 30, 2020
Polyglutamine repeats are associated to specific sequence biases that are conserved among eukaryotes
Matteo Ramazzotti1, Elodie Monsellier, Choumouss Kamoun
1Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, Florence, Italy. matteo.ramazzotti@unifi.it
Plos One
|February 8, 2012
Summary
Protein aggregation linked to neurodegenerative diseases may be prevented by specific amino acid sequences. These sequences, found in eukaryotic proteomes, suggest evolutionary selection against harmful polyglutamine expansions.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Nine human neurodegenerative diseases are linked to protein aggregation caused by expanded polyglutamine (polyQ) tracts.
- PolyQ expansion is thought to result from polyCAG codon expansion during replication.
- However, many polyQ proteins remain soluble, suggesting counter-selection mechanisms.
Purpose of the Study:
- To identify the genetic and protein contexts that may counteract polyQ expansion and aggregation.
- To investigate evolutionary pressures shaping polyQ-containing proteins.
Main Methods:
- Developed custom software to analyze entire eukaryotic proteomes for imperfect polyQ sequences.
- Assessed amino acid residues flanking polyQ tracts and non-glutamine residues within polyQ sequences.
- Examined 15 eukaryotic proteomes for conserved amino acid biases associated with polyQ regions.
Main Results:
- Discovered significant amino acid biases associated with polyQ regions across 15 eukaryotic proteomes.
- Observed over-representation of Proline, Leucine, and Histidine, and under-representation of Aspartic acid, Cysteine, and Glycine.
- These biases are conserved across unrelated proteins and independent of protein function.
Conclusions:
- Specific amino acid residues appear to have been co-selected with polyQ sequences during evolution.
- These findings suggest a protective role for certain amino acids against polyQ expansion and aggregation.
- Further research is needed to elucidate the selective pressures driving these observed amino acid biases.
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