Comparative genomics reveals long, evolutionarily conserved, low-complexity islands in yeast proteins

Area of Science:

• Evolutionary biology
• Genomics
• Proteomics

Background:

• Eukaryotic proteomes contain numerous low-complexity sequences (LCS), such as tandem repeats and compositionally biased regions.
• The functional significance of these LCS remains largely unexplored, particularly in yeast.

Purpose of the Study:

• To investigate the functional importance of compositionally biased sequences in the yeast proteome.
• To differentiate between functionally constrained and neutrally evolving LCS using evolutionary analysis.

Main Methods:

• Comparative genomic analysis of 2838 orthologous open reading frame (ORF) families across three Saccharomyces species.
• Quantification of sequence conservation using amino acid variability and nonsynonymous-to-synonymous substitution ratios (Ka/Ks).
• Application of a neutral Poisson model to identify conserved LCS.

Main Results:

• 1033 ORF families contained long (≥45 residues) low-complexity islands.
• LCS were generally less conserved than entire ORFs, showing higher variability and Ka/Ks ratios.
• Conserved LCS were significantly enriched in ORFs encoding nucleic acid binding proteins, cytoskeleton components, and intracellular transporters.

Conclusions:

• Most LCS evolve neutrally, but a subset exhibits significant conservation, indicating functional importance.
• Comparative genomics is crucial for identifying functionally relevant LCS amidst neutral variation.
• Conserved LCS are often associated with critical cellular roles, even when their specific functions are uncharacterized.