On the Unknown Proteins of Eukaryotic Proteomes

Area of Science:

• Eukaryotic genomics
• Proteomics
• Bioinformatics

Background:

• Large-scale analysis of eukaryotic proteomes is crucial for understanding protein evolution and function.
• Identifying and characterizing unknown proteins, particularly singletons, presents a significant challenge in genomics.

Purpose of the Study:

• To establish a reference system for studying unknown proteins across diverse eukaryotic kingdoms.
• To analyze singletons in 362 eukaryotic proteomes and investigate their characteristics and evolutionary patterns.

Main Methods:

• Construction of a reference proteome system from 36 diverse eukaryotic proteomes.
• Analysis of 362 additional eukaryotic proteomes to identify proteins lacking known homologs (singletons).
• Utilizing Uniprot for protein knowledge and AlphaFold2 for structural predictions.

Main Results:

• A significant proportion of identified singletons are poorly characterized at the protein level (<12% known in Uniprot).
• AlphaFold2 structural predictions for singletons are generally poor due to lack of homologous sequence information.
• Metazoan species typically have fewer than 1000 singletons, while Viridiplantae and fungi show higher singleton counts, suggesting differing evolutionary timescales.

Conclusions:

• The study highlights the vast unknown protein space within eukaryotic genomes.
• The observed differences in singleton abundance suggest distinct evolutionary dynamics in protein innovation across major eukaryotic lineages.
• Further investigation with proteomes closer to the reference system is needed to confirm these evolutionary timescale hypotheses.