Proteins of Unknown Biochemical Function: A Persistent Problem and a Roadmap to Help Overcome It

Area of Science:

• Genomics
• Bioinformatics
• Comparative Genomics

Background:

• Genome sequencing is accelerating, but functional gene annotation remains a significant bottleneck.
• In plants like Arabidopsis thaliana, a substantial proportion of enzyme- and transporter-encoding genes lack credible functional annotations, particularly in nonmodel species.

Purpose of the Study:

• To address the challenge of functional characterization for unknown genes in plant genomes.
• To explore strategies for improving the efficiency and accuracy of gene function prediction.

Main Methods:

• Mining existing databases for protein localization and coexpression data.
• Employing cross-kingdom comparative genomics, particularly leveraging homologous microbial genes.
• Utilizing genetically tractable microbes for preliminary functional testing of predicted genes.

Main Results:

• Approximately 40% of enzyme- and transporter-encoding genes in Arabidopsis have credible annotations; this percentage is lower in nonmodel plants.
• About half of the genes encoding unknown enzymes and transporters in Arabidopsis possess microbial homologs, highlighting the potential of cross-kingdom comparisons.
• Preliminary tests in microbes can help prioritize genes for costly and specialized biochemical validation.

Conclusions:

• Cross-kingdom comparative genomics offers a powerful approach to complement plant-based data for gene function discovery.
• Integrating evidence from various sources, including microbial homologs and experimental data, strengthens functional predictions.
• Utilizing microbial systems can streamline the validation process for gene function, reducing the cost and resource demands of biochemical studies.