Most highly expressed protein-coding genes have a single dominant isoform.

Area of Science:

• Genomics
• Proteomics
• Molecular Biology

Background:

• Eukaryotic cells produce numerous alternatively spliced transcripts.
• The expression patterns of these transcripts across tissues remain unclear, with conflicting research findings.
• It is unknown if genes predominantly express a single dominant splice variant or multiple isoforms simultaneously.

Purpose of the Study:

• To investigate whether genes express a dominant splice variant at the protein level.
• To determine if dominant protein isoforms are tissue-specific or universally expressed.
• To reconcile conflicting results from previous large-scale transcriptomic studies.

Main Methods:

• Analysis of peptides from eight large-scale human proteomics experiments and databases.
• Interrogation of protein-level data to identify dominant isoforms.
• Comparison of experimentally identified dominant isoforms with reference isoforms from consensus coding sequence variants and the APPRIS database.

Main Results:

• The vast majority of protein-coding genes exhibit a single dominant protein isoform.
• This dominant isoform is consistent across different tissues and cell types.
• Experimental proteomics findings largely agreed with reference isoforms from consensus coding sequences and APPRIS.

Conclusions:

• Genes predominantly express a single dominant protein isoform, irrespective of cellular or tissue context.
• This suggests a conserved and stable protein expression landscape in humans.
• The findings support the validity of reference isoform selections in genomic databases.