High GC content causes orphan proteins to be intrinsically disordered

Area of Science:

• Evolutionary biology
• Genomics
• Biochemistry

Background:

• The de novo creation of protein-coding genes from noncoding regions results in orphan proteins.
• Fixation of these orphan proteins in a population suggests selective pressure, but the forces involved remain unclear.
• Contradictory trends in protein disorder (younger proteins being more disordered) observed in Drosophila versus yeast lack a definitive explanation.

Purpose of the Study:

• To investigate the selective pressures acting on newly evolved orphan proteins.
• To explain the divergent trends in protein disorder and age observed across different species.
• To elucidate the relationship between protein properties, evolutionary age, and genomic features.

Main Methods:

• Analysis of protein structural properties and evolutionary age across 187 eukaryotic organisms.
• Statistical examination of correlations between protein characteristics, GC content, and age.
• Comparative analysis of protein properties in species with differing GC content, such as Drosophila and yeast.

Main Results:

• Protein properties, excluding length, show minimal variation with age across most eukaryotes.
• GC content significantly influences the observed trends in protein disorder, explaining the differences between yeast and Drosophila.
• GC content is correlated with amino acid composition that promotes intrinsic disorder.

Conclusions:

• Intrinsic disorder is not a primary determinant for the fixation of orphan proteins.
• Orphan protein properties largely resemble those of random proteins, modulated by the organism's GC content.
• The observed evolutionary trends in protein disorder are reconciled by considering GC content, rather than intrinsic disorder alone, as a key factor.