One million years of solitude: the rapid evolution of de novo protein structure and complex

Recent studies have established that de novo genes, evolving from non-coding sequences, enhance protein diversity through a stepwise process. However, the pattern and rate of their structural evolution over time remain unclear. Here, we addressed these issues within a short evolutionary timeframe ([~]1 million years for 97% of rice de novo genes). We found that de novo genes evolve faster than gene duplicates in the intrinsic disordered regions (IDRs, such as random coils), secondary structural elements (such as -helix and {beta}-strand), hydrophobicity, and molecular recognition features (MoRFs). Specifically, we observed an 8-14% decay in random coils and IDR lengths per million years per protein, and a 2.3-6.5% increase in structured elements, hydrophobicity, and MoRFs. These patterns of structural evolution align with changes in amino acid composition over time. We also revealed significantly higher positive charges but smaller molecular weights for de novo proteins than duplicates. Tertiary structure predictions demonstrated that most de novo proteins, though not typically well-folded on their own, readily form low-energy and compact complexes with extensive residue contacts and conformational flexibility, suggesting "a faster-binding" scenario in de novo proteins to promote interaction. Our findings illuminate the rapid evolution of protein structure in the early life of de novo proteins in rice genome, originating from noncoding sequences, highlighting their quick transformation into active, complex-forming components within a remarkably short evolutionary timeframe.