RT Journal Article SR Electronic T1 One million years of solitude: the rapid evolution of de novo protein structure and complex JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.12.24.573215 DO 10.1101/2023.12.24.573215 A1 Chen, Jianhai A1 Li, Qingrong A1 Xia, Shengqian A1 Arsala, Deanna A1 Sosa, Dylan A1 Wang, Dong A1 Long, Manyuan YR 2023 UL http://biorxiv.org/content/early/2023/12/26/2023.12.24.573215.abstract AB 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 α-helix and β-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.Competing Interest StatementThe authors have declared no competing interest.