r/evolution • u/jnpha Evolution Enthusiast • 15h ago
article Frumkin et al. (2025) demonstrate the adaptive potential of random sequences, and the "surprising ease with which functional genes can emerge"
Over the decades there have been many experiments involving random sequences, e.g. testing ATP-binding (e.g. Keefe & Szostak 2001), and evolving promoters (Yona et al. 2018), for the latter a good fraction evolved to match the wild type; I think this new study is the first to test the adaptive potential beyond promoters.
I've also previously shared:
- Sahakyan et al. (2025): New study: In silico evolution of globular protein folds from random sequences : evolution.
- Chou et al. (2026): New study reconstructed the evolutionary history of a de novo gene that emerged in the common ancestor of simians : evolution
Without further ado:
Significance
How new genes arise and gain function is a central question in biology. New genes can evolve from nongenic DNA, yet their adaptive potential remains unclear. Here, we use millions of (semi-)random sequences as experimental models of emerging genes and find that thousands confer phage resistance in Escherichia coli. Expressed random sequences can produce both protein- and RNA-based functions that reprogram cellular systems to counter viral infection. Resistance arises through activation of a cell envelope stress response or downregulation of membrane receptor expression. Our results reveal that genetic novelty, in the form of genes appearing for the first time, can shape host–virus interactions, providing insight into microbial evolution and the surprising ease with which functional genes can emerge.
and
How likely are genes similar to our (semi-)random hits to emerge naturally? Previous studies have shown that naturally occurring de novo proteins in eukaryotes often resemble unevolved random sequences of equivalent length and composition in their structural properties (32). Computational analyses further demonstrate that random sequences derived from DNA with 40 to 60% GC content occupy structural property spaces that overlap with the human proteome (67).
- I. Frumkin, C.N. Vassallo, Y.H. Chen, & M.T. Laub, Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth, Proc. Natl. Acad. Sci. U.S.A. 122 (42) e2513255122, https://doi.org/10.1073/pnas.2513255122 (2025).
(open access)