Physical Constraints on Epistasis

Abstract Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we demonstrate that the physical dynamics of a biological system can generically constrain epistasis...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular biology and evolution 2020-10, Vol.37 (10), p.2865-2874
Hauptverfasser: Husain, Kabir, Murugan, Arvind
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext bestellen
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Abstract Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we demonstrate that the physical dynamics of a biological system can generically constrain epistasis. We analyze models and experimental data on proteins and regulatory networks. In each, we find that if the long-time physical dynamics is dominated by a slow, collective mode, then the dimensionality of mutational effects is reduced. Consequently, epistatic coefficients for different combinations of mutations are no longer independent, even if individually strong. Such epistasis can be summarized as resulting from a global nonlinearity applied to an underlying linear trait, that is, as global epistasis. This constraint, in turn, reduces the ruggedness of the sequence-to-function map. By providing a generic mechanistic origin for experimentally observed global epistasis, our work suggests that slow collective physical modes can make biological systems evolvable.
ISSN:0737-4038
1537-1719
DOI:10.1093/molbev/msaa124