The physical basis and practical consequences of biological promiscuity

Abstract

Proteins interact with metabolites, nucleic acids, and other proteins to orchestrate the myriad catalytic, structural and regulatory functions that support life, from the simplest microbes to the most complex multicellular organisms. These molecular interactions are often exquisitely specific, but never perfectly so. Adventitious 'promiscuous' interactions are ubiquitous due to the thousands of macromolecules and small molecules crowded together in cells. Such interactions may perturb protein function at the molecular level, but as long as they do not compromise organismal fitness, they will not be removed by natural selection. Although promiscuous interactions are physiologically irrelevant, they are important because they provide a vast pool of potential functions that can act as the starting point for the evolution of new functions, both in nature and in the laboratory.

Functional Long Non-coding RNAs Evolve from Junk Transcripts

“…Promotes Generation of Junk RNA Another concept that is commonly glossed over is that the production of a low level of junk RNA is fully compatible with our current understanding of biochemistry. All enzymes as well as regulatory proteins possess a degree of promiscuity and can bind to, and act on, sub-optimal substrates (Copley, 2020;Tawfik, 2020). Thus, transcription factors, which typically recognize short degenerate DNA motifs, will bind not only to gene-regulatory regions, but also to many additional non-functional sites in the genome (Paris et al, 2013;Reilly and Noonan, 2016;Villar et al, 2014;Wong et al, 2015).…”

General theory of specific binding: insights from a genetic-mechano-chemical protein model

“…The strength of these bonds is given by 𝜀 𝑠 > 𝜀 𝑤 depending on the sequence; the binding constant is 𝜀 𝑠 or 𝜀 𝑤 respectively for w 𝑐 or s 𝑐 . The largest protein studied has 𝑁 𝐴 = 22, so the world of such proteins therefore has at most 2 22 • 2 3 possibilities. This size restriction allows us to compute all quantities for the entire genome.…”

Not functional yet a difference maker: junk DNA as a case study

“…As we discussed in "Junk DNA" section, junk DNA also provides additional, nonspecific substrates for enzymes in the cell to engage with. All enzymes have a preferred substrate, but they will act on non-optimal substrates as well, especially when subjected to non-adaptive evolutionary pressures (Khersonsky and Tawfik 2010;Bar-Even et al 2011;Tawfik 2020;Copley 2020). Normally the amount of activity associated with these non-optimal substrates is negligible; however, when the amount of non-optimal substrate is in vast excess of the preferred substrate, nonoptimal reactions can become substantial.…”