Non-adaptive origins of interactome complexity

Abstract

The boundaries between prokaryotes, unicellular eukaryotes, and multicellular eukaryotes are accompanied by orders-of-magnitude reductions in effective population size, with concurrent amplifications of the effects of random genetic drift and mutation1. The resultant decline in the efficiency of selection appears to be sufficient to influence a wide range of attributes at the genomic level in a nonadaptive manner2. A key remaining question concerns the extent to which variation in the power of random genetic drift is capable of influencing phylogenetic diversity at the subcellular and cellular levels2–4. Should this be the case, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. Here we demonstrate a phylogenetically broad inverse relationship between the power of drift and the structural integrity of protein subunits. This leads to the hypothesis that the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein-protein interactions that stabilize key gene functions. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by nonadaptive mechanisms.

Communication: Epistructural thermodynamics of soluble proteins

“…This epistructural tension has been estimated only recently, 6 despite its importance in determining protein associations, the basic molecular events in biological processes. A direct computation of the SSIT is difficult due to the confinement of the interfacial water within chemically and geometrically inhomogeneous nanoscale cavities 3,6 and the complications arising from the assignment of entropic costs to such confinements. To reduce the free-energy cost of spanning the interface, the SSIT promotes a highly controlled association of soluble proteins into specific complexes, while precluding proteins from amorphously precipitating to yield phase separations.…”

“…The g(r) value is computed as time average over solvent configurations determined by molecular dynamics over a 100 nsperiod after the protein structure is equilibrated with the solvent, thus allowing for breathing motions of exposed atoms. 6 Compared with bulk water (g = 4), interfacial water has reduced hydrogen-bonding opportunities (g < 4) and may counterbalance such losses by interacting with polar groups on the protein surface or with induced electrostatic fields resulting from preferred dipole alignments under confinement. 3,4 In regards to g(r) as computed in this work, only the first layer of the interface differs from bulk water, while water in outer layers invariably recapitulates bulk configurations.…”

“…Epistructural attributes of soluble proteins refer to interfacial properties arising from the physical interaction between structure and solvent and have received comparatively little attention, partly because nanoscale models of interfacial water are still in development. [1][2][3][4][5][6] The most significant epistructural parameter is the solvent-structure interfacial tension (SSIT), that is, the reversible work per unit area required to span the solvent envelope of the protein structure. This epistructural tension has been estimated only recently, 6 despite its importance in determining protein associations, the basic molecular events in biological processes.…”

“…For bulk water, we get τ = τ b ≈ 100 ps, and relaxation length τ b c = ω b −1 ≈ 0.03 m, the microwave wavelength yielding the best fit with experimental data. 6 Through the Lorentzian, the frequency dependence of bulk permittivity is subsumed into the normal distribution factor [1+(τ (r)c) 2 |ω| 2 ] −1 with τ (r) ≡ τ b .…”

“…[1][2][3][4][5][6] The most significant epistructural parameter is the solvent-structure interfacial tension (SSIT), that is, the reversible work per unit area required to span the solvent envelope of the protein structure. This epistructural tension has been estimated only recently, 6 despite its importance in determining protein associations, the basic molecular events in biological processes. A direct computation of the SSIT is difficult due to the confinement of the interfacial water within chemically and geometrically inhomogeneous nanoscale cavities 3,6 and the complications arising from the assignment of entropic costs to such confinements.…”