The thermodynamics of protein aggregation reactions may underpin the enhanced metabolic efficiency associated with heterosis, some balancing selection, and the evolution of ploidy levels

TL;DR

This paper proposes a molecular model linking protein aggregation thermodynamics to heterosis, explaining how heterozygosity enhances metabolic efficiency and influences ploidy evolution in complex organisms.

Contribution

It introduces a novel molecular dynamics model showing how protein aggregation impacts heterosis, inbreeding depression, and the evolution of organismal ploidy levels.

Findings

Heterozygosity reduces toxic protein oligomer formation.

Inbred lines decline in viability at high inbreeding coefficients.

Polyploids are favored in environments with high protein aggregation stress.

Abstract

Identifying the physical basis of heterosis (or hybrid vigor) has remained elusive despite over a hundred years of research on the subject. The three main theories of heterosis are dominance theory, overdominance theory, and epistasis theory. Kacser and Burns (1981) identified the molecular basis of dominance, which has greatly enhanced our understanding of its importance to heterosis. This paper aims to explain how overdominance, and some features of epistasis, can similarly emerge from the molecular dynamics of proteins. Possessing multiple alleles at a gene locus results in the synthesis of different allozymes at reduced concentrations. This in turn reduces the rate at which each allozyme forms soluble oligomers, which are toxic and must be degraded, because allozymes co-aggregate at low efficiencies. The model developed in this paper will be used to explain how heterozygosity can impact the metabolic efficiency of an organism. It can also explain why the viabilities of some inbred lines seem to decline rapidly at high inbreeding coefficients (F > 0.5), which may provide a physical basis for truncation selection for heterozygosity. Finally, the model has implications for the ploidy level of organisms. It can explain why polyploids are frequently found in environments where severe physical stresses promote the formation of soluble oligomers. The model can also explain why complex organisms, which need to synthesize aggregation-prone proteins that contain intrinsically unstructured regions (IURs) and multiple domains because they facilitate complex protein interaction networks (PINs), tend to be diploid while haploidy tends to be restricted to relatively simple organisms.