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

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 can explain how heterozygosity impacts 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.

Heterosis Is a Systemic Property Emerging From Non-linear Genotype-Phenotype Relationships: Evidence From in Vitro Genetics and Computer Simulations

“…Despite the multiple cases where the bases of heterosis have been clarified, some authors have been searching for a “unifying principle” (Birchler et al, 2003 ), such as genome-wide changes in DNA methylation (Tsaftaris and Polidoros, 1999 ; Shen et al, 2012 ), small RNA expression and epigenetic regulation (Ha et al, 2009 ; Groszmann et al, 2011 ; Chen, 2013 ), reduced metabolic cost of protein recycling in hybrids (Goff, 2011 ), gene dosage effects in macro-molecular complexes (Veitia and Vaiman, 2011 ), enhanced metabolic efficiency due to weak co-aggregation of allozymes (Ginn, 2017 ), mitochondrial complementation (McDaniel and Sarkissian, 1966 ; Srivastava, 1981 ) and phytohormonal expression (Rood et al, 1988 ). These molecular processes may indeed distinguish heterozygotes from homozygotes, but if they were the general hidden causes of heterosis, correlations between levels of heterosis for different traits would be observed, and this has never been reported so far (Flint-Garcia et al, 2009 ; Kaeppler, 2012 ).…”

Improved redox homeostasis owing to the up-regulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature

“…Other studies ascribe heterosis to a systemic property resulting from nonlinear concave genotype-phenotype relationships of living systems (Fiévet et al 2018;Vasseur et al 2019). Aiming to unify the theories for heterosis, a metabolic or energy-use efficiency hypothesis has been proposed (Ginn 2010(Ginn , 2017Goff 2011). Previous studies have shown that inbred organisms usually have increased rates of protein turnover relative to noninbred organisms (Hawkins et al 1986;Hedgecock et al 1996;Bayne 2004).…”

“…Previous studies have shown that inbred organisms usually have increased rates of protein turnover relative to noninbred organisms (Hawkins et al 1986;Hedgecock et al 1996;Bayne 2004). Based on theoretical biophysics calculations, Ginn (2010Ginn ( , 2017 postulated that the higher levels of protein turnover among inbred organisms can be attributed to the accumulations of misfolded and aggregated proteins that require degradation by the inbred organisms' protein quality control systems. Both protein synthesis and degradation are energy-consuming processes; inbred organisms must consume more energy to sustain a given biomass and are thus less "metabolically efficient."…”

First successful hybridization experiment between native European weatherfish (Misgurnus fossilis) and non-native Oriental weatherfish (M. anguillicaudatus) reveals no evidence for postzygotic barriers

“…"metabolic heterosis" sensu Ginn (2017)), does not show clear-cut trends: While decreased (i.e. more efficient) metabolic rates in hybrids are widely found in germinating plants (Sinha and Khanna 1975;Goff 2011), especially in crops, and could be expected based on molecular and cell physiological principles (Chen 2010(Chen , 2013Goff 2011;Ginn 2017;Govindaraju 2019), the findings in animals are controversial. In marine bivalves Hedgecock et al (1996) observed more efficient protein metabolism coupled with lower oxygen consumption in three out of four replicate experiments, whereas in geckos lower SMR was observed in hybrids in only one out of three regions (Kearney and Shine 2004).…”