The implications of gene heterozygosity for protein folding and protein turnover

Ginn, Brian R.

doi:10.1016/j.jtbi.2010.05.023

Cited by 7 publications

(14 citation statements)

References 156 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, the result of our study is in agreement with the energy-use efficiency hypothesis (Ginn 2010(Ginn , 2017Goff 2011). This hypothesis was proposed mainly based on the observation that inbred organisms usually have increased rates of protein turnover relative to noninbred organisms (Hawkins et al 1986;Hedgecock et al 1996;Bayne 2004).…”

Section: Discussionsupporting

confidence: 92%

“…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).…”

mentioning

confidence: 99%

“…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."…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2021

View full text Add to dashboard Cite

Heterosis or hybrid vigor is a common phenomenon in plants and animals; however, the molecular mechanisms underlying heterosis remain elusive, despite extensive studies on the phenomenon for more than a century. Here we constructed a large collection of F1 hybrids of Saccharomyces cerevisiae by spore-to-spore mating between homozygous wild strains of the species with different genetic distances and compared growth performance of the F1 hybrids with their parents. We found that heterosis was prevalent in the F1 hybrids at 40°C. A hump-shaped relationship between heterosis and parental genetic distance was observed. We then analyzed transcriptomes of selected heterotic and depressed F1 hybrids and their parents growing at 40°C and found that genes associated with one-carbon metabolism and related pathways were generally up-regulated in the heterotic F1 hybrids, leading to improved cellular redox homeostasis at high temperature. Consistently, genes related with DNA repair, stress responses, and ion homeostasis were generally down-regulated in the heterotic F1 hybrids. Furthermore, genes associated with protein quality control systems were also generally down-regulated in the heterotic F1 hybrids, suggesting a lower level of protein turnover and thus higher energy use efficiency in these strains. In contrast, the depressed F1 hybrids, which were limited in number and mostly shared a common aneuploid parental strain, showed a largely opposite gene expression pattern to the heterotic F1 hybrids. We provide new insights into molecular mechanisms underlying heterosis and thermotolerance of yeast and new clues for a better understanding of the molecular basis of heterosis in plants and animals.

show abstract

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Both Kristensen et al (2002) and Goff (2011) argued that these previous findings can be explained if homozygosity for deleterious mutations leads to greater expression of unstable proteins by inbred individuals. In contrast, Ginn (2010) attempted to show that the previous findings could be explained by an overdominance model if protein aggregation is assumed to be a highly specific process (see below). Mead et al (2003) had already shown that the specificity of prion amyloid formation resulted in balancing selection at the prion protein gene.…”

Section: Introductionmentioning

confidence: 99%

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

Ginn

2017

Progress in Biophysics and Molecular Biology

View full text Add to dashboard Cite

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.

show abstract

“…In summary, this paper describes a model for heterosis that is relatively simple, consistent with a number of diverse observations from a variety of species, and provides an obvious route toward crop enhancement. Recently, Brian Ginn authored an article in the Journal of Theoretical Biology describing the importance of protein stability in heterosis, although the proposed mechanism differs from allele‐specific expression described here (Ginn, 2010). Ginn proposes that ‘The accumulation of misfolded and aggregated proteins within inbred organisms are the result of more negative free energies of folding for proteins encoded at homozygous gene loci and higher concentrations of potentially aggregating non‐native protein species within the cell’.…”

Section: Putting the Model To Workmentioning

confidence: 91%

A unifying theory for general multigenic heterosis: energy efficiency, protein metabolism, and implications for molecular breeding

2010

View full text Add to dashboard Cite

SummaryHybrids between genetically diverse varieties display enhanced growth, and increased total biomass, stress resistance and grain yield. Gene expression and metabolic studies in maize, rice and other species suggest that protein metabolism plays a role in the growth differences between hybrids and inbreds. Single trait heterosis can be explained by the existing theories of dominance, overdominance and epistasis. General multigenic heterosis is observed in a wide variety of different species and is likely to share a common underlying biological mechanism. This review presents a model to explain differences in growth and yield caused by general multigenic heterosis. The model describes multigenic heterosis in terms of energy-use efficiency and faster cell cycle progression where hybrids have more efficient growth than inbreds because of differences in protein metabolism. The proposed model is consistent with the observed variation of gene expression in different pairs of inbred lines and hybrid offspring as well as growth differences in polyploids and aneuploids. It also suggests an approach to enhance yield gains in both hybrid and inbred crops via the creation of an appropriate computational analysis pipeline coupled to an efficient molecular breeding program.

show abstract

The implications of gene heterozygosity for protein folding and protein turnover

Cited by 7 publications

References 156 publications

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

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

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

A unifying theory for general multigenic heterosis: energy efficiency, protein metabolism, and implications for molecular breeding

Contact Info

Product

Resources

About