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

Abstract

Heterosis, the superiority of hybrids over their parents for quantitative traits, represents a crucial issue in plant and animal breeding as well as evolutionary biology. Heterosis has given rise to countless genetic, genomic and molecular studies, but has rarely been investigated from the point of view of systems biology. We hypothesized that heterosis is an emergent property of living systems resulting from frequent concave relationships between genotypic variables and phenotypes, or between different phenotypic levels. We chose the enzyme-flux relationship as a model of the concave genotype-phenotype (GP) relationship, and showed that heterosis can be easily created in the laboratory. First, we reconstituted in vitro the upper part of glycolysis. We simulated genetic variability of enzyme activity by varying enzyme concentrations in test tubes. Mixing the content of “parental” tubes resulted in “hybrids,” whose fluxes were compared to the parental fluxes. Frequent heterotic fluxes were observed, under conditions that were determined analytically and confirmed by computer simulation. Second, to test this model in a more realistic situation, we modeled the glycolysis/fermentation network in yeast by considering one input flux, glucose, and two output fluxes, glycerol and acetaldehyde. We simulated genetic variability by randomly drawing parental enzyme concentrations under various conditions, and computed the parental and hybrid fluxes using a system of differential equations. Again we found that a majority of hybrids exhibited positive heterosis for metabolic fluxes. Cases of negative heterosis were due to local convexity between certain enzyme concentrations and fluxes. In both approaches, heterosis was maximized when the parents were phenotypically close and when the distributions of parental enzyme concentrations were contrasted and constrained. These conclusions are not restricted to metabolic systems: they only depend on the concavity of the GP relationship, which is commonly observed at various levels of the phenotypic hierarchy, and could account for the pervasiveness of heterosis.

Variation for heterodimerization and nuclear localization among known and novel oil palm SHELL alleles

“…Although the data reported here do not directly prove a heterotic mechanism, we and others have postulated that heterozygosity for SHELL variants, in combination with a wild‐type Sh DeliDura allele, represents a case of single‐gene heterosis for oil yield (Singh et al , , Jin et al , ; Li et al , ; Fievet et al , ). Models proposed to account for heterosis include dominance, overdominance, pseudodominance, epistasis and dosage models involving copy number variation or polyploidy, allelic variation, gene expression differences and/or dominant negative macromolecular interactions.…”

“…In this case, the lysine to asparagine substitution encoded by sh AVROS is predicted to disrupt DNA binding, as this highly conserved lysine residue is involved in DNA binding of MADS-box proteins in other plants (Huang et al, 1996;Immink et al, 2010). Although the data reported here do not directly prove a heterotic mechanism, we and others have postulated that heterozygosity for SHELL variants, in combination with a wildtype Sh DeliDura allele, represents a case of single-gene heterosis for oil yield (Singh et al, 2013a, Jin et al, 2017Li et al, 2017;Fievet et al, 2018). Models proposed to account for heterosis include dominance, overdominance, pseudodominance, epistasis and dosage models involving copy number variation or polyploidy, allelic variation, gene expression differences and/or dominant negative macromolecular interactions.…”

Genome Sequence and QTL Analyses Using Backcross Recombinant Inbred Lines (BILs) and BILF1 Lines Uncover Multiple Heterosis-related Loci

“…A total of 10 QTLs for all of the traits were mapped independently in BIL population (Figure 4), and eight loci for the respective phenotypes were detected. Among the eight QTLs, four of these loci overlapped with QTLs detected in the BIL population, and the remaining four QTLs were detected exclusively in the BILF 1 [8,9]. These results suggest that the heading time gene strongly participates in yield heterosis in hybrid rice.…”

“…2020, 21, 780 2 of 10 heterosis has been achieved in the past decades. Three major competing but non-mutually-exclusive hypotheses (dominance, overdominance, and epistasis) have been proposed to explain heterosis at the genetic level [1][2][3][4][5][6]. However, the progress in elucidating the molecular mechanism underlying crop heterosis has lagged.…”

Heterosis indices: What do they really measure?

“…Non-linear processes are extremely common in biology. In particular, the genotype-phenotype or phenotype-phenotype relationships display frequently concave behaviours, resulting in dominance of “high” over “low” alleles (Wright, 1934) and in positive heterosis for a large diversity of polygenic traits (Fiévet et al , 2018; Vasseur et al , 2019). Quantifying properly the degree of non-additivity is an essential prerequisite for any interpretation and comparison of genetic studies and for predictions in plant and animal breeding.…”