Molecular basis of heterosis
The classic quantitative genetic explanations for heterosis center on two concepts . The first is “dominance,” which originally meant that heterosis results from the complementation in the hybrid of different deleterious alleles that were present in the inbred parental lines by superior alleles from the opposite parent. Over time, this term came to mean the degree to which the heterozygous genotype performs differently from the mean of the two homozygous classes. The second historical explanation for heterosis is “over dominance,” which refers to the idea that allelic interactions occur in the hybrid such that the heterozygous class performs better than either homozygous class. Although these terms have developed a following in each case, they both now refer to non additive situations, differing in degree. These terms were coined before the molecular concepts of genetics were formulated and are not connected with molecular principles. Therefore, they are of diminished utility for describing the molecular parameters that accompany heterosis. At the molecular level, one can envision two extreme models to explain heterosis. In the first case, one might imagine that in the hybrid, when the two different alleles of various genes are brought together, there is a combined allelic expression. In the second model, the combination of different alleles produces an interaction that causes gene expression in the hybrid to deviate relative to the mid parent predictions (e.g., by an up regulation of many housekeeping genes). This scenario might best be considered the result of regulatory gene allelic interactions. Indeed, a recent article by Song and Messing (2003), described in more detail below, provides evidence for altered regulatory effects in hybrids. The challenge in the development of a molecular model for heterosis is to make the correct associations between phenotype and any causative molecular events that occur in hybrids. [3] The preferred explanation for heterosis during the past century was that the two inbred lines contain different slightly deleterious alleles at multiple loci. When the hybrid is produced, all mutations are complemented, generating progeny that exceed either parent. An early criticism of this idea was that if this hypothesis were true, it should be possible to create an inbred line with all of the superior alleles, showing little or no hybrid vigor a situation that has not occurred. The counter argument stated that, with so many genes involved, it would be impossible to accumulate all of the better alternatives into one line as a result of the linkage of the deleterious alleles with superior alleles of other genes. Although it is true that any deleterious alleles would become homozygous in different inbred lines and that the hybrid would show complementation for these genes, this fact might account only for the hybrid being equivalent to the better of the two parents for the effect of any individual gene. Alternatively, if the complementation of alleles in different genes were cumulative in the phenotype, then heterosis would result. The molecular question to be addressed is whether the simple complementation of different slightly deleterious alleles generates a growth response that can explain heterosis. However, several observations regarding heterosis suggest that the basic principle of heterosis is something other than simple complementation. The first observation to suggest a basis other than simple complementation is that although inbred lines have been improved greatly over the decades, the magnitude of heterosis has not diminished but has increased slightly. If heterosis were caused by the complementation of deleterious alleles and in breadlines have been purged of the most severe of such alleles, then the absolute amount of heterosis might be expected to decline somewhat. Selection for better inbred lines has improved the vigor of plants, but it has done less to change the magnitude of heterosis. In other words, heterosis gives the appearance of being more resistant to artificial selection than the quality of inbred lines themselves. Furthermore, the quality of two inbred lines does not necessarily predict the amount of heterosis; this must be determined in a cross. These observations suggest that instead of replacing alleles of genes that modulate physiological processes important for heterosis, the slight increase in hybrid vigor over the years might have occurred by selecting alleles at the right set of loci that produce the best combinations in hybrids to bring about heterosis. [5]
A second observation about heterosis that argues against simple complementation is progressive heterosis in tetraploids. At the diploid level, only two alleles of a gene can occur in an individual, but at higher ploidy levels, a variety of allelic combinations are possible for any one gene. In autotetraploids that are hybrid between two inbred lines (alleles designated AABB), heterosis occurs, but it is typically greater when there are potentially three or four different alleles present at the various loci (designated ABCD). Even in allohexaploid wheat, in which three different genomes contribute to the genetic constitution, hybrids between diverse varieties exhibit heterosis. It appears that vigor improves with the greater number of distinct genomes present. For simple complementation to explain progressive heterosis, each new step-wise combination of genomes would need to supply increasingly superior alleles to complement the preexisting rate-limiting alleles without introducing deleterious alleles at other loci. The probability that this situation would occur is quite low. A release from a negative dosage effect on vigor by identical alleles could account for progressive heterosis, as discussed further below. [4]
The third observation to consider is that inbreeding depression (the decline in vigor over several generations of selfing) in tetraploids of many species proceeds faster than expected based on the homozygosis of alleles. In a diploid, selfing of a heterozygote (A/B) will produce half of the progeny that are homozygous at any one locus and the other half that regenerate the heterozygous situation. In an autotetraploid, the selfing of a heterozygote (A/A/B/B) will produce homozygotes (A/A/A/A or B/B/B/B) at any one locus in only ≈1 of 18 offspring (depending on the degree of linkage to the centromere). In addition to A/A/B/B heterozygotes being formed again, A/A/A/B and B/B/B/A heterozygotes are present in the population. Despite this difference in the rate of progression to homozygosity, the trajectory of inbreeding depression in tetraploids often is faster than predicted and not very different from that in diploids. In some species, tetraploid inbreeding depression proceeds faster than at the diploid level. As discovered by Randolph (1942), tetraploid derivatives of inbred maize lines often are less vigorous than the diploid progenitor. Thus, in this species, the end product of inbreeding depression in tetraploids is less than that of diploids, even though the genotype is identical (but differs in dosage).One resolution of this finding is to suggest that allelic dosage plays a more important role in tetraploids for generating inbreeding depression than does complete homozygosis itself, because the allelic dosage shifts more rapidly than homozygosis during selfing. The increasing number of identical alleles appears to have a negative dosage effect on vigor.
Figure 1. Heterosis in Maize.
Representative individuals from two inbred maize lines (B73 [far left] and Mo17 [far right]) and the progeny of reciprocal hybrid crosses (B73/Mo17 [left center] and Mo17/B73 [right center]; the female parent is listed first in maize genetics nomenclature) are shown. B73 and Mo17 are two high-quality inbred lines. Nonetheless, the progeny of a hybrid cross between these two lines are taller and more productive than either parent, illustrating the concept of heterosis.
If there is any involvement of a dosage effect of alleles in polyploid heterosis, this realization is gratifying given that the bulk of quantitative trait loci show some degree of semidominant behavior, indicating that the control of quantitative characters is largely affected by multiple loci that exhibit an allelic dosage effect. The results of aneuploid studies likewise indicate that quantitative characteristics are affected by multiple dosagedependent genes. There is likely a connection between these two observations. [9]