On the biochemical basis of "aneuploid depression"

Geneticists have long noted that organisms that are either monosomic or trisomic for a particular chromosome are less vigorous than the euploid siblings (Khush, Cytogenetics of Aneuploids). The basis of this observation has been attributed to "genic unbalance." The studies of the biochemical consequences of aneuploidy reported above have possibly led to a greater understanding of this phenomenon on a biochemical level. In this report, the loss of vigor associated with aneuploidy will be referred to as "aneuploid depression."

On the biochemical level, there are two major types of effects on enzyme levels as a consequence of aneuploidy. First of all, there are gene dosage effects. That is, when segmental aneuploidy is produced for a chromosomal region that is known to carry the structural locus of a certain enzyme, the level of expression of that enzyme is directly proportional to the dosage of the chromosomal region in the dosage series. Secondly, there are inverse effects. The previous report has described the nature of this phenomenon. Basically, this effect involves a negative correlation between the dose of the chromosomal region varied and the level of an enzyme whose structural locus is not included in the aneuploid region. The data of O'Brien and Gethman (1973, Genetics 75:155) and Rawls and Lucchesi (1974, Genetical Research 24:59), for examples, illustrate these effects. When the structural loci of alpha-glycerophosphate, alcohol and isocitrate dehydrogenases were varied by segmental aneuploidy in a 1, 2, 3 relationship, the levels of these enzymes were in a respective 1, 2, 3 relationship. However, when some other segmental regions, which did not include the structural loci, were made trisomic, the enzyme level in the aneuploid was reduced relative to the euploid. The data presented in the previous report show that the inverse effect extends to segmental monosomy as well.

If a segmental aneuploid region contains both a structural gene locus and an inverse effect region that acts upon that gene, it is conceivable that the two effects would cancel each other. This cancellation would result in little net change in the level of the gene expression being monitored. The prevalence of such cancellations is unknown. The expression of ADH in the dosage series produced by TB1La (see previous report) and dosage compensation in Drosophila (see following report) may be examples.

The purpose of this note is to point out the possibility that reductions in enzyme levels may play a significant role in aneuploid depression. The above discussion has pointed out that both segmental monosomy and segmental trisomy produce reductions in the expression of sets of genes. The reductions in monosomics are due to a reduction in the number of structural genes present. The reductions in trisomics are due to an inverse effect of the aneuploid region upon the expression of a gene located elsewhere in the genome. Thus, since aneuploidy of either type causes reductions in a number of enzyme levels, a significant factor in aneuploid depression may be these reductions.

The concept that aneuploid depression is due mainly to enzyme level reductions is consistent with the fact that phenotypic mutants for which the biochemical bases are known overwhelmingly correlate a reduction of a gene product with a less vigorous phenotype (e.g. endosperm mutants; bobbed and enzyme loci in Drosophila). It is true that single gene reductions of the magnitude produced by aneuploidy are often not sufficient to reduce vigor by themselves. But we know that increasing the size of aneuploidy increases the loss of vigor (Khush, Cytogenetics of Aneuploids; Lindsley, et al., 1972, Genetics 71:157). This fact indicates that aneuploid depression is a cumulative effect of several minor components. Therefore, the loss of vigor due to aneuploidy may be the cumulative effect of the reduced expression of a number of enzymes.

The enzyme levels and vigor of the dosage series produced by TB-1La illustrate the possible correlation between aneuploid depression and enzyme reductions. The Adh gene, which is varied in this dosage series, shows a reduction in expression in the monosomic below the disomic, although it is usually not to the 50% level expected from a strict dosage effect. This intermediate value is thought to be due to a partial cancellation of a dosage effect by an inverse effect or to a limiting factor necessary for gene expression produced elsewhere in the genome. Although it is not currently known, it is conceivable that some genes included in TB-1La would show a reduction in the monosomic to 50% of the disomic level. The levels of G6PDH, 6PGDH and IDH, which are believed not to be included in the translocation, show reductions in the trisomes and tetrasomes produced by TB-1La. G6PDH is usually reduced in trisomes to about 2/3 of the disomic level and even further reduced in tetrasomes. If one considers only the reductions in enzyme levels, the vigor order of the dosage series can be explained. The vigor order is as follows from greatest to least: disomic, trisomic, tetrasomic, monosomic. This order is based on plant height and general appearance.

Although there is a correlation of enzyme reductions and vigor, one should not ignore the fact that each aneuploid also increases certain enzyme levels above the disomic value. Monosomic increases are due to a reduction of inverse effect regions; trisomic and tetrasomic increases are due to increased numbers of structural genes. Consequently, it could be argued that aneuploid depression is due to an imbalance of metabolic processes by increases OR a combination of increases and decreases. On the imbalance argument, aneuploid depression would also give a vigor order in which the aneuploids are also below the disomic.

Although the data on changes in enzyme levels in aneuploids do not allow an unequivocal discrimination of the above mentioned hypotheses, they do show that increases above euploidy usually cause decreases in the expression of sets of enzymes. The importance of the hypothesis of a correlation between aneuploid depression and reduced enzyme levels is that it allows an understanding of aneuploid depression consistent with our knowledge of the detrimental effects of single gene mutations. If this synthesis of observations is meaningful, aneuploid depression could be explained on large reductions of enzyme levels. It is reasonable, however, to propose that increases would produce stress in the cells or raise some metabolites to toxic levels. The challenge of future research is to discriminate among these alternatives, if indeed that is technically feasible or necessary.

James A. Birchler


Please Note: Notes submitted to the Maize Genetics Cooperation Newsletter may be cited only with consent of the authors.

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