Effects of Aneuploidy on Genome Structure, Expression, and Interphase Organization in Arabidopsis thaliana

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Abstract
Aneuploidy refers to losses and/or gains of individual chromosomes from the normal chromosome set. The resulting gene dosage imbalance has a noticeable affect on the phenotype, as illustrated by aneuploid syndromes, including Down syndrome in humans, and by human solid tumor cells, which are highly aneuploid. Although the phenotypic manifestations of aneuploidy are usually apparent, information about the underlying alterations in structure, expression, and interphase organization of unbalanced chromosome sets is still sparse. Plants generally tolerate aneuploidy better than animals, and, through colchicine treatment and breeding strategies, it is possible to obtain inbred sibling plants with different numbers of chromosomes. This possibility, combined with the genetic and genomics tools available for Arabidopsis thaliana, provides a powerful means to assess systematically the molecular and cytological consequences of aberrant numbers of specific chromosomes. Here, we report on the generation of Arabidopsis plants in which chromosome 5 is present in triplicate. We compare the global transcript profiles of normal diploids and chromosome 5 trisomics, and assess genome integrity using array comparative genome hybridization. We use live cell imaging to determine the interphase 3D arrangement of transgene-encoded fluorescent tags on chromosome 5 in trisomic and triploid plants. The results indicate that trisomy 5 disrupts gene expression throughout the genome and supports the production and/or retention of truncated copies of chromosome 5. Although trisomy 5 does not grossly distort the interphase arrangement of fluorescent-tagged sites on chromosome 5, it may somewhat enhance associations between transgene alleles. Our analysis reveals the complex genomic changes that can occur in aneuploids and underscores the importance of using multiple experimental approaches to investigate how chromosome numerical changes condition abnormal phenotypes and progressive genome instability. Most plants and animals have two copies of each chromosome in the normal chromosome set. Unbalanced numerical changes resulting from gains or losses of individual chromosomes (aneuploidy) usually have deleterious consequences. For example, Down syndrome in humans is caused by an extra (triplicate) copy of chromosome 21. Human tumor cells usually display numerous alterations in chromosome number and structure. Little is known about how changes in chromosome number influence gene activity and chromosome integrity, thereby perturbing physiology and development. We have used the model plant A. thaliana to study how triplication of chromosome 5 affects gene expression, chromosome structure, and chromosome packaging in the nucleus. The results indicate that the presence of an extra chromosome 5 has multiple effects: (1) substantial changes in gene expression occur, primarily on the triplicated chromosome 5 but also on the four non-triplicated chromosomes; (2) broken derivatives of chromosome 5 can be retained in the presence of two normal copies; and (3) two copies of the triplicated chromosome 5 may show a slightly enhanced tendency to associate with each other, perhaps to spatially compensate for the chromosome imbalance. The detrimental effects of aneuploidy are likely due to concurrent changes in gene expression, chromosome structure, and arrangement.