Buffering of Segmental and Chromosomal Aneuploidies in Drosophila melanogaster

Abstract

Chromosomal instability, which involves the deletion and duplication of chromosomes or chromosome parts, is a common feature of cancers, and deficiency screens are commonly used to detect genes involved in various biological pathways. However, despite their importance, the effects of deficiencies, duplications, and chromosome losses on the regulation of whole chromosomes and large chromosome domains are largely unknown. Therefore, to explore these effects, we examined expression patterns of genes in several Drosophila deficiency hemizygotes and a duplication hemizygote using microarrays. The results indicate that genes expressed in deficiency hemizygotes are significantly buffered, and that the buffering effect is general rather than being mainly mediated by feedback regulation of individual genes. In addition, differentially expressed genes in haploid condition appear to be generally more strongly buffered than ubiquitously expressed genes in haploid condition, but, among genes present in triploid condition, ubiquitously expressed genes are generally more strongly buffered than differentially expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest general mechanisms have evolved that stimulate or repress gene expression of aneuploid regions as appropriate, and on the 4th chromosome of Drosophila this compensation is mediated by Painting of Fourth (POF).

Female mice lacking Xist RNA show partial dosage compensation and survive to term

“…Although X-linked gene expression is significantly increased, the overall increase is far less than expected of two active X chromosomes. These data thereby provide support for inherent genome balance and "inverse effects" as historically observed in plants and flies (Stenberg et al 2009;Birchler 2013;Sun et al 2013). However, they also demonstrate that small deviations from X-autosomal equivalence can have a major impact on survival and fitness.…”

Aneuploidy Causes Tissue-Specific Qualitative Changes in Global Gene Expression Patterns in Maize

“…Interestingly, the expression level for most of the studied genes showed tissue-specific differences in response to aneuploidy. Only recently, global gene expression profiling studies have been performed in aneuploid tissues from human and mouse (Mao et al, 2003(Mao et al, , 2005Kahlem et al, 2004;Lyle et al, 2004;FitzPatrick, 2005;Ait Yahya-Graison et al, 2007;Laffaire et al, 2009), Drosophila flies (Stenberg et al, 2009), Arabidopsis (Arabidopsis thaliana; Huettel et al, 2008), and maize seedlings (Makarevitch et al, 2008). Several models explaining the effects of aneuploidy on global gene expression have been proposed FitzPatrick, 2005;Birchler and Veitia, 2007).…”

“…Such a response in trans can lead to large quantitative differences in gene expression (up-regulation as well as down-regulation) or even qualitative changes in gene expression patterns and affect many genes due to complex gene interactions. All of the studies assaying global gene expression in aneuploids reported trans-effects as well as some level of functional gene dosage compensation, or a "buffering" effect, when the level of RNA transcript read from genes present in three copies due to segmental aneuploidy were found to be similar to wild-type levels (Mao et al, 2003(Mao et al, , 2005Kahlem et al, 2004;Lyle et al, 2004;FitzPatrick, 2005;Potier et al, 2006;Ait Yahya-Graison et al, 2007;Huettel et al, 2008;Makarevitch et al, 2008;Moldrich et al, 2009;Stenberg et al, 2009). The degree of reported dosage compensation varied substantially between studies: from 3% to 15% in Arabidopsis (Huettel et al, 2008) and developing human brain cells (Mao et al, 2003(Mao et al, , 2005 to over 65% in human lymphoblastoid cells (Ait Yahya-Graison et al, 2007).…”

The Causes and Consequences of Aneuploidy in Eukaryotic Cells

“…Similarly, microarray analysis of mRNA levels revealed a gene-dosage dependent increase of mRNA levels of genes encoded on the extra chromosomes, as well as other deregulations, but no specific expression pattern in these trisomic MEFs [39]. Analysis of transcriptional data from Drosophila cells with various segmental and chromosomal aneuploidies identified no general response to the chromosome number changes [45,46]. Thus, further research will be required to address the question whether all eukaryotic cells show a unified response to aneuploidy, or whether this is something to be observed only in budding yeast.…”

“…Using Drosophila as another excellent model for analysis of the effects of aneuploidy, recent research revealed a significant buffering of genes in aneuploid regions [45,46]. The authors also identified that the buffering is more efficient for differentially expressed genes than for genes that are expressed ubiquitously.…”