Dosage compensation can buffer copy-number variation in wild yeast

Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at 10–30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.

Download Full-text

Author response: Dosage compensation can buffer copy-number variation in wild yeast

10.7554/elife.05462.023 ◽

2015 ◽

Author(s):

James Hose ◽

Chris Mun Yong ◽

Maria Sardi ◽

Zhishi Wang ◽

Michael A Newton ◽

...

Keyword(s):

Copy Number Variation ◽

Dosage Compensation ◽

Copy Number ◽

Author Response ◽

Wild Yeast ◽

Number Variation

Download Full-text

Decision letter: Dosage compensation can buffer copy-number variation in wild yeast

10.7554/elife.05462.022 ◽

2015 ◽

Keyword(s):

Copy Number Variation ◽

Dosage Compensation ◽

Copy Number ◽

Wild Yeast ◽

Number Variation

Download Full-text

Correction: Dosage compensation can buffer copy-number variation in wild yeast

eLife ◽

10.7554/elife.15743 ◽

2016 ◽

Vol 5 ◽

Author(s):

James Hose ◽

Chris Mun Yong ◽

Maria Sardi ◽

Zhishi Wang ◽

Michael A Newton ◽

...

Keyword(s):

Copy Number Variation ◽

Dosage Compensation ◽

Copy Number ◽

Wild Yeast ◽

Number Variation

Download Full-text

Genome plasticity in Paramecium bursaria revealed by population genomics

BMC Biology ◽

10.1186/s12915-020-00912-2 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Yu-Hsuan Cheng ◽

Chien-Fu Jeff Liu ◽

Yen-Hsin Yu ◽

Yu-Ting Jhou ◽

Masahiro Fujishima ◽

...

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Population Genomics ◽

Gene Dosage ◽

Gene Copy Number ◽

Paramecium Bursaria ◽

Gene Copy ◽

Genome Plasticity ◽

Ciliate Species ◽

Number Variation

Abstract Background Ciliates are an ancient and diverse eukaryotic group found in various environments. A unique feature of ciliates is their nuclear dimorphism, by which two types of nuclei, the diploid germline micronucleus (MIC) and polyploidy somatic macronucleus (MAC), are present in the same cytoplasm and serve different functions. During each sexual cycle, ciliates develop a new macronucleus in which newly fused genomes are extensively rearranged to generate functional minichromosomes. Interestingly, each ciliate species seems to have its way of processing genomes, providing a diversity of resources for studying genome plasticity and its regulation. Here, we sequenced and analyzed the macronuclear genome of different strains of Paramecium bursaria, a highly divergent species of the genus Paramecium which can stably establish endosymbioses with green algae. Results We assembled a high-quality macronuclear genome of P. bursaria and further refined genome annotation by comparing population genomic data. We identified several species-specific expansions in protein families and gene lineages that are potentially associated with endosymbiosis. Moreover, we observed an intensive chromosome breakage pattern that occurred during or shortly after sexual reproduction and contributed to highly variable gene dosage throughout the genome. However, patterns of copy number variation were highly correlated among genetically divergent strains, suggesting that copy number is adjusted by some regulatory mechanisms or natural selection. Further analysis showed that genes with low copy number variation among populations tended to function in basic cellular pathways, whereas highly variable genes were enriched in environmental response pathways. Conclusions We report programmed DNA rearrangements in the P. bursaria macronuclear genome that allow cells to adjust gene copy number globally according to individual gene functions. Our results suggest that large-scale gene copy number variation may represent an ancient mechanism for cells to adapt to different environments.

Download Full-text

Stimulation of adaptive gene amplification by origin firing under replication fork constraint

10.1101/2021.03.04.433911 ◽

2021 ◽

Author(s):

Alex J Whale ◽

Michelle King ◽

Ryan M Hull ◽

Felix Krueger ◽

Jonathan Houseley

Keyword(s):

Copy Number Variation ◽

Gene Amplification ◽

Copy Number ◽

Replication Fork ◽

Copper Resistance ◽

Template Switching ◽

Adaptive Mutations ◽

Number Variation ◽

H3k56 Acetylation ◽

Break Induced Replication

Adaptive mutations can cause drug resistance in cancers and pathogens, and increase the tolerance of agricultural pests and diseases to chemical treatment. When and how adaptive mutations form is often hard to discern, but we have shown that adaptive copy number amplification of the copper resistance gene CUP1 occurs in response to environmental copper due to CUP1 transcriptional activation. Here we dissect the mechanism by which CUP1 transcription in budding yeast stimulates copy number variation (CNV). We show that transcriptionally stimulated CNV requires TREX-2 and Mediator, such that cells lacking TREX-2 or Mediator respond normally to copper but cannot acquire increased resistance. Mediator and TREX-2 cause replication stress by tethering transcribed loci to nuclear pores, a process known as gene gating, and transcription at the CUP1 locus causes a TREX-2-dependent accumulation of replication forks indicative of replication fork stalling. TREX-2-dependent CUP1 gene amplification occurs by a Rad52 and Rad51-mediated homologous recombination mechanism that is enhanced by histone H3K56 acetylation and repressed by Pol32, factors known to alter the frequency of template switching during break induced replication (BIR). CUP1 amplification is also critically dependent on late firing replication origins present in the CUP1 repeats, and mutations that remove or inactivate these origins strongly suppress the acquisition of copper resistance. We propose that replicative stress imposed by nuclear pore association causes replication bubbles from these origins to collapse soon after firing, leaving an epigenetic scar of H3K56 acetylation that promotes template switching during later break induced replication events. The capacity for inefficient replication origins to promote copy number variation renders certain genomic regions more fragile than others, and therefore more likely to undergo adaptive evolution through de novo gene amplification.

Download Full-text