Dataset Information

Copy number variation is associated with gene expression change in archaea.

ABSTRACT: Genomic instability, although frequently deleterious, is also an important mechanism for microbial adaptation to environmental change. Although widely studied in bacteria, in archaea the effect of genomic instability on organism phenotypes and fitness remains unclear. Here we use DNA segmentation methods to detect and quantify genome-wide copy number variation (CNV) in large compendia of high-throughput datasets in a model archaeal species, Halobacterium salinarum. CNV hotspots were identified throughout the genome. Some hotspots were strongly associated with changes in gene expression, suggesting a mechanism for phenotypic innovation. In contrast, CNV hotspots in other genomic loci left expression unchanged, suggesting buffering of certain phenotypes. The correspondence of CNVs with gene expression was validated with strain- and condition-matched transcriptomics and DNA quantification experiments at specific loci. Significant correlation of CNV hotspot locations with the positions of known insertion sequence (IS) elements suggested a mechanism for generating genomic instability. Given the efficient recombination capabilities in H. salinarum despite stability at the single nucleotide level, these results suggest that genomic plasticity mediated by IS element activity can provide a source of phenotypic innovation in extreme environments.

SUBMITTER: Dulmage KA

PROVIDER: S-EPMC6202454 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Copy number variation is associated with gene expression change in archaea.

Dulmage Keely A KA Darnell Cynthia L CL Vreugdenhil Angie A Schmid Amy K AK

Microbial genomics 20180824 9

Genomic instability, although frequently deleterious, is also an important mechanism for microbial adaptation to environmental change. Although widely studied in bacteria, in archaea the effect of genomic instability on organism phenotypes and fitness remains unclear. Here we use DNA segmentation methods to detect and quantify genome-wide copy number variation (CNV) in large compendia of high-throughput datasets in a model archaeal species, Halobacterium salinarum. CNV hotspots were identified t ...[more]

PMID: 30142055

Similar Datasets

Project description:Copy number variation (CNV) is rife in eukaryotic genomes and has been implicated in many human disorders, particularly cancer, in which CNV promotes both tumorigenesis and chemotherapy resistance. CNVs are considered random mutations but often arise through replication defects; transcription can interfere with replication fork progression and stability, leading to increased mutation rates at highly transcribed loci. Here we investigate whether inducible promoters can stimulate CNV to yield reproducible, environment-specific genetic changes. We propose a general mechanism for environmentally-stimulated CNV and validate this mechanism for the emergence of copper resistance in budding yeast. By analysing a large cohort of individual cells, we directly demonstrate that CNV of the copper-resistance gene CUP1 is stimulated by environmental copper. CNV stimulation accelerates the formation of novel alleles conferring enhanced copper resistance, such that copper exposure actively drives adaptation to copper-rich environments. Furthermore, quantification of CNV in individual cells reveals remarkable allele selectivity in the rate at which specific environments stimulate CNV. We define the key mechanistic elements underlying this selectivity, demonstrating that CNV is regulated by both promoter activity and acetylation of histone H3 lysine 56 (H3K56ac) and that H3K56ac is required for CUP1 CNV and efficient copper adaptation. Stimulated CNV is not limited to high-copy CUP1 repeat arrays, as we find that H3K56ac also regulates CNV in 3 copy arrays of CUP1 or SFA1 genes. The impact of transcription on DNA damage is well understood, but our research reveals that this apparently problematic association forms a pathway by which mutations can be directed to particular loci in particular environments and furthermore that this mutagenic process can be regulated through histone acetylation. Stimulated CNV therefore represents an unanticipated and remarkably controllable pathway facilitating organismal adaptation to new environments.

Dataset Information

Copy number variation is associated with gene expression change in archaea.

Publications

Copy number variation is associated with gene expression change in archaea.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets