Inheriting an extra chromosome can sometimes be disastrous, but in the September issue of G3, Linder et al. investigate a chromosome duplication that helps yeast survive harsh conditions. Yeast with an extra copy of chromosome IV better tolerate hydrogen peroxide exposure, largely thanks to an extra copy of a gene that detoxifies the chemical. This work shows how large spontaneous mutations can help organisms thrive in the absence of natural genetic variation.

To generate mutants tolerant of hydrogen peroxide, the researchers plated haploid yeast (which have one copy of each chromosome) from three different strains on agar dosed with hydrogen peroxide. They chose thirty-seven colonies that tolerated higher concentrations of peroxide than their parent strains. Whole genome sequencing of those tolerant colonies revealed nearly half of them carried a duplication of chromosome IV, making it the most common mutation overall.

One colony had a duplication of the right arm of chromosome IV, allowing researchers to limit their search for the beneficial genes to just this area. They further narrowed down the search by systematically deleting portions of the right arm of the chromosome. Eventually, they targeted a region containing only five genes. Knocking them out one by one revealed most of these colonies’ resistance to hydrogen peroxide was due to an extra copy of the peroxidase gene TSA2, which is an enzyme that detoxifies peroxide. Boosting levels of TSA2 in parental cells increased their hydrogen peroxide tolerance, though not as much as the mutants carrying the whole duplicate chromosome. This means other unidentified factors on chromosome IV must also contribute to the phenotype.

This research shows chromosome duplication can be beneficial rather than harmful when the dosage of critical genes is increased. It all depends on the environment; in normal conditions, the hydrogen peroxide resistant mutants grew more slowly than their progenitors. Other studies in yeast have shown similar results for different stressors, suggesting spontaneous chromosome duplication may be commonly used by these microbes to quickly bridge the survival gap in tough environments.

CITATION

The Stress-Inducible Peroxidase TSA2 Underlies a Conditionally Beneficial Chromosomal Duplication in Saccharomyces cerevisiae

Robert A. Linder, John P. Greco, Fabian Seidl, Takeshi Matsui and Ian M. Ehrenreich

G3: Genes, Genomes, Genetics September 2017 7: 3177-3184;

https://doi.org/10.1534/g3.117.300069

http://www.g3journal.org/content/7/9/3177

If you’ve ever watched a procedural crime-solving show on television, you’re sure to have seen a lab tech magically produce results from a complicated assay in mere minutes. If you’re a wet lab scientist, you’ve probably found yourself wishing that “CSI technology” were real so you didn’t have to spend your whole day running PCRs and gels.

In this month’s issue of GENETICS, Wei and Williams, from the Montefiore Medial Center at the Albert Einstein College of Medicine, use sequencing technology that seems akin to science fiction to rapidly detect aneuploidy in just hours – an advance that could greatly improve the current state of clinical sequencing.

The study features the minION – a nanopore-based sequencer that reads and records DNA sequence in real time from very long reads. The minION sequencer is small – not much bigger than a USB thumb drive – and plugs directly into the computer that will be used to analyze the data. Inside the sequencer, nanopores create channels for DNA or other molecules to pass through a membrane that has an electric potential. When molecules pass through the nanopores, they disrupt the potential in a characteristic manner, which gives a known pattern in the read-out that lets them be identified. (Oxford Nanopore Technologies has an excellent animation explaining the technology in detail here.)

Wei and Williams developed a sample preparation and data-analysis method that uses the minION sequencer to produce rapid, real-time sequencing of short pieces of DNA, a change from the extremely long reads originally used in nanopore sequencing. Their methodology allowed them to detect aneuploidy, including trisomies and sex-chromosome abnormalities, in prenatal and miscarriage samples in less than four hours.

This methodology could potentially allow clinicians to detect aneuploidy in time-sensitive samples in just a few hours, for less than a thousand dollars – something that could only have been dreamt of even a decade ago. With exciting new methodologies, science fiction is on its way to science fact, and it’s picking up speed all the time.

CITATION

Wei S., Williams Z. 2016. Rapid Short-Read Sequencing and Aneuploidy Detection Using MinION Nanopore Technology. GENETICS, 202(1):37-44. doi: 10.1534/genetics.115.182311 http://www.genetics.org/content/202/1/37