Massive amplification of genes is a desperate strategy taken by stressed populations adapting to an environment that has become inhospitable. Such amplifications can give an underperforming gene a much-needed boost in productivity simply by increasing its copy number. But counterintuitively, research reported in the May issue of G3 implies these amplifications may arise even in the absence of selective pressure and more frequently than expected.
The discovery was made in haploid Saccharomyces cerevisiae that the researchers weakened by replacing a critical tRNA synthetase gene with a version from a distant relative. This made the yeast replicate sluggishly until, after several generations, a few cells recovered their former vigor. These rejuvenated yeast must have adapted to using the foreign gene—but how? The researchers noticed that some of the revertants possessed enormous, grossly extended variants of chromosome VIII along with a slightly altered, but almost normal-sized copy.
Despite the hazards of major chromosomal rearrangements like these, the revertants thrived. In fact, they used the chromosomal catastrophe to their advantage. The enlarged chromosome VIII was formed by a large-scale amplification of the segment containing the tRNA synthetase gene. Along with the whole-chromosome duplication, this expansion increased the gene’s copy number three- to five-fold—enough to compensate for the suboptimal performance of the tRNA synthetase. As a side-effect, all the other genes in the same segment also increased in copy number by the same amount—except one. Seventy kilobases upstream of the tRNA synthetase, the CUP1 locus was copied an astonishing 800 times.
Strangely, CUP1 isn’t involved with tRNA synthesis. It encodes a metallothionein, a protein that increases resistance to copper salts. Amplification of CUP1 has been observed in the lab, but only in yeast subjected to stress-inducing concentrations of copper salts, which the researchers didn’t include. Even more bizarrely, the amplification in this experiment was more than ten times greater than typically seen in copper-exposed yeast.
To determine how this amplification occurred, the researchers analyzed the early subclones that gave rise to each revertant. They found that chromosome doubling and large-scale amplification of a segment of chromosome VIII could rescue the slow-growth phenotype, and these changes always preceded the increase in CUP1 copy number. The researchers propose that the initial large-scale chromosomal amplification that saved the yeast by increasing the copy number of the tRNA synthetase gene also happened to disrupt the nearby CUP1 locus, inadvertently creating a quasi-palindromic repeat.
There was little sequence homology among the quasi-palindromic repeats in each strain, leading the researchers to believe that each of these junctions was generated by a replication fork reversal that mistakenly joined lagging and leading strands. The fact that every expanded locus contained a single, unique quasi-palindromic unit while the CUP1 number varied suggests that that the CUP1 repeats arose as a chance consequence of the larger-scale amplification, possibly due to interference between neighboring replication bubbles. This mechanism explains how some cells ended up with many copies of CUP1—in one case, almost three orders of magnitude more than normal—even though there was no specific selective pressure acting on CUP1 copy number.
Interestingly, the authors report that the 1002 Yeast Genomes project has also identified natural yeast strains with large CUP1 copy numbers, some of which approach the scale reported in this study. This implies that the group’s findings aren’t merely a curiosity restricted to some quirky lab yeast—the same mechanism may exist in the wild, and amplification without selection may be more common than we know.
CITATION
Thierry, A., Khanna, V., Dujon, B. (2016). Massive Amplification at an Unselected Locus Accompanies Complex Chromosomal Rearrangements in Yeast.
G3: Genes|Genomes|Genetics, 6(5), 1201–1215. DOI: 10.1534/g3.115.024547
Nicole Haloupek is a freelance science writer and a recent graduate of UC Berkeley's molecular and cell biology PhD program.
View all posts by Nicole Haloupek »Read more in
-
Early Career Leadership Spotlight: Julio Molina Pineda
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Julio Molina Pineda Policy and Advocacy University of Arkansas Research Interest My research interests focus on using model organisms to genetically dissect complex traits related to human disease. My…
-
Early Career Leadership Spotlight: Peiwei Chen
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Peiwei Chen Accessibility Subcommittee California Institute of Technology Research Interest Far from a harmonious place, the genome is a battleground, where every bit of DNA fights for inheritance and…
-
#Dros23 GSA Poster Award winners
We are pleased to announce the GSA Poster Award winners from the 64th Annual Drosophila Research Conference! Undergraduate and graduate student members of the GSA were eligible for the awards, and a hard-working team of postdocs volunteered their time as judges. Congratulations to all! Undergraduate Students 1st Place: Sofia Karter Lopez, University of Toronto “Rab11 mediates E-cadherin recycling during…
-
Congratulations to the Fall 2022 DeLill Nasser Awardees!
GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Fall 2022! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…
-
New editors join GENETICS, G3 editorial boards
Several new editors are joining the GSA Journals. We’re excited to welcome Ricardo Zayas to the GENETICS editorial board under the Molecular Genetics of Development section, and on the G3: Genes|Genomes|Genetics board, we welcome Polly Campbell, Kevin Vogel, Joe Parker, and Ricardo Mallarino. Ricardo Zayas Associate Editor Ricardo Zayas is a Professor of Biology at…
-
Worms and Flies Provide Key Clues to Medical Mystery
This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee. By the time Bertrand Might was six months old, it was clear something was amiss. His muscles weren’t developing normally; he was…
-
Congratulations to the 2023 Early Career Leadership Program Cohort!
The Genetics Society of America (GSA) is excited to announce the latest cohort of student, postdoc, and early-career research leaders joining the Early Career Leadership Program. Participants receive training and mentoring while serving on committees charged with understanding the needs, interests, concerns, and challenges of early career scientist members of the GSA. As part of…
-
GSA LOCI: Local Outreach Community Initiatives @ GSA Conferences
Highlights: Local Outreach Community Initiatives (LOCI): The Genetics Society of America is committed to supporting the communities of the host cities of our conferences. This new year, we are excited to reconnect with our GSA community in meaningful ways within and beyond our existing programming. The GSA membership has created a caring and supportive environment…
-
New members of the GSA Board of Directors: 2023–2025
We are pleased to announce the election of five new leaders to the GSA Board of Directors: 2023 Vice President/2024 President Mariana Wolfner Distinguished Professor of Molecular Biology and Genetics and Stephen H. Weiss Presidential Fellow My research has focused on the genes and pathways that mediate sexual development and reproduction, primarily in Drosophila. From…
-
Lance David Miller: Lighting Your Own Fire by Finding the Right Resources
By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…
-
Graça Almeida-Porada: The Importance of Communication in a Technologically Advancing World
By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…