HOTSPOT

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The most dramatic of mutations: whole genome duplication Whole genome duplication is an important force in evolution, and while it can help to enhance the adaptability of a lineage, there are serious biological challenges in dealing with twice as many chromosomes. We spoke to Dr Levi Yant about his work investigating how different organisms adapt to having a doubled genome complement An organism with more than two complete sets of chromosomes is known as a polyploid, and while this occurs throughout the eukaryotic kingdom, it is particularly prevalent in plants. Currently based at the John Innes centre in Norwich, UK, Dr Levi Yant is the Principal Investigator of an ERC-funded project investigating the impact of whole genome duplication (WGD), the process that gives rise to polyploidy. “There are serious implications around dealing with twice as many chromosomes, as it means there are twice as many opportunities for novel associations in the nucleus,” he outlines. The focus of the ERC project is on understanding how different organisms can adapt to having a doubled genome complement, despite attendant challenges. “Understanding how a lineage with a doubled genome can deal with some of the associated challenges is a broadly interesting topic, because this impacts adaptability of a species across kingdoms, from crop domestication to polyploid cancer lineages in humans,” says Dr Yant.

interest in the project is meiotic crossovers, which are important for stabilising the segregation of chromosomes. “One crossover between homologous chromosomes is necessary to stabilise meiosis, while there’s also the benefit that this cross-over reassorts genetic material,” he explains. “So, half a chromosome from the mother is switched to be associated with half a chromosome from the father.” Arabidopsis arenosa, a major model of adaptation to genome duplication. Photo credit: Filip Kolář

Repeatability of Evolution

Meiotic crossovers This research builds on the observation that meiosis, a type of cell division, is not a straightforward process in some of these young, genome-doubled lineages. This is largely because there are simply too many opportunities for association between similar chromosomes. “Instead of having just one possible partner - a homologue - suddenly there are three other possible partners, because of the doubling of the genome,” outlines Dr Yant. A major area of

environment. “There’s a lot of risk initially, as when the genome has these interactions, too many crossovers and entanglements can lead to chromosome breakage,” explains Dr Yant. “However, if you’re able to tweak meiosis early on, you then suddenly have twice as many chromosomes to play with, and that almost certainly increases the adaptability of the lineage. This has been shown rigorously for example in yeast, where groups have been able to take haploid, diploid and tetraploid genomes, and show that more chromosome copies can enhance evolutionary potential in experimental evolution studies in vitro.”

A greater number of meioitic cross-overs means that there is a greater diversity of genetic combinations in the population, which is a positive point in evolutionary terms. Genome doubling can be thought of as a high-risk, high-gain strategy, in terms of a population’s ability to adapt to the

The main focus of attention in the ERC project is on looking at the repeatability of the striking adaptations which have been found in independent lineages. A key part of this work centres around a large-scale comparative genomics and population genomics study on different, independently-derived polyploid plant and amphibian species. “We’re looking to understand the evolutionary changes in each of these species, and how repeatable these changes are,” outlines Dr Yant. By resequencing many individual diploids, and closely related tetraploids, Dr Yant and his colleagues have been able to observe the footprints of selection on the genome following genome duplication. “We’ve resequenced hundreds of genomes in the last three years, using large scale population genomic studies that now are beginning to present clear candidate genetic changes that allowed the stabilisation of meiosis in these

Meiosis-specific proteins ZYP1 (red) and ASY1 (green) juxtaposed between the chromatin loops (blue) during meiosis in Arabidopsis arenosa. Homologous chromosomes have paired and recombined, which is essential for normal levels of genetic crossovers as well as promoting correct segregation of chromosomes during sexual reproduction. We discovered ZYP1 and ASY1 evolving rapidly in response to genome duplication (polyploidy). Credit: James Higgins

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tetraploid plant and animal species,” he says. A diverse range of techniques are being applied in this project, including genetic, genomic and cytological approaches, to gain deeper insights into how different species adapted to the challenges associated with whole genome duplication. This work has yielded some interesting findings so far. “The first striking result was that the number of crossovers in meiosis was indeed successfully reduced in young tetraploids,” says Dr Yant. Now, by analysing the genes involved in this adaptation, researchers are looking to identify hotspots for genome evolution

they also suffer from some problems during meiosis similar to those which naturally adapted tetraploids have overcome,” explains Dr Yant. More broadly, this research could inform approaches to synthetic biology and rational crop improvement, helping to enhance crop resilience. “Some specific challenges linked to chromosome stabilisation include the ability to adapt to temperature volatility – which of course is also a very important problem for crops,” says Dr Yant. The main focus of attention in the project was on investigating the repeatability of adaption mechanisms to WGD, yet Dr Yant

If you’re able to tweak meiosis early on, you then suddenly have twice as many chromosomes to play with, and that increases the adaptability of the lineage across different genomes. “There appear to be functional hotspots – that is, it appears these adaptations are functionally constrained: the pathway and the output is the same, but fascinatingly, the way the genome does it differs in each case,” continues Dr Yant. “So there is a flexibility and innovation in each case: there are different ways in which genomes can come up with solutions to the same chromosomal challenge.”

Functional changes The longer-term goal in this research is to build a deeper mechanistic understanding of the functional changes in each of these cases and derive more general principles. This work also holds wider relevance in terms of our understanding of crop domestication. “Crops are typically polyploid, so they have double genomes. So, lots of things that we’ve been working on are relevant directly to crops, and

and his colleagues have also been able to explore other topics of interest. This includes research into some of the positive aspects of being genome-doubled. “Some of these polyploid species have been able to colonise really difficult, extremophile environments, such as toxic mines. We’ve found that tetraploids are able to deal with toxic mine sites where there’s a lot of lead and cadmium and low nutrient availability – for example, low levels of nitrogen and phosphorus,” outlines Dr Yant. This kind of situation, where plants have been able to colonise a seemingly unpromising environment, is highly interesting from an evolutionary genetics perspective. “In evolution there’s an initial challenge, and we understand the genes that mediate that. That then feeds into an adaptability – we aim to understand the genetic correlates of that, and we’re able to describe it using high-resolution, dense population genomics,” says Dr Yant.

HOTSPOT The population genomics of adaptation Project Objectives

This programme aims to understand evolutionary repeatability and constraint in the context of adaptation to whole genome duplication, an prevalent force in evolution and a driver of evolutionary diversification. This will provide insight into how organisms adapt to altered cellular environments and how conserved fundamental biochemical process, such as meiosis, evolve nimbly when required.

Project Funding

Major collaborators include Kirsten Bomblies (JIC also: http://bomblies.jic.ac.uk/). Funding is provided by a Starting Grant from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 679056).

Project Partners

• Cambridge University, UK • Charles University, Prague, CZ • Harvard University, USA • Stirling University UK • University of Nottingham UK • University of Leicester UK

Contact Details

Levi Yant, Project Leader John Innes Centre Norwich Research Park Colney Lane Norwich NR4 7UH United Kingdom T: +44 1603 450 000 E: levi.yant@jic.ac.uk W: http://yant.jic.ac.uk/ Levi Yant Levi Yant is a Project Leader in Cell and Developmental Biology at the John Innes Centre in Norwich, U.K. His work focuses on wild plant populations to learn how evolution finds solutions to significant environmental and physiological challenges. Among these are adaptations to high metal soils with low nutrients as well as the internal struggle in the nucleus following whole genome duplication. Using population genomic approaches, this work identifies changes specific to adapted populations, revealing candidate genes and process mediating adaptation. A major goal of his work is define which evolutionary routes are constrained and predictable, and which meander along diverse paths. This promises a view into rules broadly underlying evolutionary change. Dr Yant is currently moving his research programme to The University Nottingham as an Associate Professor of Evolutionary Genomics in the School of Life Sciences and University Beacon for Future Foods.

A cell following genome duplication. Blue is DNA and red is ZYP1, a protein we discovered to be undergoing adaptive evolution to help stabilise meiotic crossovers following genome duplication. Image: Chris Morgan

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