The Genomics Journey
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The genomics journey DYGEVO Professor Bernard Dujon discusses his research on yeasts and the usefulness of this family as model organisms in cutting-edge genetic manipulation experiments With such hypotheses, detailed knowledge has indicate that structural genome alterations been gained about the effect of population (segmental duplications, inversions, segmental size. But yeasts are unicellular fungi adapted insertion and deletion, gene loss) occur much to phases of very rapid clonal expansion under more rapidly than anticipated by classical favourable conditions, intermingled with phases methods. They tend to create more genetic of massive cell death. A glass of beer contains variations on a limited timescale than the more yeast individuals than the world’s human classically considered changes based on population. This abundance allows us to work sequence evolution. In addition, structural on rare genetic events without having to wait genome alterations create an abrupt, stepwise very long periods of time. pattern of evolution instead of a seemingly continuous spectrum of variation, more in line For what reasons do unicellular eukaryotic with original Hugo de Vries principles proposed genomes often prefer clonal expansions back in 1909 than with neo-Darwinian ideas on over regular reproduction cycles? gradual, permanent optimisation of the fittest. Many organisms seem to favour clonal How can the flexibility of yeast genomes expansion over sexual reproduction as be exploited to increase cell fitness when soon as conditions are appropriate. During simple nucleotide changes have a low Could you provide some context to your the sunny season, some insects engage in probability of accomplishing such a task? current project examining yeast genome parthenogenesis, and many plants propagate diversity – DYGEVO? What are your clonally. But it is true that unicellular organisms Both mechanisms can, in principle, contribute main objectives? do employ clonal expansion widely. The to evolutionary changes, but we did not reasons are probably numerous. One of them is observe simple nucleotide changes in our I started sequencing DNA in 1978. Back then, that they have a hard time identifying cells of experiments. This is in agreement with the people were sequencing pieces of genes, not the same species. Therefore, if they participate now precisely established mutation rates in genomes! I was interested in the dynamics in genetic exchange, they cannot easily limit yeast. To obtain a sufficient number of single of genomes from my early years of research, those exchanges to their own species. nucleotide changes to expect that one would, and always applied the newest methods by chance, alter fitness would take a much to study these questions (what a change in Unicellular fungi are highly viable models larger number of generations. Changing gene three decades!). for laboratory experiments. What is your copy number is much more rapid. trial methodology and why you have The complete sequencing of the genome of chosen to examine the basic mechanism of Do you intend to continue your research on Saccharomyces cerevisiae back in 1996 was eukaryotic genome dynamics? eukaryotic unicellular models? regarded as a scientific milestone, and I was involved in this achievement. At that time, There are many advantages of yeasts for genetic My lab is ageing, like myself, but during the nearly all scientists were moving to what experimentations. They are eukaryotic cells and time left we will continue to work in parallel they called ‘post-genomics’. Very few like phylogenetically related to the animal world, on comparisons of as large a number of yeast myself were interested in exploring genome including ourselves. Any genetic manipulation species as possible to learn from nature, and diversity. The DYGEVO project emerged in this can be controlled with extreme precision by to simultaneously run experiments on our context – I have always been keen to explore complete resequencing of the entire genome. developed model systems to check hypotheses. unconventional routes. Over 85 per cent of the S. cerevisiae genes have been functionally characterised, offering an The general functional organisation of unparalleled wealth of information for genetic eukaryotic genomes indicates that common analysis. There are no ethical constraints (except mechanistic and evolutionary principles are keeping our genetically engineered yeasts shared. Yet unicellular eukaryotic genomes strictly within the laboratory). are largely diverse, with different origins. Could you explain the effects of population What role is played by eukaryotic genome size and modes of reproduction on aetiology? dynamics in the evolution of these unicellular organisms? Classical population genetics usually considers sexual populations, and in many cases assume Our present data, based on comparative that they are panmictic and at equilibrium. genomics of many distinct yeast species, WWW.RESEARCHMEDIA.EU 53 DYGEVO Insights from yeasts Yeast continues to be one of the most important model organisms in modern biology. Today, a group at the Institut Pasteur in Paris, France, is using yeast to conduct a trio of novel experiments designed to deepen our understanding of the eukaryotic genome and possibly even challenge the accepted model of speciation SINCE WATSON AND CRICK first described that over 100,000 published research papers Dujon and his colleagues to experimentally the structure of DNA, the field of genetics concern its biology. simulate genetic events which would be very has expanded exponentially. Today, scientists rare in a wild population. The challenge for the have sequenced the entire human genome, Despite the huge amount of attention it has Pasteur team is to then ascertain the abundance cloned animals and illustrated the fundamental received, Dujon is confident that yeast still and importance of these laboratory-simulated principles of molecular evolution. Alongside has information to reveal: “I believe that this behaviours in the real world. these milestones was one of the most important is a topic in which much has yet to be learned, feats in modern biology – the sequencing of the given the power of novel technologies”. With DYGEVO Saccharomyces cerevisiae genome in 1996, an the development of genomic techniques, achievement in which Professor Bernard Dujon scientists now have the ability to artificially Dujon has recently embarked upon a new project from the Institut Pasteur in Paris, France, was engineer yeast genomes. Dujon’s current work called DYGEVO consisting of three distinct heavily involved. utilises this ability to explore how the dynamics research objectives: to quantify the impact of of genomic change affect evolution and flexibility in the yeast genome on cell fitness Dujon, who began his biological career in the population dynamics. and survival; to analyse the function of the late 1960s, now heads the Yeasts Molecular Genetics Unit at the Institut and is Professor of TO CLONE OR NOT TO CLONE? Molecular Genetics both there and at Université Pierre et Marie Curie. Throughout his career, One of the most interesting behaviours observed Dujon has focused on some of the central in yeasts is the ability to switch between sexual questions of genetics and evolutionary biology. and clonal reproduction. This behaviour is not unique to yeasts – also being seen in other organisms such as aphids – but remains rare. THE BENEFITS OF YEAST Given the correct environmental conditions, Yeast has been and continues to be one of yeast is capable of cloning itself, allowing one the most important experimental subjects in cell to form the basis of an entire colony. biology – it is a unicellular eukaryote capable of rapid population expansion, fits of evolutionary In many species, this type of reproduction change and subsequent adaptation: would render a population genetically ‘poor’ “Theoretically, a single yeast cell placed under and extremely susceptible to environmental favourable conditions would be able to produce, change, but not yeast: “Yeasts have developed Colonies of yeast cells with normal (large) and in a week, a clonal progeny capable of covering mechanisms to produce diversified populations genetically altered (small) genomes after incubation the globe with a crust several kilometres thick,” even after clonal expansion from a unique cell,” on a rich medium. Size difference illustrates the severe highlights Dujon. These characteristics have explains Dujon. This ability to undergo self- growth rate reduction due to controlled genetic made yeast such a popular model organism motivated genetic diversification has inspired alterations used for experiments. Yeast has been and continues to be one of the most important experimental subjects in biology – it is a unicellular eukaryote capable of rapid population expansion, fits of evolutionary change and subsequent adaptation 54 INTERNATIONAL INNOVATION BEYOND SACCHAROMYCETACEAE INTELLIGENCE Almost half of all sequenced yeast species today DYNAMICS AND EVOLUTION OF THE GENOMES OF YEAST, UNICELLULAR belong to the Saccharomycetaceae family, EUKARYOTIC MODELS meaning their genomes share a common global architecture with that of S. cerevisiae. Not only OBJECTIVES attractive for fermenting alcohol and leavening To combine the power of yeast genetics with bread, S. cerevisiae is also extremely well-suited new results from comparative genomics for experimental studies. to study the mechanisms underlying Flocculating yeast cells obtained after experimental