Barbara McClintock deserves to be a household name, yet she remains relatively unknown. She was a pioneering maize geneticist who received the Nobel Prize in Physiology or Medicine, an honor rarely bestowed upon her plant biologist peers. Her ground-breaking discovery of “jumping genes” was truly revolutionary. Years later, the scientific community continues to unravel the significance of transposons across various organisms, including plants, animals, and fungi, demonstrating the profound impact of her work on our understanding of genetics and how life evolves.
The topic of transposons, the scientific term for McClintock’s jumping genes, was among the recurrent topics at #Fungal24 the 32nd Fungal Genetics Conference held in March 2024 at the Asilomar Conference Grounds in Pacific Grove, California. Approximately 850 scientists from 35 countries embarked on the biennial journey to the California coast for an intensive conference experience, featuring sessions that began at 9 a.m. and poster presentations extending past 10 p.m.
The location on the California Pacific Coast is breathtakingly stunning. Over the years, there have been tentative attempts to relocate the conference to manage increasing attendance. However, these efforts were unsuccessful as attendees are drawn to what was once called the “epicentre of happiness” by an enthusiastic participant, returning every other March to enjoy the conference’s beautiful setting and congenial atmosphere. Seasoned participants are well aware that early registration is crucial, as the event consistently reaches full capacity.
What if you had 10,000 fungal genomes?
Fungi have captured the public’s imagination. Whether it’s Merlin Sheldrake’s book “Entangled Life” and associated movie or their increasingly frequent appearances in popular culture, fungi seem to be everywhere these days. Their allure is undeniable; these organisms play crucial roles in ecosystems, breaking down organic matter and recycling nutrients, while also forming symbiotic relationships that are essential for plant growth. Fungi are also marvels of biological innovation, showcasing incredible diversity in form, function, and habitat. Whether they infect plants or animals, they can manipulate their hosts in incredibly sophisticated ways. Check the fungi that turn plants or ants into Zombies. Fungi also have fascinating life cycles and capabilities and their potential in biotechnology is vast, including applications in medicine, environmental clean-up, and sustainable materials.
At the genome level, we are finally tapping into the incredible diversity of fungi. Fungal genomes have been sequenced for over two decades, yet the field of fungal genomics appears to be undergoing a renaissance. As is common in biology, genuine insight stems from comparative analyses. The community now boasts an expanding collection of fungal genome sequences, with DOE Joint Genome Institute’s scientist Igor Grigoriev showcasing progress toward sequencing 10,000 fungal genomes. This field is also experiencing a second wind thanks to advancements in long-read genome sequencing technology, which provides nearly complete, if not complete, assemblies of the moderately sized fungal genomes. These advancements are unveiling new insights that were overlooked by earlier, first-generation genome sequencing efforts, offering a more comprehensive understanding of fungal biology and evolution.
Towards predicting fungal lifestyles from genomes
Artificial intelligence (AI) is currently a hot topic in biology, speeding up research, enhancing data analysis, and driving innovations in various sub-disciplines. In protein structure prediction, AI tools like AlphaFold are providing unprecedented insights into protein folding, crucial for understanding function. By leveraging the increasing availability of fungal genomic data, Richard Hamelin at the University of British Columbia, Vancouver, and his collaborators have showcased a proof-of-concept study using genomic signatures to predict the lifestyles and traits of fungal plant pathogens. They employed machine learning techniques to forecast lifestyles and traits across different taxonomic groups of plant pathogenic fungi, providing a method that complements phylogenetic analyses to support biosurveillance efforts in identifying new threats from pathogens.
The Comeback CHEF: uncovering the dark matter of fungal genomes
CHEF — the vinyl records of fungal genomics — is a classic method that is making a comeback. CHEF, standing for Clamped Homogeneous Electric Field, is a pulsed-field gel electrophoresis technique for separating large DNA molecules, including the smaller fungal chromosomes or mini-chromosomes. In addition, CHEF chromosome patterns can highlight structural variation that can be overlooked by genome sequencing methods, revealing the “dark matter” of fungal genomes. This year’s Asilomar conference revealed a resurgence of interest in pulsed-field gel electrophoresis methods, as a complement to long-read genome assemblies. Several presentations on genome biology prominently featured CHEF gels, illustrating their renewed relevance alongside analyses of genome sequence data, underscoring their role in delving deeper into structure-function relationships in fungal genomics.
Anna Selmecki from the University of Minnesota merges CHEF analyses with sequencing to explore the genomic diversity of human-pathogenic Candida yeast. Anna aptly remarked that CHEF gels provide an intuitive method for detecting and showcasing chromosomal variation and used the method alongside genome sequencing to demonstrate that resistance to the antifungal agent azole in Candida albicans is predominantly associated with structural variations and changes in gene copy number, rather than point mutations. Additionally, my fellow plant pathologist Reem Aboukhaddour from Agriculture and Agri-Food Canada, highlighted the enduring value of CHEF gel data, even decades old, for pinpointing the chromosomal locations of effector genes within the genome assemblies of the tan spot pathogen. Indeed, reliable data remains timeless and always in vogue.
At The Sainsbury Lab, we’ve employed CHEF techniques to delve into the chromosomal diversity of the blast fungus Magnaporthe oryzae. Thorsten Langner and Adeline Harant resurrected a dusty CHEF apparatus, which had lain dormant for over two decades, to conduct these classic experiments. Subsequently, Thorsten, joined by Cristina Barragan and collaborators, integrated this method with genome sequencing to probe clonal lineages of the rice blast fungus. Their findings revealed that the blast fungus harbors mini-chromosomes which are being transferred horizontally across different lineages of the pathogen. Both Thorsten, now at the Max Planck Institute for Biology in Tuebingen, and Cristina gave talks on the topic at the Conference. Cristina’s work was also detailed in a poster presented at the conference, which she has since shared on Zenodo for wider access.
In the midst of this resurgence, BioRad, the manufacturer of a widely used model of CHEF apparatus, has recently decided to discontinue their products. This is particularly disheartening for early career researchers who are establishing their laboratories and plan to utilize this methodology to investigate the chromosomal diversity and evolution of their favorite fungi. Hopefully, someone at BioRad might take note of this appeal and reconsider their decision, recognizing the significant impact their tools have on the scientific community.
To boldly jump: giant Starships shaping fungal genomes
Jumping genes, or transposons, serve as potent drivers of change within fungal genomes. By inserting themselves into various locations within the genome, affecting gene structure and expression and carrying cargo genes from one fungus to another, they drive genetic diversity and innovation. There is increasing evidence indicating that transposons are key players in the saga of fungal adaptation and evolution, pivotal for their success across diverse ecosystems. Barbara McClintock’s legacy lives on through fungal genomics.
Arguably, the most exciting discovery in fungal genomics of recent years are a family of large sized transposons that carry cute star wars inspired names such as Starship, Voyager, Sanctuary and Horizon. These belong to a class of cut-and-paste DNA transposable elements — Starships — that are abundant across fungal species and have shaped fungal genomes for millions of years. Emile Gluck-Thaler at University of Wisconsin, Madison, reported at the Conference that Starships make up to 4% of the Aspergillus fumigatus pangenome. You can check whether your favorite genome carries a Starship by using the tool STARFISH developed by Emile and collaborator Aaron Vogan at University of Uppsala.
Starships were only recently discovered, thanks to the era of long-read genome assemblies. Indeed, their substantial size — up to 400 kbp — caused them to be overlooked in the somewhat fragmented short-read genome assemblies. Now, with the advent of complete genome assemblies, they are popping up everywhere, shedding new light on previous observations.
This is precisely what Megan McDonald from the University of Birmingham has reported. In a new twist on an old classic, Megan found that the well-known virulence effector gene ToxA, previously identified as horizontally transferred between three wheat fungal pathogen species via a 14 kbp ToxhAT transposon, is actually part of a much larger ~200 kbp Starship family of transposons, named Sanctuary and Horizon. Megan demonstrated that these mobile genetic elements have facilitated the movement of ToxA, thereby conferring new virulence attributes upon the wheat pathogens
Fungal adaptation demons: when transposons go wild
University of Neuchâtel’s Daniel Croll provided further insight into how transposons contribute to fungal evolution. He reviewed the various ways transposons influence function, from the epigenetic regulation of virulence gene expression to impacts on genome size and structure. Daniel describes this dynamic as a “devil’s bargain” for fungal pathogens: while transposons can offer immediate advantages, they also pose long-term risks due to potential mutational meltdowns. A fascinating case study by Daniel, along with colleagues Alice Feurtey and Cécile Lorrain, revealed that the global dispersal of the wheat pathogen Zymoseptoria tritici coincided with a reduction in genomic defense against transposons, marked by the deactivation of the RIP (Repeat-Induced Point mutation) system. This relaxation likely accelerated the pace of adaptive mutations affecting virulence and fungicide resistance, illustrating the complex trade-offs inherent in transposon dynamics.
The future is here: experimental fungal genome evolution
With transposons like the giant Starships facilitating the movement of cargo genes across species, transporting hundreds of thousands of base pairs, brace for the forthcoming research phase aimed at elucidating the genetic mechanisms underpinning this horizontal gene transfer. Andrew Urquhart from Macquarie University in Australia has experimentally confirmed the transposition of Starship elements and pinpointed a tyrosine recombinase named Captain as the catalyst for their mobility. Additionally, through University of Cologne Yukiyo Sato’s presentation, we caught a glimpse of a new research field “experimental fungal genome evolution”, demonstrating how CRISPR/Cas gene editing can be employed to rigorously test hypotheses regarding genome evolution and the genetic components that drive structural variation. In the coming years, we can anticipate seeing analogous experiments to those of Yukiyo to establish causality and test hypotheses concerning transposons, mini-chromosomes, and other structural variation drivers within fungal genomes.
Addressing inequity in access to genomics
The Fungal Genetics Conference is organized by The Genetics Society of America, which commendably supports diversity and provides travel grants to students like Université de Montréal Bhagya C. Thimmappa. Such initiatives are vital, and it’s imperative for scientific societies to channel more funds back into the community, embodying the role of catalysts for positive change. Nonetheless, despite, for example, a sizeable contingent from far away South Africa, only 35 countries were represented at the Asilomar meeting, with a strong bias toward Western countries.
Genomics is blooming, again, but access to genome sequencing remains unequal across the globe. This is why James Canham and I have founded the non-profit GetGenome to empower scientists throughout the world by providing equitable access to genomics technology and genomics-related training and education. Our motto is Genomics for All. Although we are currently prioritizing bacterial genomes, stay tuned for fungal focused activities.
Acknowledgements
I’m grateful to Sebastian Schornack and many colleagues for their input and critical suggestions. The article was written with assistance from ChatGPT.
This article is available on a CC-BY license via Zenodo.
Cite as: Kamoun, S. (2024) Jumping genes and other fungal stories from Asilomar. Zenodo. https://doi.org/10.5281/zenodo.10829353
