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Teaser, summary, work performed and final results

Periodic Reporting for period 3 - SpoKiGen (Spore killer genomics: elucidating causes and consequences of a fungal meiotic drive element)

Teaser

Summary

The principle of natural selection implies that any entity in nature that exhibits variation, reproduction and heritability may evolve. Hence, although Darwin (in 1859) framed his theory of evolution by natural selection around individuals within species, selection may act on other units of the biological hierarchy, such as genes, cells, organelles, species or even species groups. Conflict arises when natural selection favors a unit at one level, despite being harmful at another level. One example of this phenomenon is the intragenomic conflict resulting from natural selection favoring a genetic element, so that it spreads in a population despite being harmful to the individual carrying it. There is now a growing awareness that such conflicts are important motors for evolutionary change and innovation, and thus of crucial importance for all genetic form and function.

One class of selfish genetic elements is the meiotic drivers, also referred to as segregation distorters. These elements skew sexual transmission in their own favor, at the expense of other genes in the genome. Although meiotic drive is widespread in nature and has been identified in a wide range of eukaryotes, there is a profound lack of empirical insight into the evolutionary causes and consequences of this class of genetic element. This lack of knowledge is largely due to the difficulties in studying these elements and a lack of appropriate and tractable genetic models.
In this proposal, I introduce the ascomycete Neurospora as a novel system for the study of the evolutionary causes and consequences of meiotic drive. This sexual eukaryote model system is a carrier of the meiotic drive element Spore killer. The phenomenon of spore killing in Neurospora has been investigated for several decades, with research primarily focusing on its cytological properties and natural distribution. Data on the distribution of Spore killers in Neurospora suggest that it is an important driver of both genome evolution and higher-order processes such as speciation and mating-system transitions. Hence, the existing knowledge and resources of this system provide a foundation for the SpoKiGen research program, which combine experimental and state-of-the-art genomic approaches to I) identify and characterize the gene(s) encoding Spore killer elements, II) assess the strength of Spore killer as a meiotic driver, III) unravel the evolutionary history of the Spore killer complex in Neurospora, IV) investigate the association between Spore killer and genome evolution, and V) analyze the role of Spore killer as a driver of speciation and mating system transitions.
This SpoKiGen research program will make the Spore killer of Neurospora a primary and pioneering model for the study of selfish genetic elements and their effect on eukaryote genome evolution. Experimental and genomic results from the project will profoundly impact our understanding of the dynamics of segregation distorters as drivers of eukaryote genome evolution, as well as of higher-order macroevolutionary processes. Furthermore, the insights emerging from the project presented are conceptually important for basic evolutionary biology, in the study of natural selection acting a multitude of levels in a biological hierarchy. The concepts that will emerge from this project will be applicable to any project involving biological conflicts as such â€“ for example by increasing our understanding of what drives the progression of cancer tumors at the expense of the individual carrying it.

Work performed

We have achieved substantial progress towards reaching the main goal of the SpoKiGen project: i.e., to understand the causes and consequences of intragenomic conflict.

We have published one paper in which we address the consequences of intragenomic conflict in Neurospora. This study confirms conflict (or avoidance of such) as a driver of evolutionary change, and the suitability of the model system for addressing this issue:

â€¢ Meunier, C., Hosseini, S., Heidari, N., Maryush, Z., Johannesson, H. (2018). Multilevel selection in the filamentous ascomycete Neurospora tetrasperma. American Naturalist (in press): https://doi.org/10.1086/695803

Furthermore, as formulated in the general aims of the SpoKiGen project, we have generated a large genomic dataset of species and populations of fungi, focusing on the genus Neurospora but also included close relatives such as strains of Podospora, for comparative purposes. We have used that to create high quality assemblies from multiple strains, and to confirm how diversity is distributed in populations and species. Thereby, we have gotten far into building a platform for the study of meiotic drive elements in natural fungal populations and their consequences over evolutionary time. We describe the data gathering, the diversity and relationships in the three manuscripts described below.

We have used our generated dataset to identify the meiotic drive elements. Specifically, following the Aim I of the SpoKiGen project (â€œIdentification and characterization of the gene(s) encoding the Spore killer elementsâ€) we have used genomic data and genome-wise association, together with functional verification, to identify the Spore killer of N. sitophila, which was as of today not identified. The following manuscript --

â€¢ Manuscript 1. Jesper Svedberg, Aaron Vogan, Nicholas Rhoades, Dilini Sarmarajeewa, Thomas M. Hammond, David J. Jacobson, Martin Lascoux, Hanna Johannesson. A single gene causes meiotic drive in Neurospora sitophila.

-- is included in the PhD-thesis of Jesper Svedberg:

â€¢ PhD-thesis of Svedberg, J. Catching the Spore killers : Genomic conflict and genome evolution in Neurospora. Vol. 1651-6214 ; 1561 (Acta Universitatis Upsaliensis, 2017).

-- and is currently prepared for being submitted to a high impact scientific journal.

We are also for Aim I currently identifying yet unknown spore killers in the sister genus Podospora, for comparative purposes, and this study is yet ongoing and we plan to have a manuscript ready during the fall.

In our effort to asses the strength of the spore killers as meiotic drivers (Aim II of the SpoKiGen project), we have tried to create the introgressed lines with killer haplotypes in different genetic backgrounds. Due to incomplete recombination suppression in the spore killer haplotype of N. intermedia, the introgressions and subsequent fitness assays have turned out more problematic than we had anticipated. However, we hope to solve the problem by adapting the methodology, and will report the crossover frequencies in a manuscript:

â€¢ Manuscript 2. Jesper Svedberg, Sara Hosseini, Jun Chen, Iva Mozgova, Lars Hennig, Pennapa Manitchotpisit, Thomas M. Hammond, Martin Lascoux, Hanna Johannesson. The effect of genomic conflict on genome evolution in Neurospora intermedia

which is also included in the PhD-thesis of Jesper Svedberg and is planned to be submitted to a high-impact journal in the spring of 2018.

For Podospora, we have had better luck with the introgressions and are currently performing fitness assays to reveal the costs of carrying the spore killer genes in the fungal genomes.

Aim III of the project â€œDisentangling the evolutionary history of the Spore killer complex in Neurosporaâ€ has been fulfilled and is on its way to be published. We have used genomic data and phylogenetic analyses to confirm that within Neurospora, the three spore killers have evolved independently. It will be presented as parts of the two manuscr

Final results

So far, we have achieved very significant findings on causes of recombination suppression in Neuropora (Svedberg et al., Nat Comm), and the use of genomic and phylogenetic data has revealed multiple origin of spore killers over short evolutionary time, followed by concordant evolution of the accumulation of inversions and deleterious mutations in the spore-killer haplotypes. We anticipate that the SpoKiGen research program will make the Spore killer of Neurospora a primary and pioneering model for the study of selfish genetic elements and their effect on eukaryote genome evolution. Experimental and genomic results from the project will profoundly impact our understanding of the dynamics of segregation distorters as drivers of eukaryote genome evolution, as well as of higher-order macroevolutionary processes. Furthermore, the insights emerging from the project presented are conceptually important for basic evolutionary biology, in the study of natural selection acting a multitude of levels in a biological hierarchy. The concepts that will emerge from this project will be applicable to any project involving biological conflicts as such â€“ for example by increasing our understanding of what drives the progression of cancer tumors at the expense of the individual carrying it.