Gamete signalling underlies the evolution of mating types and their number

Predictions about the evolution of sex determination mechanisms have mainly focused on animals and plants, whereas unicellular eukaryotes such as fungi and ciliates have received little attention. Many taxa within the latter groups can stochastically switch their mating type identity during vegetative growth. Here, we investigate the hypothesis that mating type switching overcomes distortions in the distribution of mating types due to drift during asexual growth. Using a computational model, we show that smaller population size, longer vegetative periods and more mating types lead to greater distortions in the distribution of mating types. However, the impact of these parameters on optimal switching rates is not straightforward. We find that longer vegetative periods cause reductions and considerable fluctuations in the switching rate over time. Smaller population size increases the strength of selection for switching but has little impact on the switching rate itself. The number of mating types decreases switching rates when gametes can freely sample each other, but increases switching rates when there is selection for speedy mating. We discuss our results in light of empirical work and propose new experiments that could further our understanding of sexuality in isogamous eukaryotes

A new mechanism for spatial pattern formation via lateral and protrusion-mediated lateral signalling

Tissue organization and patterning are critical during development when genetically identical cells take on different fates. Lateral signalling plays an important role in this process by helping to generate self-organized spatial patterns in an otherwise uniform collection of cells. Recent data suggest that lateral signalling can be mediated both by junctional contacts between neighbouring cells and via cellular protrusions that allow non-neighbouring cells to interact with one another at a distance. However, it remains unclear precisely how signalling mediated by these distinct types of cell-cell contact can physically contribute to the generation of complex patterns without the assistance of diffusible morphogens or pre-patterns. To explore this question, in this work we develop a model of lateral signalling based on a single receptor/ligand pair as exemplified by Notch and Delta. We show that allowing the signalling kinetics to differ at junctional versus protrusion-mediated contacts, an assumption inspired by recent data which show that the cleavage of Notch in several systems requires both Delta binding and the application of mechanical force, permits individual cells to act to promote both lateral activation and lateral inhibition. Strikingly, under this model, in which Delta can sequester Notch, a variety of patterns resembling those typical of reaction-diffusion systems is observed, together with more unusual patterns that arise when we consider changes in signalling kinetics, and in the length and distribution of protrusions. Importantly, these patterns are self-organizing-so that local interactions drive tissue-scale patterning. Together, these data show that protrusions can, in principle, generate different types of patterns in addition to contributing to long-range signalling and to pattern refinement

Cell-cell signalling in sexual chemotaxis: a basis for gametic differentiation, mating types and sexes

While sex requires two parents, there is no obvious need for them to be differentiated into distinct mating types or sexes. Yet this is the predominate state of nature. Here, we argue that mating types could play a decisive role because they prevent the apparent inevitability of self-stimulation during sexual signalling. We rigorously assess this hypothesis by developing a model for signaller-detector dynamics based on chemical diffusion, chemotaxis and cell movement. Our model examines the conditions under which chemotaxis improves partner finding. Varying parameter values within ranges typical of protists and their environments, we show that simultaneous secretion and detection of a single chemoattractant can cause a multifold movement impediment and severely hinder mate finding. Mutually exclusive roles result in faster pair formation, even when cells conferring the same roles cannot pair up. This arrangement also allows the separate mating types to optimize their signalling or detecting roles, which is effectively impossible for cells that are both secretors and detectors. Our findings suggest that asymmetric roles in sexual chemotaxis (and possibly other forms of sexual signalling) are crucial, even without morphological differences, and may underlie the evolution of gametic differentiation among both mating types and sexes

Development Education in Theory and Practice: An Educator's Resource

Over the course of three years, the UNIDEV project sought to promote youth awareness and engagement with the MDG (Millennium Development Goals) and post-2015 frameworks in universities in Cyprus, Slovakia and Ireland. The partners undertook a range of activities as part of the programme. The idea for this resource arose out of a desire to develop specific development education materials that would target the new EU member state sector, and which would bring something new to the significant stock of development education resources already available. To this end, instead of providing just another book on general development education topics, the aim was to address contemporary development issues with a focus on the needs of educators in the new EU member states, as well as drawing material from contributors in those countries. The hope is that this book will be used by academics, researchers, NGO practitioners and students as part of development education work to further their understanding of key development issues facing the global community, and more so, to encourage citizen action to bring about a fairer more equitable world. The book covers twelve themes, each chapter includes both a conceptual overview and a teaching methodology section. The conceptual overview introduces the topic, explores the key concepts, theories and current debates. The teaching methodology section offers educators a set of tools that could help them introduce the topic in both formal and non-formal settings

Development Education in Theory and Practice: An Educator's Resource

Over the course of three years, the UNIDEV project sought to promote youth awareness and engagement with the MDG (Millennium Development Goals) and post-2015 frameworks in universities in Cyprus, Slovakia and Ireland. The partners undertook a range of activities as part of the programme. The idea for this resource arose out of a desire to develop specific development education materials that would target the new EU member state sector, and which would bring something new to the significant stock of development education resources already available. To this end, instead of providing just another book on general development education topics, the aim was to address contemporary development issues with a focus on the needs of educators in the new EU member states, as well as drawing material from contributors in those countries. The hope is that this book will be used by academics, researchers, NGO practitioners and students as part of development education work to further their understanding of key development issues facing the global community, and more so, to encourage citizen action to bring about a fairer more equitable world. The book covers twelve themes, each chapter includes both a conceptual overview and a teaching methodology section. The conceptual overview introduces the topic, explores the key concepts, theories and current debates. The teaching methodology section offers educators a set of tools that could help them introduce the topic in both formal and non-formal settings

Theoretical studies on the role and evolution of mating types and two sexes

Why there are two distinct sexes has received little attention compared with that lavished on the value of sexual reproduction. While sex requires two parents, there is no obvious need for these to be of different sexes. Furthermore, self-incompatible gametes seemingly reduce the likelihood of finding a partner. What causes mating types and sexes to predominate in nature remains a conundrum. The uniparental inheritance (UPI) of mitochondria (in which only one sex, usually the female, passes on its mitochondria) is widespread among sexual organisms. Theoretical work suggests that the evolution of two sexes can be understood in the light of mitochondrial inheritance. However, the exact role of UPI is not clearly understood. Part I of this thesis considers the evolution of self-incompatible mating types in relation to this perspective, using probability theory and population genetics. Chapter 2 studies the impact of UPI on interactions between genes in the mitochondria and the nucleus, in an effort to elucidate the role of UPI itself. In Chapter 3, I develop a new, explicit theoretical model that challenges the prominent view that selection for UPI leads to the establishment of self-incompatible mating types and sexes. An alternative hypothesis proposes that mating types evolved as a consequence of selection for asym- metry in gamete attraction and recognition. This idea is based on the assumption that an asymmetry in gamete communication leads to more effective attraction and recognition. In Part II of this thesis, I examine this idea further. In Chapter 4, I perform an extensive literature review of mating type interactions and provide empirical support for the prediction that an asymmetry in signalling is indeed common in nature. The underlying assumptions of this hypothesis are linked to the physical constraints that gametes experi- ence during sex, and the role of polarity in cell-cell interactions. To assess the impact of these constraints rigorously, in Chapter 5 I develop a biophysical model for signaller-detector dynamics based on chemical diffusion, chemotaxis and individual cell movement that can be tested in silico and in vitro. This thesis examines the role and origins of self-incompatible mating types and sexes. The novel theo- retical methods and perspective on the empirical literature presented here place this evolutionary question in a fresh context and encourage further theoretical and empirical work

Interpretable Alzheimer's Disease Classification Via a Contrastive Diffusion Autoencoder

In visual object classification, humans often justify their choices by comparing objects to prototypical examples within that class. We may therefore increase the interpretability of deep learning models by imbuing them with a similar style of reasoning. In this work, we apply this principle by classifying Alzheimer's Disease based on the similarity of images to training examples within the latent space. We use a contrastive loss combined with a diffusion autoencoder backbone, to produce a semantically meaningful latent space, such that neighbouring latents have similar image-level features. We achieve a classification accuracy comparable to black box approaches on a dataset of 2D MRI images, whilst producing human interpretable model explanations. Therefore, this work stands as a contribution to the pertinent development of accurate and interpretable deep learning within medical imaging

Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning

Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning

Mitochondrial Involvement in Vertebrate Speciation? The Case of Mito-nuclear Genetic Divergence in Chameleons

Compatibility between the nuclear (nDNA) and mitochondrial (mtDNA) genomes is important for organismal health. However, its significance for major evolutionary processes such as speciation is unclear, especially in vertebrates. We previously identified a sharp mtDNA-specific sequence divergence between morphologically indistinguishable chameleon populations (Chamaeleo chamaeleon recticrista) across an ancient Israeli marine barrier (Jezreel Valley). Because mtDNA introgression and gender-based dispersal were ruled out, we hypothesized that mtDNA spatial division was maintained by mito-nuclear functional compensation. Here, we studied RNA-seq generated from each of ten chameleons representing the north and south populations and identified candidate nonsynonymous substitutions (NSSs) matching the mtDNA spatial distribution. The most prominent NSS occurred in 14 nDNA-encoded mitochondrial proteins. Increased chameleon sample size (N = 70) confirmed the geographic differentiation in POLRMT, NDUFA5, ACO1, LYRM4, MARS2, and ACAD9. Structural and functionality evaluation of these NSSs revealed high functionality. Mathematical modeling suggested that this mito-nuclear spatial divergence is consistent with hybrid breakdown. We conclude that our presented evidence and mathematical model underline mito-nuclear interactions as a likely role player in incipient speciation in vertebrates

The evolution of mating type switching

This is the final version of the article. Available from Wiley via the DOI in this record.Predictions about the evolution of sex determination mechanisms have mainly focused on animals and plants, whereas unicellular eukaryotes such as fungi and ciliates have received little attention. Many taxa within the latter groups can stochastically switch their mating type identity during vegetative growth. Here, we investigate the hypothesis that mating type switching overcomes distortions in the distribution of mating types due to drift during asexual growth. Using a computational model, we show that smaller population size, longer vegetative periods and more mating types lead to greater distortions in the distribution of mating types. However, the impact of these parameters on optimal switching rates is not straightforward. We find that longer vegetative periods cause reductions and considerable fluctuations in the switching rate over time. Smaller population size increases the strength of selection for switching but has little impact on the switching rate itself. The number of mating types decreases switching rates when gametes can freely sample each other, but increases switching rates when there is selection for speedy mating. We discuss our results in light of empirical work and propose new experiments that could further our understanding of sexuality in isogamous eukaryotes.Z.H. was funded by an Engineering and Physical Sciences Research Council Doctoral Prize Fellowship (EP/L504889/1) and A.P. by grants from the Engineering and Physical Sciences Research Council (EP/F500351/1, EP/I017909/1, EP/K038656/1). BK was supported by a 2020 Science Research Fellowship (EP/I017909/1) and an Early Career Fellowship from the Leverhulme Trust (ECF-2015-273)