Evolutionary pathways to SARS-CoV-2 resistance are opened and closed by epistasis acting on ACE2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects a broader range of mammalian species than previously predicted, binding a diversity of angiotensin converting enzyme 2 (ACE2) orthologs despite extensive sequence divergence. Within this sequence degeneracy, we identify a rare sequence combination capable of conferring SARS-CoV-2 resistance. We demonstrate that this sequence was likely unattainable during human evolution due to deleterious effects on ACE2 carboxypeptidase activity, which has vasodilatory and cardioprotective functions in vivo. Across the 25 ACE2 sites implicated in viral binding, we identify 6 amino acid substitutions unique to mouse—one of the only known mammalian species immune to SARS-CoV-2. Substituting human variants at these positions is sufficient to confer binding of the SARS-CoV-2 S protein to mouse ACE2, facilitating cellular infection. Conversely, substituting mouse variants into either human or dog ACE2 abolishes viral binding, diminishing cellular infection. However, these same substitutions decrease human ACE2 activity by 50% and are predicted as pathogenic, consistent with the extreme rarity of human polymorphisms at these sites. This trade-off can be avoided, however, depending on genetic background; if substituted simultaneously, these same mutations have no deleterious effect on dog ACE2 nor that of the rodent ancestor estimated to exist 70 million years ago. This genetic contingency (epistasis) may have therefore opened the road to resistance for some species, while making humans susceptible to viruses that use these ACE2 surfaces for binding, as does SARS-CoV-2.

Evolutionary pathways in soil-landscape evolution models

Soils and landscapes can show complex, non-linear evolution, especially under changing climate or land use. Soil-landscape evolution models (SLEMs) are increasingly equipped to simulate the development of soils and landscapes over long timescales under these changing drivers, but provide large data output that can be difficult to interpret and communicate. New tools are required to analyse and communicate large model output. In this work, I show how spatial and temporal trends in previously published model results can be summarized and conceptualized with evolutionary pathways, which are possible trajectories of the development of soil patterns. Simulated differences in rainfall and land use control progressive or regressive soil development and convergence or divergence of the soil pattern. These changes are illustrated with real-world examples of soil development and soil complexity. The use of evolutionary pathways for analysing the results of SLEMs is not limited to the examples in this paper, but they can be used on a wide variety of soil properties, soil pattern statistics and models. With that, evolutionary pathways provide a promising tool to analyse and communicate soil model output, not only for studying past changes in soils, but also for evaluating future spatial and temporal effects of soil management practices in the context of sustainability.

Macroevolutionary Changes of Plants on Islands

<p>Insularity is known to produce predictable evolutionary changes in plants. For example, herbaceous plants often evolve woodiness and seeds tend to have reduced dispersal capabilities on islands. However, our understanding of how other plant traits may evolve on islands is lacking. Furthermore, plants are modular organisms and by investigating evolutionary changes in specific plant traits we may better understand macroevolutionary processes on islands. In this thesis, I investigate evolutionary changes in a range of plant traits on islands. First, I tested for evolutionary changes in seed size on islands (Chapter 2). Island plants consistently produced larger seeds than mainland relatives. Furthermore, this result was consistent regardless of differences in dispersal mode, growth form and evolutionary history. Selection may favour increased seed size to reduce dispersal distances. Additionally, selection may favour larger seeds due to the competitive advantage conferred to developing seedlings. Many animal taxa exhibit increased sexual size dimorphism (SSD) on islands, as predicted by the niche variation hypothesis. However, patterns of SSD among dioecious plants on islands are unknown. In Chapter 3 I tested for differences in SSD of dioecious plants that colonized four island groups from New Zealand (mainland). The degree of SSD did not vary predictable between island and mainland plants, contrary to predictions of the niche variation hypothesis. However, SSD was consistently female biased on the mainland and results suggest selection is acting to increase the size of both sexes on islands. Evolutionary changes in island plants may be a response to herbivory by unique large browsers. For example, the divaricate growth form is common in the New Zealand flora and may have deterred browsing moa. In Chapter 4 I tested for differences in traits associated with the divaricate growth form between plants from mainland New Zealand and Chatham Island. Results suggest that an absence of moa on Chatham Island has relaxed selection for traits associated with the divaricate growth form. An emerging body of research suggests aposematism (warning signals to herbivores) may be common in plants. However, previous investigations have not appreciated the fact that the perspective of terrestrial herbivores changes as plants grown vertically. Furthermore, ontogenetic changes in the capacity of plants to defend themselves may influence the reliability of warning signals. In Chapter 5 I tested for ontogenetic changes in two potentially aposematic signals produced by Pseudopanax crassifolius. Aposematism on upper leaf surfaces peaked early in ontogeny, providing a dishonest signal of defense. Conversely, signaling on the underside of leaves peaked later in ontogeny and scaled positively with structural defenses. The results of this thesis suggest selection is acting on specific plant traits on islands. Evolutionary pathways, such as the evolution of woodiness, may be better explained by considering selection acting on other plant traits. For example, selection acting on seed size may facilitate evolutionary size changes evident at later life-history stages. A lack of consensus exists regarding the role of insular herbivores in the evolution of island plants. The results of Chapters 4 and 5 suggest herbivory has played an important role in the evolution of novel morphology of island plants. Considering trait specific changes of plants on islands may further our understanding of prominent evolutionary pathways by pinpointing the action of selection.</p>

Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis

Neisseria meningitidis , the meningococcus, resides exclusively in humans and causes invasive meningococcal disease (IMD). The population of N. meningitidis is structured into stable clonal complexes by limited horizontal recombination in this naturally transformable species. N. meningitidis is an opportunistic pathogen, with some clonal complexes, such as cc53, effectively acting as commensal colonizers, while other genetic lineages, such as cc11, are rarely colonizers but are over-represented in IMD and are termed hypervirulent. This study examined theoretical evolutionary pathways for pathogenic and commensal lineages by examining the prevalence of horizontally acquired genomic islands (GIs) and loss-of-function (LOF) mutations. Using a collection of 4850 genomes from the BIGSdb database, we identified 82 GIs in the pan-genome of 11 lineages (10 hypervirulent and one commensal lineage). A new computational tool, Phaser, was used to identify frameshift mutations, which were examined for statistically significant association with genetic lineage. Phaser identified a total of 144 frameshift loci of which 105 were shown to have a statistically significant non-random distribution in phase status. The 82 GIs, but not the LOF loci, were associated with genetic lineage and invasiveness using the disease carriage ratio metric. These observations have been integrated into a new model that infers the early events of the evolution of the human adapted meningococcus. These pathways are enriched for GIs that are involved in modulating attachment to the host, growth rate, iron uptake and toxin expression which are proposed to increase competition within the meningococcal population for the limited environmental niche of the human nasopharynx. We surmise that competition for the host mucosal surface with the nasopharyngeal microbiome has led to the selection of isolates with traits that enable access to cell types (non-phagocytic and phagocytic) in the submucosal tissues leading to an increased risk for IMD.

Survivable hypothermia or torpor in a wild-living rat: rare insights broaden our understanding of endothermic physiology

Maintaining a high and stable body temperature as observed in endothermic mammals and birds is energetically costly. Thus, it is not surprising that we discover more and more heterothermic species that can reduce their energetic needs during energetic bottlenecks through the use of torpor. However, not all heterothermic animals use torpor on a regular basis. Torpor may also be important to an individual’s probability of survival, and hence fitness, when used infrequently. We here report the observation of a single, ~ 5.5 h long hypothermic bout with a decrease in body temperature by 12 °C in the native Australian bush rat (Rattus fuscipes). Our data suggest that bush rats are able to rewarm from a body temperature of 24 °C, albeit with a rewarming rate lower than that expected on the basis of their body mass. Heterothermy, i.e. the ability to withstand and overcome periods of reduced body temperature, is assumed to be an evolutionarily ancestral (plesiomorphic) trait. We thus argue that such rare hypothermic events in species that otherwise appear to be strictly homeothermic could be heterothermic rudiments, i.e. a less derived form of torpor with limited capacity for rewarming. Importantly, observations of rare and extreme thermoregulatory responses by wild animals are more likely to be discovered with long-term data sets and may not only provide valuable insight about the physiological capability of a population, but can also help us to understand the constraints and evolutionary pathways of different phenologies.