Biology subjects

MacDonald, H.

Publications and source records attributed to MacDonald, H..

7 recordsLinked to original sources

bioRxiv2025

Parallel evolution of full-length genomes in a long-term evolution experiment with phage ΦX174

The study of evolution in organisms with high mutation rates requires detailed data on the genomic composition of the population. Here we report on an innovative use of high-throughput sequencing technology combined with rapid experimental evolution that allowed us to follow the genetic diversification of four independent bacteriophage populations that we evolved without actively imposing any selection pressures (in addition to those inherent in the bacterial cell environment) for 412 generations in unprecedented detail. Tracing over 80000 bacteriophage genomes, representing 884 distinct genotypes, we find that the patterns of viral diversification result in largely non-congruent genotype distributions, but also document multiple instances of parallel evolution. Unlike previous observations of parallelism in viral evolution, we do not just see the parallel evolution of mutations at single sites, but on the level of full-length genomes. Computer simulations that recapitulate our experiments in great detail show that this degree of parallelism is inconsistent with neutral evolution. We further show that the observed extent of parallel evolution biases phylodynamic analysis of migration rates, and wrongly estimates significant migration between the independent evolution lines. Our approach is applicable to many other viruses and paves the way to advanced population genetic investigations that aim to shed light on phenomena that relate to genetic linkage across the genome.

evolutionary biology↗

bioRxiv2021

Host phenology can select for multiple stable parasite virulence strategies

Host phenology is an important driver of parasite transmission dynamics and evolution. Prior research has demonstrated that host phenology can drive monocyclic, obligate-killer parasites to evolve an intermediate virulence strategy where all parasites kill their host just before the season ends to limit the death of parasite progeny in the environment. The impact of host seasonality on parasites that are not constrained to a monocyclic life-cycle, however, cannot be inferred from these results. Here we present a mathematical model that demonstrates that many, but not all, seasonal host activity patterns support multiple evolutionarily stable parasite strategies (ESS), although these strategies cannot coexist in the same system. The specific monocyclic and polycyclic parasite evolutionarily stable strategies in each phenological pattern are interspersed with less-fit mono- and polycyclic strategies (evolutionary repellors). The ESS that dominates each system at equilibrium is a function of the strategy of the parasite introduced into the system. The results demonstrate that host phenology can, in theory, maintain diverse parasite strategies among isolated geographic locations.

evolutionary biology↗

bioRxiv2021

How host phenology impacts multi-season epidemic cycles

Parasite-host interactions can result in periodic population dynamics when parasites over-exploit host populations. The timing of host seasonal activity, or host phenology, determines the frequency and demographic impact of parasite-host interactions which may govern if the parasite can sufficiently over-exploit their hosts to drive population cycles. We describe a mathematical model of a monocyclic, obligate-killer parasite system with seasonal host activity to investigate the consequences of host phenology on host-parasite dynamics. The results suggest that parasites can reach the densities necessary to destabilize host dynamics and drive cycling in only some phenological scenarios, such as environments with short seasons and synchronous host emergence. Further, only parasite lineages that are sufficiently adapted to phenological scenarios with short seasons and synchronous host emergence can achieve the densities necessary to over-exploit hosts and produce population cycles. Host-parasite cycles can also generate an eco-evolutionary feedback that slows parasite adaptation to the phenological environment as rare advantageous phenotypes are driven to extinction when introduced in phases of the cycle where host populations are small and parasite populations are large. The results demonstrate that seasonal environments can drive population cycling in a restricted set of phenological patterns and provides further evidence that the rate of adaptive evolution depends on underlying ecological dynamics.

ecology↗

bioRxiv2021

Host phenology drives the evolution of intermediate parasite virulence

AO_SCPLOWBSTRACTC_SCPLOWThe traditional mechanistic trade-offs resulting in a negative correlation between transmission and virulence are the foundation of nearly all current theory on the evolution of parasite virulence. Several ecological factors have been shown to modulate the optimal virulence strategies predicted from mechanistic trade-off models, but these ecological factors have not yet been shown to be sufficient to explain the intermediate virulence strategies observed in any natural system. The timing of seasonal activity, or phenology, is a common factor that influences the types and impact of many ecological interactions but is difficult to incorporate into virulence evolution studies. We develop a mathematical model of a disease system with seasonal host activity to study the evolutionary consequences of host phenology on the virulence of obligate-killer parasite. Results from this model demonstrated that seasonal host activity is sufficient to drive the evolution of intermediate parasite virulence in some types of natural disease systems, even when a traditional mechanistic trade-off between transmission and virulence is not assumed in the modeling framework. The optimal virulence strategy in these systems can be determined by both the duration of the host activity period as well as the variation in the host emergence timing. Parasites with low virulence strategies are favored in environments with long host activity periods and in environments in which hosts emerge synchronously. The results demonstrate that host phenology can be sufficient to select for intermediate optimal virulence strategies, providing an alternative mechanism to account for virulence evolution in some natural systems.

evolutionary biology↗

bioRxiv2019

The role of host phenology for parasite transmission

Phenology is a fundamental determinant of species distributions, abundances, and interactions. In host-parasite interactions, host phenology can affect parasite fitness due to the temporal constraints it imposes on host contact rates. However, it remains unclear how parasite transmission is shaped by the wide range of phenological patterns observed in nature. We develop a mathematical model of the Lyme disease system to study the consequences of differential tick developmental-stage phenology for the transmission of B. burgdorferi. Incorporating seasonal tick activity can increase B. burgdorferi fitness compared to continuous tick activity but can also prevent transmission completely. B. burgdorferi fitness is greatest when the activity period of the infectious nymphal stage slightly precedes the larval activity period. Surprisingly, B. burgdorferi is eradicated if the larval activity period begins long after the end of nymphal activity due to a feedback with mouse population dynamics. These results highlight the importance of phenology, a common driver of species interactions, for the fitness of a parasite.

ecology↗

bioRxiv2019

Impaired Desynchronization of Beta Activity Underlies Memory Deficits in People with Parkinson’s Disease

There is a pressing need to better understand the mechanisms underpinning the increasingly recognised non-motor deficits in Parkinsons disease. Brain activity during Parkinsons disease is excessively synchronized within the beta range (12-30Hz). However, relatively little is known about how the abnormal beta rhythms impact on non-motor symptoms. In healthy adults, beta desynchronization is necessary for successful episodic memory formation. We investigated whether there was a direct relationship between decreased beta modulation and memory formation in Parkinsons disease. Electroencephalography recordings were made during an established memory-encoding paradigm. Parkinsons participants showed impaired memory strength (P = 0.023) and reduced beta desynchronization (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta desynchronization, and a concomitant reduction in memory performance. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinsons disease.

neuroscience↗

bioRxiv2019

Socio-spatial heterogeneity in participation in mass dog vaccination campaigns, Arequipa, Peru

To control and prevent rabies in Latin America, mass dog vaccination campaigns (MDVC) are implemented mainly through fixed-location vaccination points: owners have to bring their dogs to the vaccination points where they receive the vaccination free of charge. Dog rabies is still endemic in some Latin-American countries and high overall dog vaccination coverage and coverage evenness are desired attributes of MDVC to halt rabies virus transmission. In Arequipa, Peru, we conducted a door-to-door post-campaign survey on >6,000 houses to assess the placement of vaccination points on these two attributes. We found that the odds of participating in the campaign decreased by 16% for every 100 m from the owners house to the nearest vaccination point (p=0.041) after controlling for potential covariates. We found social determinants associated with participating in the MDVC: for each child under 5 in the household the odds of participating in the MDVC decreased by 13% (p=0.032), and for every ten more years living in the area, the odds of participating in the MDVC increased by 9% (p<0.001), after controlling for distance and other covariates. We also found significant spatial clustering of unvaccinated dogs over 500m from the vaccination points, which created pockets of unvaccinated dogs that may sustain rabies virus transmission. Understanding the barriers to dog owners participation in community-based dog-vaccination programs will be crucial to implement effective zoonotic disease preventive activities. Spatial and social elements of urbanization play an important role in coverage of MDVCs and should be considered during their planning and evaluation.

epidemiology↗