Multiple Merger Genealogies in Outbreaks of Mycobacterium tuberculosis

The Kingman coalescent and its developments are often considered among the most important advances in population genetics of the last decades. Demographic inference based on coalescent theory has been used to reconstruct the population dynamics and evolutionary history of several species, including Mycobacterium tuberculosis (MTB), an important human pathogen causing tuberculosis. One key assumption of the Kingman coalescent is that the number of descendants of different individuals does not vary strongly, and violating this assumption could lead to severe biases caused by model misspecification. Individual lineages of MTB are expected to vary strongly in reproductive success because 1) MTB is potentially under constant selection due to the pressure of the host immune system and of antibiotic treatment, 2) MTB undergoes repeated population bottlenecks when it transmits from one host to the next, and 3) some hosts show much higher transmission rates compared with the average (superspreaders).Here, we used an approximate Bayesian computation approach to test whether multiple-merger coalescents (MMC), a class of models that allow for large variation in reproductive success among lineages, are more appropriate models to study MTB populations. We considered 11 publicly available whole-genome sequence data sets sampled from local MTB populations and outbreaks and found that MMC had a better fit compared with the Kingman coalescent for 10 of the 11 data sets. These results indicate that the null model for analyzing MTB outbreaks should be reassessed and that past findings based on the Kingman coalescent need to be revisited.     

Modeling the Potential Impact of Host Population Survival on the Evolution of M. tuberculosis Latency

Tuberculosis (TB) is an infectious disease with a peculiar feature: Upon infection with the causative agent, Mycobacterium Tuberculosis (MTB), most hosts enter a latent state during which no transmission of MTB to new hosts occurs. Only a fraction of latently infected hosts develop TB disease and can potentially infect new hosts. At first glance, this seems like a waste of transmission potential and therefore an evolutionary suboptimal strategy for MTB. It might be that the human immune response keeps MTB in check in most hosts, thereby preventing it from achieving its evolutionary optimum. Another possible explanation is that long latency and progression to disease in only a fraction of hosts are evolutionary beneficial to MTB by allowing it to persist better in small host populations. Given that MTB has co-evolved with human hosts for millenia or longer, it likely encountered small host populations for a large share of its evolutionary history and had to evolve strategies of persistence. Here, we use a mathematical model to show that indeed, MTB persistence is optimal for an intermediate duration of latency and level of activation. The predicted optimal level of activation is above the observed value, suggesting that human co-evolution has lead to host immunity, which keeps MTB below its evolutionary optimum.     

Temperature and pathogen exposure act independently to drive host phenotypic trajectories

Natural populations are experiencing an increase in the occurrence of both thermal stress and disease outbreaks. How these two common stressors interact to determine host phenotypic shifts will be important for population persistence, yet a myriad of different traits and pathways are a target of both stressors, making generalizable predictions difficult to obtain. Here, using the host Daphnia magna and its bacterial pathogen Pasteuria ramosa, we tested how temperature and pathogen exposure interact to drive shifts in multivariate host phenotypes. We found that these two stressors acted mostly independently to shape host phenotypic trajectories, with temperature driving a faster pace of life by favouring early development and increased intrinsic population growth rates, while pathogen exposure impacted reproductive potential through reductions in lifetime fecundity. Studies focussed on extreme thermal stress are increasingly showing how pathogen exposure can severely hamper the thermal tolerance of a host. However, our results suggest that under milder thermal stress, and in terms of life-history traits, increases in temperature might not exacerbate the impact of pathogen exposure on host performance, and vice versa.     

Molecular characterization of a glutathione peroxidase gene and its expression in the selected Vibrio-resistant population of the clam Meretrix meretrix

Glutathione peroxidase (GPx) is an important member of cellular enzymatic antioxidant system, which may be involved in pathogen defense of host. In the present study, a selenium-dependent glutathione peroxidase (MmeGPx) gene from clam Meretrix meretrix was cloned and analyzed. The MmeGPx gene was composed of two introns of 723 bp and 238 bp and an open reading frame (ORF) of 711 bp. The ORF encodes a protein of 237 amino acids with a putative selenocysteine residue encoded by an unusual stop codon. MmeGPx shares a higher level of similarity with human GPx 3 than with other human GPx isozymes. The level of MmeGPx mRNA roughly paralleled GPx enzyme activity in different tissues except in gills, with the highest mRNA expression and enzyme activity occurring in hepatopancreas. MmeGPx mRNA expressions were detected in different larval stages and the results showed that MmeGPx mRNA increased significantly in pediveliger stage, which may be a response to oxidative stress. After challenge of clam with a Vibrio parahaemolyticus-related bacterium (MM21), the expression of MmeGPx was significantly up-regulated at 6 h and 12 h in hepatopancreas, which suggested that MmeGPx may be involved in the immune response to MM21 infection. To better understand its role in the immunity of clam, the expression of MmeGPx in hepatopancreas was compared between a selected Vibrio-resistant population and a control population after immersion challenge with MM21. Early up-regulation of MmeGPx was observed in the resistant population. These results suggested that MmeGPx might be involved in maintaining the redox state of immune system, and the early immune response to pathogen infection may help the clam against pathogen infection.