Microbial Genomics

We are interested in understanding the evolutionary history of microbes to provide a framework to identify and contextualize their adaptations to hosts.

Population Genomics of Malarial Parasites

Plasmodium, the causative agent of malaria, is one of the most interesting parasites that impacts human health worldwide. It is a parasite with a complex life cycle, that involves sexual reproduction in the mosquito (vector), and asexual stages in different tissues of its vertebrate host. We are interested in determining the evolutionary history of Plasmodium vivax. We develop new approaches for understanding the evolution of its genomic architecture and the generation of antigenic variation.

Asian Origin of Plasmodium vivax

Our work on Plasmodium phylogenetics and population genetics supports an Asian origin for one of the five human malaria parasites, Plasmodium vivax. This is relevant because the demographic history of the parasite is not consistent with the evolution of a mutation that confers resistance to infections by P. vivax in Africa. This is one of the many examples for why it is important to infer the evolutionary history of microbes and hosts to understand current distributions of mutations associated with virulence (pathogens) or resistance (hosts).

 

 

Distribution of signatures of selection along the genome of parasites

Our work demonstrated that the effective population size (Ne) of Plasmodium vivax changes along the chromosomes with a clear increase towards sub-telomeric regions. These results, together with the preferential localization of genes involved in host-pathogen interaction towards subtelomeric regions, were interpreted as selection acting on gene localization and not just accumulation of variation at the gene level. It is clear that selection also acts on specific genes, but our analyses suggested that most genes in P. vivax are constrained and under strong purifying selection.

 

Evolutionary Biology of Microbes

Ecology and evolution of bacteriocins

Agents that kill the organisms that produce them are intriguing puzzles for ecologists and evolutionary biologists. How can such “self-killing” agents, which on a first consideration appear to be a considerable disadvantage to the organisms that produce them, evolve and be maintained by natural selection?

Our work, at the intersection of experiments and mathematical modeling opened the door for an interesting hypothesis about the maintenance of self-killing agents with a set of testable hypotheses: if the toxin producing bacterium kills others more than it kills itself, then a highly deleterious trait like this can be maintained.

 

Evolutionary impact of recombination in bacteria

In bacteria, recombination is considered a rare event and not part of its reproductive process. Nevertheless, the importance that Horizontal Gene Transfer (HGT in a broad sense) plays in the adaptive evolution of bacteria species is increasingly recognized.  We often ask ourselves: why do bacteria maintain an intricate machinery for homologous gene recombination? What is the impact of homologous gene recombination on the maintenance and accessibility of standing genetic variation in populations where sex is not frequent and not linked to reproduction? These are questions that are not well understood.

With regards to the question about maintenance of recombination in bacteria: our theoretical work suggests that, once established in the population, the ability to recombine can be maintained in the population at the expense of its costs.

With regards to the evolutionary consequences of recombination: we have shown that G. vaginalis, a bacteria commonly associated with the development of bacterial vaginosis in women, has a large accessory genome, enriched with unique genes involved in metabolism of different carbohydrates sources, drug resistance, and virulence. We analyze the pangenome of the species borrowing the concept of ecotype to explain how these differences in gene content really reflect the differential ability of strains in different clades to thrive in different environments. Horizontal gene transfer is then a force that can facilitate the creation of ecotypes and contribute to functional diversification in bacteria.

 

Evolutionary history of microbes

The evolution of pathogens and commensals can be better understood in the context of important events in the evolution of the hosts. These events provide the necessary framework to identify adaptations in the microbes relevant to understand the outcome of the interaction between hosts and microbes.  For instance, our analysis of current Streptococcus mutans genomes allowed us to estimate the historical demographics of the species to show that: i) it has been growing exponentially since the origin of agriculture and ii) it acquired numerous genes, via HGT, that contributed to its adaptation to the new environment that resulted from the shift in diet in humans.

Host Microbiome Interactions

The microbial networks that live in and on the human body contain a huge number of of species that greatly vary across different tissues. Trying to understand relevant changes in the human microbiome requires a more through understanding of the pangenome composition of the species in the community.  We anticipate that in order to understand the interaction between host and microbiome will require the integration of host genetics, microbiome species and pangenome composition. We are studying the oral and vaginal microbiome of humans and primates, as well as the endophytes microbes in the Chocolate to understand how microbiome and host interact to generate emergent phenotypes like disease resistance.

 

Relevant publications