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
- Cornejo OE, Fisher D, Escalante AA. (2015) Genome-wide patterns of genetic polymorphism and signatures of selection in Plasmodium vivax. Genome Biology and Evolution 7(1): 106-119. (Highlighted in Nature Reviews Microbiology in the News and Analysis – Genome Watchsection, March 2015)
- Pacheco MA, Battistuzzi FU, Junge RE, Cornejo OE, Williams CV, Landau I, Rabetafika L, Snounou G, Jones-Engel L, Escalante AA. (2011) Timing the origin of human malarial: the lemur puzzle. BMC Evolutionary Biology. doi: 10.1186/1471-2148-11-299.
- Krief S, Escalante AA, Pacheco MA, Mugisha L, André C, Halbwax M, Fischer A, Krief JM, Kasenene JM, Crandfield M, Cornejo OE, Chavatte JM, Lin C, Letourneur F, Grüner AC, McCutchan TF, Rénia L, Snounou G. On the diversity of malaria parasites in African Apes and the origin of Plasmodium falciparum from Bonobos. PLoS Pathogens 6(2): e1000765. doi:10.1371/journal.ppat.1000765.
- Cornejo OE, Escalante AA. (2006) The origin and age of Plasmodium vivax. Trends in Parasitology, 22(12): 558-563.
- Escalante AA, Cornejo OE, Freeland DE, Poe AC, Durrego E, Collins WE, Lal AA. (2005) A monkey’s tale: The origin of Plasmodium vivax as a human malaria parasite. Proceedings of the National Academy of Sciences (USA) 102(6).
- Escalante AA, Cornejo OE, Rojas A, Udhayakumar V, Lal AA. (2004) Assessing the effect of natural selection in malaria parasites. Trends in Parasitology, 20(8): 388-395.
- Xia, C., Wang, M., Yin , C., Cornejo, O.E., Hulbert, S.H., Chen. X. (2018) Genomic insights into host adaptationbetween the wheat stripe rust pathogen(Puccinia striiformisf. sp.tritici) andthe barley stripe rust pathogen(Puccinia striiformisf. sp.hordei) BMC Genomics 19(1):664.
- Xia C, Wang M, Yin C, Cornejo O.E., Hulbert S, Chen X. (2018) Genome sequence resources for the wheat stripe rust pathogen (Puccinia striiformis f. sp. tritici) and the barley stripe rust pathogen (Puccinia striiformis f. sp. hordei). Mol Plant Microbe Interact. doi: 10.1094/MPMI-04-18-0107-A.
- Xia, C., Wang, M., Cornejo, O.E., Jiwan, D.A., See, D.R., Chen, X. (2017). Secretome characterization and correlation analysis reveal putative pathogenicity mechanisms in the wheat stripe rust fungus Puccinia striiformis f. sp. tritici. Frontiers in Microbiology 2017;00-12. doi: 10.3389/fmicb.2017.02394.
- Miller EL, Evans BA, Cornejo OE, Roberts IS, Rozen DE. (2017). Pherotype polymorphism in Streptococcus pneumoniae has no obvious effects on population structure and recombination. Genome Biology and Evolution 9(10): 2546–2559. doi.org/10.1093/gbe/evx188
- Cornejo OE*, Hickey RJ, Suzuki H, Forney LJ*. (2017). Focusing the diversity of Gardnerella vaginalis through the lens of ecotypes. Evolutionary Applications 2017;00:1–13. https://doi.org/10.1111/eva.12555 (*co-corresponding authors)
- Pepperell CS, Casto AM, Kitchen A, Granka JM, Cornejo OE, Holmes EC, Birren B, Galagan J, Feldman MW (2013) The role of selection in shaping diversity of natural M. tuberculosis populations. PLoS Pathogens. 9(8): e1003543. doi: 10.1371/journal.ppat.1003543
- Cornejo OE, Lefébure T, Bitar PD, Lang P, Richards VP, Eilertson K, Do T, Beighton D, Zeng L, Ahn SJ, Burne RA, Siepel A, Bustamante CD, Stanhope MJ. (2013) Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans. Molecular Biology and Evolution. 30(4): 881-893. [Highlighted in Science: “How Sweet it is: genes show how bacteria colonized human teeth” by Ann Gibbons]
- Cornejo OE, McGee L, Rozen DE. (2010) Polymorphism in the competence peptide does not limit recombination in Streptococcus pneumoniae. Molecular Biology and Evolution. 27: 694-702.
- Levin BR, Cornejo OE. (2009) The Population and Evolutionary Dynamics of Homologous Gene Recombination in Bacteria. PLoS Genetics 5(8): e1000601. doi:10.1371/journal.pgen.1000601.
- Cornejo OE, Rozen DE, May RM, Levin BR. (2009) Oscillations in Continuous Culture Populations of Streptococcus pneumoniae: Population Dynamics and the Evolution of Clonal Suicide. Proceedings of the Royal Society B. 276(1659):999-1008.
- Cornejo OE, Lefébure T, Bitar PD, Lang P, Richards VP, Eilertson K, Do T, Beighton D, Zeng L, Ahn SJ, Burne RA, Siepel A, Bustamante CD, Stanhope MJ. (2013) Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans. Molecular Biology and Evolution. 30(4): 881-893. [Highlighted in Science: “How Sweet it is: genes show how bacteria colonized human teeth” by Ann Gibbons]
- Huynh, Ashley, Quackenbush, Corey and Cornejo, Omar E. (in preparation). Oral metagenomic data reveals a highly diverse and divergent oral microbiome in understudied Congolese populations.
- Dolan, Megan and Cornejo, Omar E. (in preparation). Diverse endophyte composition across highly divergent populations of the chocolate tree, Theobroma cacao L.