Biology subjects

Serre, D.

Publications and source records attributed to Serre, D..

3 recordsLinked to original sources

bioRxiv2018

Human Migration and the Spread of the Nematode Parasite Wuchereria bancrofti

The human disease lymphatic filariasis causes the debilitating effects of elephantiasis and hydrocele. Lymphatic filariasis currently affects the lives of 90 million people in 52 countries. There are three nematodes that cause lymphatic filariasis, Brugia malayi, B. timori, and Wuchereria bancrofti, but 90% of all cases of lymphatic filariasis are caused solely by W. bancrofti. Here we use population genomics to identify the geographic origin of W. bancrofti and reconstruct its spread. Previous genomic sequencing efforts have suffered from difficulties in obtaining Wb DNA. We used selective whole genome amplification to enrich W. bancrofti DNA from infected blood samples and were able to analyze 47 whole genomes of W. bancrofti from endemic locations in Haiti, Mali, Kenya, and Papua New Guinea. Our results are consistent with a Southeast Asia or East Asia origin for W. bancrofti spread around the globe by infecting migrating populations of humans. Austronesians probably introduced W. ban-crofti to Madagascar where later migrations moved it to continental Africa. From Africa, W. bancrofti spread to the New World during the transatlantic slave trade. The greater genetic diversity of W. bancrofti populations from Haiti are also consistent with genetic admixture from multiple source populations. Genome scans for locally adapted haplotypes identified genes associated with human immune suppression and insecticide sensitivity. Locally adapted haplotypes may provide a foundation to understand the distribution of W. bancrofti compared to that of other filarial nematodes and how populations may differ in response to eradication efforts.

evolutionary biology↗

bioRxiv2018

In vivo gene expression analyses provide unique insights on P. vivax gametocytogenesis and chloroquine response

Studies of gene expression have provided insights on the regulation of Plasmodium parasites. However, few studies have targeted P. vivax, the cause of one third of all human malaria cases outside Africa, due to the lack of in vitro culture system and the difficulties associated with studying clinical samples. Here, we describe robust RNA-seq profiles of P. vivax parasites generated directly from infected patient blood. Gene expression deconvolution analysis reveals that most parasite mRNAs derive from trophozoites and that the asynchronicity of P. vivax infections is unlikely to confound gene expression studies. We also show that gametocyte genes form two clusters of co-regulated genes, possibly indicating the independent regulation of male and female gametocytogeneses. Finally, despite a large effect on parasitemia, we find that chloroquine does not alter trophozoite gene expression. Overall, our study highlights the biological knowledge that can be gathered by directly studying P. vivax patient infections.\n\nImportancePlasmodium vivax is the second most common cause of human malaria worldwide but, since it cannot be cultured in the laboratory, its biology remains poorly understood. In this study, we describe the analysis of the parasite gene expression profiles generated from 26 patient infections. We show that the proportion of male and female parasites varies greatly among infections, suggesting that they are independently regulated. We also compare the gene expression profiles of the same infections before and after treatment with chloroquine, a common antimalarial, and show that the drug efficiently kills most P. vivax parasites but appears to have little effect on one specific parasite stage, the trophozoites, in contrast with the effect of the drug on P. falciparum. Overall, our study exemplifies the biological insights that can be gained from applying modern genomic tools to study this difficult human pathogen.

microbiology↗

bioRxiv2018

Genetic diversity in two Plasmodium vivax protein ligands for reticulocyte invasion

The interaction between Plasmodium vivax Duffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports of P. vivax infections in Duffy-negative individuals questions its unique role. To investigate the genetic diversity of the two main protein ligands for reticulocyte invasion, PvDBP and P. vivax Erythrocyte Binding Protein (PvEBP), we analyzed 458 isolates collected in Cambodia and Madagascar. First, we observed a high proportion of isolates with multiple copies PvEBP from Madagascar (56%) where Duffy negative and positive individuals coexist compared to Cambodia (19%) where Duffy-negative population is virtually absent. Whether the gene amplification observed is responsible for alternate invasion pathways remains to be tested. Second, we found that the PvEBP gene was less diverse than PvDBP gene (12 vs. 33 alleles) but provided evidence for an excess of nonsynonymous mutations with the complete absence of synonymous mutations. This finding reveals that PvEBP is under strong diversifying selection, and confirms the importance of this protein ligand in the invasion process of the human reticulocytes and as a target of acquired immunity. These observations highlight how genomic changes in parasite ligands improve the fitness of P. vivax isolates in the face of immune pressure and receptor polymorphisms.

genetics↗