Biology subjects

Haffener, P. E.

Publications and source records attributed to Haffener, P. E..

3 recordsLinked to original sources

bioRxiv2024

Phylogenetics and genomic variation of two genetically distinct Hepatocystis clades isolated from shotgun sequencing of wild primate hosts

Hepatocystis are apicomplexan parasites nested within the Plasmodium genus that infect primates and other vertebrates, yet few isolates have been genetically characterized. Using taxonomic classification and mapping characteristics, we searched for Hepatocystis infections within publicly available, blood-derived low coverage whole genome sequence (lcWGS) data from 326 wild non-human primates (NHPs) in 17 genera. We identified 30 Hepatocystis infections in Chlorocebus and Papio samples collected from locations in west, east, and south Africa. Hepatocystis cytb sequences from Papio hosts phylogenetically clustered with previously reported isolates from multiple NHP taxa whereas sequences from Chlorocebus hosts form a separate cluster, suggesting they represent a new host-specific clade of Hepatocystis. Additionally, there was no geographic clustering of Hepatocystis isolates suggesting both clades of Hepatocystis could be found in NHPs throughout sub-Saharan Africa. Across the genome, windows of high SNP density revealed candidate hypervariable loci including Hepatocystis-specific gene families possibly involved in immune evasion and genes that may be involved in adaptation to their insect vector and hepatocyte invasion. Overall, this work demonstrates how lcWGS data from wild NHPs can be leveraged to study the evolution of apicomplexan parasites and potentially test for association between host genetic variation and parasite infection. Author SummaryNon-human primates are hosts to many species of Plasmodium, the parasites that cause malaria, and a closely related group of parasites called Hepatocystis. However, due to restrictions and challenges of sampling from wild populations, we lack a complete understanding of the breadth of diversity and distribution of these parasites. Here, we provide a framework for testing already-sampled populations for parasite infections using whole genome sequences derived from whole blood samples from the host. Following taxonomic classification of these sequences using a database of reference genomes, we mapped reads to candidate parasite genomes and used an unsupervised clustering algorithm including coverage metrics to further validate infection inferences. Through this approach, we identified 30 Hepatocystis infections from two genetically distinct clades of Hepatocystis in African non-human primates and described genes that may be under immune selection in each. Most importantly, the framework here can be applied to additional sequencing datasets from non-human primates and other vertebrate hosts as well as datasets from invertebrate vectors. Therefore, this approach could greatly improve our understanding of where these parasites are found, their host-specificity, and their evolutionary history. This framework may also be adapted to study evolution in other host-pathogen groups.

evolutionary biology↗

bioRxiv2024

Characterization of Blood Group Variants in an Omani Population by Comparison of Whole Genome Sequencing and Serology

Although blood group variation was first described over a century ago, our understanding of the genetic variation affecting antigenic expression on the red blood cell surface in many populations is lacking. This deficit limits the ability to accurately type patients, especially as serological testing is not available for all described blood groups, and targeted genotyping panels may lack rare or population-specific variants. Here, we perform serological assays across 24 antigens and whole genome sequencing on 100 Omanis, a population underrepresented in genomic databases. We inferred blood group phenotypes using the most commonly typed genetic variants. The comparison of serological to inferred phenotypes resulted in an average concordance of 96.9%. Among the 22 discordances, we identify seven known variants in four blood groups that, to our knowledge, have not been previously reported in Omanis. Incorporating these variants for phenotype inference, concordance increases to 98.8%. Additionally, we describe five candidate variants in the Lewis, Lutheran, MNS, and P1 blood groups that may affect antigenic expression, although further functional confirmation is required. Notably, we identify several blood group alleles most common in African populations, likely introduced to Oman by gene flow over the last thousand years. These findings highlight the need to evaluate individual populations and their population history when considering variants to include in genotype panels for blood group typing. This research will inform future work in blood banks and transfusion services. Key PointsO_LIUtilizing whole genome sequencing to infer blood types in Omanis demonstrates high sensitivity for most blood groups C_LIO_LIPopulation history influences blood group variation, necessitating population-specific genotype panels C_LI

genomics↗

bioRxiv2024

Adaptive admixture at ACKR1 (the Duffy locus) may have shaped Plasmodium vivax prevalence in Oman

Malaria in humans is largely caused by two divergent species of Plasmodium parasites, P. vivax and P. falciparum, both of which have driven the spread of protective alleles in human populations. Notably, an erythrocyte-specific Duffy null allele (FyES) confers resistance to P. vivax malaria and has been identified as a target of strong, recent positive selection in multiple African admixed populations. Here, we evaluate evidence for selection via adaptive admixture in Oman, where compared to neighboring countries, P. vivax has recently been less common. Genetic ancestry inference using whole genome sequence data from 100 Omanis suggests 9.8% (95% CI: 7.3-12.2%) of their genetic ancestry is shared with east Africa. At the Duffy locus, we find a high frequency of FyES and an increase to 76% African ancestry. Comparing with blood group serology for the same individuals, we identify an additional Duffy-null allele that is rare but present across multiple Arabian Peninsula (AP) populations. Finally, we estimate the selection coefficient at FyES as 0.031 (95% CI: 0.029-0.034) with likely introduction at least 59 generations ago, older than estimates in other African admixed populations. Although we also observe higher frequency of some P. falciparum-protective alleles in Oman than in other AP populations, African ancestry is not enriched indicating a lack of evidence for adaptive admixture driven by P. falciparum selective pressure. Together, our analyses suggest that Omans long history with east African populations resulted in early introduction and selection for Duffy null alleles and may have influenced the prevalence of P. vivax in the region.

genetics↗