bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.06.21.600103

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

Haffener, P. E.·Hopson, H. D.·Leffler, E. M.
View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Haffener, P. E., Hopson, H. D., Leffler, E. M.. 2024-06-27. Phylogenetics and genomic variation of two genetically distinct Hepatocystis clades isolated from shotgun sequencing of wild primate hosts. https://doi.org/10.1101/2024.06.21.600103

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Denisovan introgression left differential selection regimes in Humans and Neanderthals on the SLC30A9 gene

Signals of positive selection around the SLC30A9 gene have been reported in human populations outside Africa. Selection likely acted on a highly differentiated single-nucleotide polymorphism, rs1047626, leading to a non-synonymous substitution in the encoded zinc transporter. Because of the striking similarity between the putatively selected SLC30A9 haplotype observed in several current human populations and the Denisovan individual, previous work has proposed adaptive introgression. Yet alternative explanations, including ancient human variation, and the precise archaic source -Neanderthal or Denisovan- remained unresolved. Considering the potentially complex evolution of SLC30A9, we applied Approximate Bayesian Computation (ABC) algorithms coupled to machine learning to investigate the most plausible evolutionary origin of this substitution. After modelling different evolutionary scenarios with forward-in-time simulations, our results highlight that the most probable scenario is a Denisovan origin of the rs1047626 polymorphism. However, the allele likely introgressed into Neanderthals first and was then passed into non-African modern humans. Moreover, the derived allele frequency for rs1047626 across several African populations is consistent with back-to-Africa migrations. Finally, our ABC analyses indicate strong positive selection in East Asian populations and other out-of-Africa populations, whereas in Neanderthal populations, the selection coefficient was probably neutral or slightly deleterious.

evolutionary biology↗
bioRxiv2026

RELAX does not reproduce its own estimates at default settings, and its output does not show it

Selection-intensity estimates from RELAX are reported as a point value of K with a likelihood-ratio P. We report that, at default settings and on data of ordinary size, the program does not reproduce its own fits. Of 27 enzyme entries refitted under two optimiser configurations, none reproduced its log-likelihood to within 0.01 units; the median change was 103 units, the largest over 3,400, and four verdicts reversed. Eighty null orthologues reproduced none. A byte-identical command returned a distinct likelihood on every repetition, single-threaded, across three releases, and on alignments simulated under the fitted model, where 3.3 per cent of replicates reproduced. The documented random-number seed never reaches the generator when assigned on the command line, yet reads back as the value supplied. PAML localises the cause: its two-ratio model, without site classes, reproduced its log-likelihood for all 288 genes; its site-class models agreed for 27 to 67 per cent. The instability follows the mixture over sites, not the program. The output does not show it: 46 of 410 fits ended with a negative likelihood-ratio statistic, impossible under convergence, and 123 of 410 report a K re-estimated under a domain restriction rather than the unconstrained maximum. Of 234 published studies using RELAX, none reported a seed. Seeding while holding the thread count at one reproduced sixty of sixty runs on twenty genes under two releases; the seed alone reproduced none of five, and no documentation states the second condition. We recommend that fits be repeated and their dispersion published.

evolutionary biology↗
bioRxiv2026

Sequential accumulation of adaptive alleles forms an inversion supergene in deer mice

Supergenes are clusters of co-inherited loci that affect multiple or complex phenotypes. Despite the growing number of chromosomal inversions identified as supergenes in natural populations, their molecular basis and evolutionary history often remain obscure. Here, we identified two candidate genes, Slc45a2 and Npr3, within a 41-Mb inversion supergene in the deer mouse (Peromyscus maniculatus) that respectively drive darker coats and longer tails - two traits associated with forest adaptation. Mice homozygous for the inversion (inv/inv) exhibit elevated Slc45a2 expression in melanocytes relative to the congenic standard genotype (std/std), disrupting pheomelanin production. In parallel, downregulation of Npr3 in inv/inv mouse growth plates prolongs postnatal growth of caudal vertebrae, resulting in tail elongation. Population-level analyses further implicate that this supergene arose through the subsequent accumulation of the Npr3 allele within the inversion, rather than by capturing all beneficial mutations at its origin.

evolutionary biology↗