Publications by authors named "Paul M Sharp"

Genes encoded within organelle genomes often evolve at rates different from those in the nuclear genome. Here, we analyzed the relative rates of nucleotide substitution in the mitochondrial, apicoplast, and nuclear genomes in four different lineages of Plasmodium species (malaria parasites) infecting mammals. The rates of substitution in the three genomes exhibit substantial variation among lineages, with the relative rates of nuclear and mitochondrial DNA being particularly divergent between the Laverania (including Plasmodium falciparum) and Vivax lineages (including Plasmodium vivax).

View Article and Find Full Text PDF

The geographic origin of Plasmodium vivax, a leading cause of human malaria, has been the subject of much speculation. Here we review the evolutionary history of P. vivax and P.

View Article and Find Full Text PDF

Plasmodium ovale was the last of the exclusively human malaria parasites to be described, in 1922, and has remained the least well studied. Beginning in 1995, two divergent forms of the parasite, later termed 'classic' and 'variant', were described. By 2010, it was realised that these forms are two closely related, but genetically distinct and non-recombining species; they were given the names Plasmodium ovale curtisi and Plasmodium ovale wallikeri.

View Article and Find Full Text PDF

Ubiquitin is an extraordinarily highly conserved 76 amino acid protein encoded by three different types of gene, where the primary translation products are fusions either of ubiquitin with one of two ribosomal proteins (RPs) or of multiple ubiquitin monomers from head to tail. Here, we investigate the evolution of ubiquitin genes in mammalian malaria parasites (Plasmodium species). The ubiquitin encoded by the RPS27a fusion gene is highly divergent, as previously found in a variety of protists.

View Article and Find Full Text PDF

The malaria parasite Plasmodium falciparum causes substantial human mortality, primarily in equatorial Africa. Enriched in affected African populations, the B*53 variant of HLA-B, a cell surface protein that presents peptide antigens to cytotoxic lymphocytes, confers protection against severe malaria. Gorilla, chimpanzee, and bonobo are humans' closest living relatives.

View Article and Find Full Text PDF

The human parasite Plasmodium malariae has relatives infecting African apes (Plasmodium rodhaini) and New World monkeys (Plasmodium brasilianum), but its origins remain unknown. Using a novel approach to characterise P. malariae-related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa.

View Article and Find Full Text PDF

The selection of the elements to combine delimits the possible outcomes of synthetic chemistry because it determines the range of compositions and structures, and thus properties, that can arise. For example, in the solid state, the elemental components of a phase field will determine the likelihood of finding a new crystalline material. Researchers make these choices based on their understanding of chemical structure and bonding.

View Article and Find Full Text PDF

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species.

View Article and Find Full Text PDF

Type 1 interferons (IFN-I) are potent innate antiviral effectors that constrain HIV-1 transmission. However, harnessing these cytokines for HIV-1 cure strategies has been hampered by an incomplete understanding of their antiviral activities at later stages of infection. Here, we characterized the IFN-I sensitivity of 500 clonally derived HIV-1 isolates from the plasma and CD4 T cells of 26 individuals sampled longitudinally after transmission or after antiretroviral therapy (ART) and analytical treatment interruption.

View Article and Find Full Text PDF

African apes harbor at least twelve species, some of which have been a source of human infection. It is now well established that emerged following the transmission of a gorilla parasite, perhaps within the last 10,000 years, while emerged earlier from a parasite lineage that infected humans and apes in Africa before the Duffy-negative mutation eliminated the parasite from humans there. Compared to their ape relatives, both human parasites have greatly reduced genetic diversity and an excess of nonsynonymous mutations, consistent with severe genetic bottlenecks followed by rapid population expansion.

View Article and Find Full Text PDF

We present a new method of evolving crystal structures for crystal structure prediction. The method of chemically directed structure evolution uses chemical models to quantify the environment of atoms and vacancy sites in a crystal structure, with that information used to inform how to modify the structure to make a move on the potential energy surface. We have developed a method of chemically directed swapping, where we swap atoms in the least favourable chemical environments.

View Article and Find Full Text PDF

With the goal of finding new lithium solid electrolytes by a combined computational-experimental method, the exploration of the Li-Al-O-S phase field resulted in the discovery of a new sulfide LiAlS. The structure of the new phase was determined through an approach combining synchrotron X-ray and neutron diffraction with Li and Al magic-angle spinning nuclear magnetic resonance spectroscopy and revealed to be a highly ordered cationic polyhedral network within a sulfide anion -type sublattice. The originality of the structure relies on the presence of AlS repeating dimer units consisting of two edge-shared Al tetrahedra.

View Article and Find Full Text PDF

The Laverania clade comprises the human malaria parasite Plasmodium falciparum as well as at least seven additional parasite species that infect wild African apes. A recent analysis of Laverania genome sequences (Otto TD, et al. 2018.

View Article and Find Full Text PDF

Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes.

View Article and Find Full Text PDF

Forests and woodlands worldwide are being severely impacted by invasive species, with initial outbreaks in some cases occurring on host trees located in public parks and gardens. These highly disturbed sites with diverse planting practices may indeed act as harbours for invasive pathogens which are particularly well adapted to surviving in soil. High throughput Illumina sequencing was used to analyse species diversity in soil samples collected from 14 public garden/amenity woodland sites in northern Britain.

View Article and Find Full Text PDF

Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4 T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.

View Article and Find Full Text PDF

Short tandem repeats (STRs), also known as microsatellites, are commonly used to noninvasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise.

View Article and Find Full Text PDF
Article Synopsis
  • Wild-living African apes carry parasites closely related to those that cause malaria in humans, indicating that the origin of human malaria is linked to Africa.
  • Genome analysis of ape strains reveals a close genetic similarity to human strains, with only a small percentage of differences, but human strains show significantly less diversity.
  • Research suggests that human malaria parasites have a history of population bottlenecks and rapid expansion after leaving Africa, along with no significant barriers preventing infection across species.
View Article and Find Full Text PDF

African apes are endemically infected with numerous Plasmodium spp. including close relatives of human Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. Although these ape parasites are not believed to pose a zoonotic threat, their ability to colonise humans has not been fully explored.

View Article and Find Full Text PDF