Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance.

Plasmodium vivax invasion of human erythrocytes depends on the Duffy Binding Protein (PvDBP) which interacts with the Duffy antigen. PvDBP copy number has been recently shown to vary between P. vivax isolates in Sub-Saharan Africa. However, the extent of PvDBP copy number variation, the type of PvDBP multiplications, as well as its significance across broad samples are still unclear. We determined the prevalence and type of PvDBP duplications, as well as PvDBP copy number variation among 178 Ethiopian P. vivax isolates using a PCR-based diagnostic method, a novel quantitative real-time PCR assay and whole genome sequencing. For the 145 symptomatic samples, PvDBP duplications were detected in 95 isolates, of which 81 had the Cambodian and 14 Malagasy-type PvDBP duplications. PvDBP varied from 1 to >4 copies. Isolates with multiple PvDBP copies were found to be higher in symptomatic than asymptomatic infections. For the 33 asymptomatic samples, PvDBP was detected with two copies in two of the isolates, and both were the Cambodian-type PvDBP duplication. PvDBP copy number in Duffy-negative heterozygotes was not significantly different from that in Duffy-positives, providing no support for the hypothesis that increased copy number is a specific association with Duffy-negativity, although the number of Duffy-negatives was small and further sampling is required to test this association thoroughly

Phylotranscriptomic analysis uncovers a wealth of tissue inhibitor of metalloproteinases variants in echinoderms

Tissue inhibitors of metalloproteinases (TIMPs) help regulate the extracellular matrix (ECM) in animals, mostly by inhibiting matrix metalloproteinases (MMPs). They are important activators of mutable collagenous tissue (MCT), which have been extensively studied in echinoderms, and the four TIMP copies in humans have been studied for their role in cancer. To understand the evolution of TIMPs, we combined 405 TIMPs from an echinoderm transcriptome dataset built from 41 specimens representing all five classes of echinoderms with variants from protostomes and chordates. We used multiple sequence alignment with various stringencies of alignment quality to cull highly divergent sequences and then conducted phylogenetic analyses using both nucleotide and amino acid sequences. Phylogenetic hypotheses consistently recovered TIMPs as diversifying in the ancestral deuterostome and these early lineages continuing to diversify in echinoderms. The four vertebrate TIMPs diversified from a single copy in the ancestral chordate, all other copies being lost. Consistent with greater MCT needs owing to body wall liquefaction, evisceration, autotomy and reproduction by fission, holothuroids had significantly more TIMPs and higher read depths per contig. Ten cysteine residues, an HPQ binding site and several other residues were conserved in at least 70% of all TIMPs. The conservation of binding sites and the placement of echinoderm TIMPs involved in MCT modification suggest that ECM regulation remains the primary function of TIMP genes, although within this role there are a large number of specialized copies

Selection for resistance to oseltamivir in seasonal and pandemic H1N1 influenza and widespread co-circulation of the lineages

Background: In Spring 2009, a novel reassortant strain of H1N1 influenza A emerged as a lineage distinct from seasonal H1N1. On June 11, the World Heath Organization declared a pandemic - the first since 1968. There are currently two main branches of H1N1 circulating in humans, a seasonal branch and a pandemic branch. The primary treatment method for pandemic and seasonal H1N1 is the antiviral drug Tamiflu® (oseltamivir). Although many seasonal H1N1 strains around the world are resistant to oseltamivir, initially, pandemic H1N1 strains have been susceptible to oseltamivir. As of February 3, 2010, there have been reports of resistance to oseltamivir in 225 cases of H1N1 pandemic influenza. The evolution of resistance to oseltamivir in pandemic H1N1 could be due to point mutations in the neuraminidase or a reassortment event between seasonal H1N1 and pandemic H1N1 viruses that provide a neuraminidase carrying an oseltamivir-resistant genotype to pandemic H1N1. Results: Using phylogenetic analysis of neuraminidase sequences, we show that both seasonal and pandemic lineages of H1N1 are evolving to direct selective pressure for resistance to oseltamivir. Moreover, seasonal lineages of H1N1 that are resistant to oseltamivir co-circulate with pandemic H1N1 throughout the globe. By combining phylogenetic and geographic data we have thus far identified 53 areas of co-circulation where reassortment can occur. At our website POINTMAP, http://pointmap.osu.edu webcite we make available a visualization and an application for updating these results as more data are released. Conclusions: As oseltamivir is a keystone of preparedness and treatment for pandemic H1N1, the potential for resistance to oseltamivir is an ongoing concern. Reassortment and, more likely, point mutation have the potential to create a strain of pandemic H1N1 against which we have a reduced number of treatment options

Fundamentos de la epidemiología genómica, lecciones aprendidas de la enfermedad por coronavirus (COVID-19) y nuevas direcciones

La pandemia de la enfermedad por coronavirus 2019 (COVID-19) fue una de las principales causas de muerte en todo el mundo en 2020. La enfermedad es causada por el coronavirus 2 (SARS-CoV-2), un virus de ARN de la subfamilia Orthocoronavirinae relacionado con otros 2 coronavirus clínicamente relevantes, SARS-CoV y MERS-CoV. Al igual que otros coronavirus y varios otros virus, el SARS-CoV-2 se originó en los murciélagos. Sin embargo, a diferencia de otros coronavirus, el SARS-CoV-2 resultó en una pandemia devastadora. La pandemia de SARS-CoV-2 continúa, debido a la evolución viral que conduce a variantes más transmisibles e inmunes evasivas. Tecnologías como la secuenciación genómica, ha impulsado el cambio de la epidemiología sindrómica a la molecular, y promete una mejor comprensión de las variantes. La pandemia de COVID-19 ha expuesto obstáculos críticos que deben abordarse para desarrollar la ciencia de las pandemias. Gran parte del progreso se está aplicando en el mundo desarrollado. Sin embargo, persisten las barreras para el uso de la epidemiología molecular en los países de ingresos bajos y medianos (LMIC), incluida la falta de logística para equipos y reactivos y la falta de capacitación en análisis. Revisamos la literatura de epidemiología molecular para comprender sus orígenes desde la epidemia de SARS (2002-2003) hasta los eventos de influenza y la pandemia actual de COVID-19. Abogamos por una mejor vigilancia genómica del SARS-CoV y por comprender la diversidad de patógenos en posibles huéspedes zoonóticos. Este trabajo requerirá capacitación en computación filogenética y de alto rendimiento para mejorar los análisis del origen y la propagación de patógenos. Los objetivos generales son comprender y reducir el riesgo de zoonosis a través de la colaboración interdisciplinaria y la reducción de las barreras logísticas

Polychrotid lizards

38 p. : ill. (1 col.) ; 26 cm.Includes bibliographical references (p. 15-18).Using the techniques of direct optimization and sensitivity analysis, the phylogenetics of polychrotid lizards were examined on the basis of both molecular and morphological data (ca. 1040 bp of 12S rDNA, valine tDNA, and 16S rDNA, and 82 characters of morphology). A sensitivity analysis of sequence alignment and morphological change cost functions demonstrated that equal weighting provided the most parsimonious solution for all data. The Polychrotidae is found not to be monophyletic, containing instead the Corytophanidae as the sister taxon of Anolis plus Polychrus. Based on these and other results over the last 12 years, the taxonomy of the Iguania is reformulated, with the Iguania composed of two subsidiary taxa, Acrodonta and Pleurodonta, the Acrodonta containing the likely paraphyletic and basally unresolved "Agamidae" as well as the Chamaeleonidae, and the Pleurodonta containing the Corytophanidae, Crotaphytidae, Hoplocercidae, Iguanidae, Leiocephalidae (newly elevated from its former status as a subfamily of the Tropiduridae), Leiosauridae (new taxon including Anisolepis, Aperopristis, Diplolaemus, Enyalius, Leiosaurus, Pristidactylus, and Urostrophus), Liolaemidae (newly elevated from its former status as a subfamily of the Tropiduridae), Opluridae, Phrynosomatidae, Polychrotidae (restricted to Anolis and Polychrus), and Tropiduridae (excluding the former subfamilies Leiocephalinae and Liolaeminae)

Discovery of adults linked to cloning oceanic starfish larvae (Oreaster, asteroidea: Echinodermata)

Two juvenile specimens of a new species of Oreaster were collected at Parque Nacional Arrecife Alacranes and Triángulos Oeste in the southern Gulf of Mexico. DNA of mitochondrial loci identifies them as members of the same clade as cloning larvae of Oreaster found abundantly in waters of the Florida Current-Gulf Stream system, and distinct from Oreaster clavatus and Oreaster reticulatus, the two known Oreasteridae species in the North Atlantic. Larvae from the new species of Oreaster persist as clones but also metamorphose and settle to the benthos with typical asteroid morphology. © 2019 The University of Chicago

Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale

Progress in Parasite Genomics and Its Application to Current Challenges in Malaria Control

A wide deployment of malaria control tools have significantly reduced malaria morbidity and mortality across Africa. However, in the last five to seven years, there has been a resurgence of malaria in several African countries, raising the questions of whether and why current control mechanisms are failing. Since the first Plasmodium falciparum reference genome was published in 2002, few thousands more representing a broad range of geographical isolates have been sequenced. These advances in parasite genomics have improved our understanding of mutational changes, molecular structure, and genetic mechanisms associated with diagnostic testing, antimalarial resistance, and preventive measures such as vaccine development. In this chapter, we summarize the current progress on: (1) genomic characteristics of P. falciparum; (2) novel biomarkers and revolutionary techniques for diagnosing malaria infections; and (3) current vaccine targets and challenges for developing efficacious and long-lasting malaria vaccines

Integration of phylogenomics and molecular modeling reveals lineage-specific diversification of toxins in scorpions

Scorpions have evolved a variety of toxins with a plethora of biological targets, but characterizing their evolution has been limited by the lack of a comprehensive phylogenetic hypothesis of scorpion relationships grounded in modern, genome-scale datasets. Disagreements over scorpion higher-level systematics have also incurred challenges to previous interpretations of venom families as ancestral or derived. To redress these gaps, we assessed the phylogenomic relationships of scorpions using the most comprehensive taxonomic sampling to date. We surveyed genomic resources for the incidence of calcins (a type of calcium channel toxin), which were previously known only from 16 scorpion species. Here, we show that calcins are diverse, but phylogenetically restricted only to parvorder Iurida, one of the two basal branches of scorpions. The other branch of scorpions, Buthida, bear the related LKTx toxins (absent in Iurida), but lack calcins entirely. Analysis of sequences and molecular models demonstrates remarkable phylogenetic inertia within both calcins and LKTx genes. These results provide the first synapomorphies (shared derived traits) for the recently redefined clades Buthida and Iurida, constituting the only known case of such traits defined from the morphology of molecules