Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men.

Objective: To investigate the susceptibilities to and consequences of HIV-1 dual infection.

Design: We compared clinical, virologic, and immunologic factors between participants who were dually infected with HIV-1 subtype B and monoinfected controls who were matched by ongoing HIV risk factor.

Methods: The viral load and CD4 progressions of dually and singly infected participant groups were compared with linear mixed-effects models, and individual dynamics before and after superinfection were assessed with a structural change test (Chow test).

A random effects branch-site model for detecting episodic diversifying selection.

Adaptive evolution frequently occurs in episodic bursts, localized to a few sites in a gene, and to a small number of lineages in a phylogenetic tree. A popular class of "branch-site" evolutionary models provides a statistical framework to search for evidence of such episodic selection. For computational tractability, current branch-site models unrealistically assume that all branches in the tree can be partitioned a priori into two rigid classes--"foreground" branches that are allowed to undergo diversifying selective bursts and "background" branches that are negatively selected or neutral.

Detection of minority resistance during early HIV-1 infection: natural variation and spurious detection rather than transmission and evolution of multiple viral variants.

Reports of a high frequency of the transmission of minority viral populations with drug-resistant mutations (DRM) are inconsistent with evidence that HIV-1 infections usually arise from mono- or oligoclonal transmission. We performed ultradeep sequencing (UDS) of partial HIV-1 gag, pol, and env genes from 32 recently infected individuals. We then evaluated overall and per-site diversity levels, selective pressure, sequence reproducibility, and presence of DRM and accessory mutations (AM).

Response to Comment on "The Origins of Sexually Transmitted HIV Among Men Who Have Sex with Men".

In this investigation, we evaluated explanations for the unusual degree of genetic diversity in HIV populations within the sampled seminal cell and plasma compartments observed in our previous study. These analyses included clonal sequencing of HIV DNA in peripheral blood mononuclear cells, ultradeep sequencing of HIV RNA in blood plasma, human leukocyte antigen (HLA) haplotyping of previously used samples, and a BLAST screen against both a local and public repository of HIV-1 sequences, and the investigations to determine whether these observations were secondary to contamination or artifact were unsuccessful. As there are very few HIV sequences from seminal cell tissues and transmission pairs described in the literature, future studies that evaluate more transmission pairs with sampling from multiple anatomic compartments and at multiple time points will most likely be required to resolve this controversy.

The relatedness of HIV epidemics in the United States-Mexico border region.

Phylogeography can improve the understanding of local and worldwide HIV epidemics, including the migration of subepidemics across national borders. We analyzed HIV-1 sequences sampled from Mexico and San Diego, California to determine the relatedness of these epidemics. We sampled the HIV epidemics in (1) Mexico by downloading all publicly available HIV-1 pol sequences from antiretroviral-naive individuals in GenBank (n = 100) and generating similar sequences from cohorts of injection drug users and female sex workers in Tijuana, Mexico (n = 27) and (2) in San Diego, California by pol sequencing well-characterized primary (n = 395) and chronic (n = 267) HIV infection cohorts.

CodonTest: modeling amino acid substitution preferences in coding sequences.

Codon models of evolution have facilitated the interpretation of selective forces operating on genomes. These models, however, assume a single rate of non-synonymous substitution irrespective of the nature of amino acids being exchanged. Recent developments have shown that models which allow for amino acid pairs to have independent rates of substitution offer improved fit over single rate models.

Correcting the bias of empirical frequency parameter estimators in codon models.

Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions of these models are almost always estimated using nucleotide frequencies observed in a sequence alignment, primarily as a matter of historical convention. In this note, we demonstrate that a popular class of such estimators are biased, and that this bias has an adverse effect on goodness of fit and estimates of substitution rates.

Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology.

Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in evolutionary biology. Since the original release in 2005, we have expanded the analysis options to include recently developed algorithmic methods for recombination detection, evolutionary fingerprinting of genes, codon model selection, co-evolution between sites, identification of sites, which rapidly escape host-immune pressure and HIV-1 subtype assignment. The traditional selection tools have also been augmented to include recent developments in the field.

Benchmarking multi-rate codon models.

The single rate codon model of non-synonymous substitution is ubiquitous in phylogenetic modeling. Indeed, the use of a non-synonymous to synonymous substitution rate ratio parameter has facilitated the interpretation of selection pressure on genomes. Although the single rate model has achieved wide acceptance, we argue that the assumption of a single rate of non-synonymous substitution is biologically unreasonable, given observed differences in substitution rates evident from empirical amino acid models.

Genome-wide analysis of the structure of the South African Coloured Population in the Western Cape.

Admixed populations present unique opportunities to discover the genetic factors underlying many multifactorial diseases. The geographical position and complex history of South Africa has led to the establishment of the unique admixed population known as the South African Coloured. Not much is known about the genetic make-up of this population, and the historical record is patchy.

Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutations.

In cardiac muscle, the troponin (cTn) complex is a key regulator of myofilament calcium sensitivity because it serves as a molecular switch required for translating myocyte calcium fluxes into sarcomeric contraction and relaxation. Studies of several species suggest that ectotherm chordates have myofilaments with heightened calcium responsiveness. However, genetic polymorphisms in cTn that cause increased myofilament sensitivity to activating calcium in mammals result in cardiac disease including arrhythmias, diastolic dysfunction, and increased susceptibility to sudden cardiac death.

The origins of sexually transmitted HIV among men who have sex with men.

Although it is known that most HIV-1 infections worldwide result from exposure to virus in semen, it has not yet been established whether transmitted strains originate as RNA virions in seminal plasma or as integrated proviral DNA in infected seminal leukocytes. We present phylogenetic evidence that among six transmitting pairs of men who have sex with men, blood plasma virus in the recipient is consistently more closely related to the seminal plasma virus in the source. All sequences were subtype B, and the env C2V3 of transmitted variants tended to have higher mean isoelectric points, contain potential N-linked glycosylation sites, and favor CCR5 co-receptor usage.

Experimental evidence indicating that mastreviruses probably did not co-diverge with their hosts.

Background: Despite the demonstration that geminiviruses, like many other single stranded DNA viruses, are evolving at rates similar to those of RNA viruses, a recent study has suggested that grass-infecting species in the genus Mastrevirus may have co-diverged with their hosts over millions of years. This "co-divergence hypothesis" requires that long-term mastrevirus substitution rates be at least 100,000-fold lower than their basal mutation rates and 10,000-fold lower than their observable short-term substitution rates. The credibility of this hypothesis, therefore, hinges on the testable claim that negative selection during mastrevirus evolution is so potent that it effectively purges 99.

Frequent toggling between alternative amino acids is driven by selection in HIV-1.

Host immune responses against infectious pathogens exert strong selective pressures favouring the emergence of escape mutations that prevent immune recognition. Escape mutations within or flanking functionally conserved epitopes can occur at a significant cost to the pathogen in terms of its ability to replicate effectively. Such mutations come under selective pressure to revert to the wild type in hosts that do not mount an immune response against the epitope.

Models of coding sequence evolution.

Probabilistic models of sequence evolution are in widespread use in phylogenetics and molecular sequence evolution. These models have become increasingly sophisticated and combined with statistical model comparison techniques have helped to shed light on how genes and proteins evolve. Models of codon evolution have been particularly useful, because, in addition to providing a significant improvement in model realism for protein-coding sequences, codon models can also be designed to test hypotheses about the selective pressures that shape the evolution of the sequences.

The transmission of Helicobacter pylori: the effects of analysis method and study population on inference.

Although much is known about the virulence of Helicobacter pylori, the transmission pathways for this bacterium are still unresolved. Transmission has been addressed through: (1) prevalence within families; (2) detection in fecal/oral environments; (3) detection in the abiotic/biotic environment; and (4) direct inference from strain similarity. Here, we review the molecular and biochemical methods used and discuss the relative merits of each.

Ecological speciation in South Atlantic island finches.

Examples of sympatric speciation in nature are rare and hotly debated. We describe the parallel speciation of finches on two small islands in the Tristan da Cunha archipelago in the South Atlantic Ocean. Nesospiza buntings are a classic example of a simple adaptive radiation, with two species on each island: an abundant small-billed dietary generalist and a scarce large-billed specialist.

Population growth confounds phylogeographic inference in Namaqua sandgrouse.

The Namaqua sandgrouse, Pterocles namaqua, is a highly nomadic granivore of semiarid to arid habitats. As a result of nomadic movements in response to rainfall, the size of the breeding population in any one area fluctuates dramatically between breeding seasons. This high mobility in response to spatial and temporal abundance of food resources is expected to result in little population genetic structuring.

A population genetics pedigree perspective on the transmission of Helicobacter pylori.

The inference of transmission pathways for medicinally important bacteria is important to our understanding of pathogens. Here we report analyses of transmission in Helicobacter pylori, a major carcinogen. Our study is novel in that the focal community comprises detailed family pedigrees and has a high prevalence of H.

Incidence of Helicobacter felis and the effect of coinfection with Helicobacter pylori on the gastric mucosa in the African population.

Helicobacter pylori and Helicobacter felis are two of the Helicobacter spp. that infect humans. H.

Investigating the origin and spread of hepatitis C virus genotype 5a.

Epidemiological and phylogenetic studies of hepatitis C virus (HCV) have identified six major HCV genotypes and have attempted to characterize their origin and spread worldwide. Putative regions of endemic infection have been identified for all HCV genotypes except HCV genotype 5a. Although HCV genotype 5a was previously thought to be largely restricted to the northern part of South Africa, this study reports an unexpected cluster of the genotype in West Flanders Province in Belgium.

Characterization and evolution of the mitochondrial DNA control region in hornbills (Bucerotiformes).

We determined the mitochondrial DNA control region sequences of six Bucerotiformes. Hornbills have the typical avian gene order and their control region is similar to other avian control regions in that it is partitioned into three domains: two variable domains that flank a central conserved domain. Two characteristics of the hornbill control region sequence differ from that of other birds.