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Neurocognitive consequences of HIV in southern India: a preliminary study of clade C virus.

The neurocognitive impact of the clade C viral strain of human immunodeficiency virus (HIV) has not been determined. The purpose of this study was to examine neurocognitive function in southern India among individuals with the clade C virus with advanced HIV. A battery of cognitive tasks sensitive to the effects of HIV on brain function was translated and administered in Tamil and Telegu, two widely spoken languages in southern India. A sample of 30 treatment-naïve HIV-positive individuals with a median CD4 cell count of 97, and 30 age and education matched healthy controls obtained from the same region of India, were included in the study. Results revealed significant differences on most cognitive tests, with lower performances obtained by the HIV-positive individuals. These results suggest that cognitive difficulties are present among individuals with the clade C virus in India, with as many as 56% of the patients with advanced HIV meeting the criterion for impairment in two cognitive domains. Additional study is needed to determine if clade C HIV infection is more or less prone to cause neurocognitive deficit than the clade B virus. Furthermore, the impact of antiretroviral therapy on neurocognitive dysfunction in clade C virual infection needs to be determined.

Adult↗

Hepatitis C virus: clades and properties.

Hepatitis C virus (HCV) is a member of the virus family Flaviviridae. At present HCV is classified into a discrete hepacivirus genus and is represented by six clades according to genome sequencing. Each clade is further divisible into subtypes, which may prove important for the study of clinical differences and epidemiological studies. Limited homology also exists with hepatitis G/GB viruses, despite the fact that the hepatotropic nature of the latter agents remains contentious. The variability amongst the six HCV clades is less than that observed between the four serotypes of dengue, suggesting that each clade may represent a distinct virus were tests such as plaque neutralization to become available for delineating HCV isolates. The distribution worldwide varies, with Clades 1 and 2 predominating in most regions-an important consideration for the development of any vaccine. In addition, the clade distribution among cohorts may vary according to age. Point source outbreaks of HCV, for example in large numbers of women inadvertently infected with HCV-contaminated anti-D globulin, offers an opportunity to study the evolution of HCV genotypes over several decades. Parallel studies in chimpanzees have shown that the hypervariable region of E2 may play a role in HCV immunity, with quasispecies rapidly replacing the predominant subtype as immunity develops to the initiating virus strain. There is some evidence that an IFN-sensitive motif exists in the NS5 gene which may have some predictive value in determining the likely outcome of IFN treatment. A database is available for all HCV sequences, together with information about their properties and guidance for the evaluation of new isolates (http://s2as02.genes.nig.ac.jp).

Age Factors↗

Small clades at the periphery of passerine morphological space.

Among passerine birds (order Passeriformes), tribe- to family-level clades with five or fewer species are more frequent than one would expect from a homogeneous speciation and extinction process. Previous analyses also suggested that small clades tend to be marginal geographically and/or ecologically. In this study, I use principal component (PC) scores based on eight log-transformed measurements of the wing, tail, leg, and beak to test the hypothesis that small clades (<or=5 species) occupy peripheral positions in morphological space. Species in smaller clades exhibited higher absolute deviations and greater standard deviations on PC axes 4, 6, and 7, reflecting peripheral positions associated with relatively long toes, sometimes in contrast with short legs, and relatively small beaks compared with other birds. These extreme morphological characters are related to foraging on hard substrates, such as rock or bark, or feeding from perched positions or in dense vegetation. The implication that these small clades are protected from extinction at the periphery of morphological and, by inference, ecological space suggests that more detailed studies of the evolution and ecology of species in small clades should be a priority.

Adaptation, Physiological↗

Monophyletic clade of HIV-1 subtype B in Korea: evolutionary pressure or single introduction?

We have previously shown that many of the nef sequences from Korean HIV-1 subtype B carriers were grouped together in phylogenetic tree analyses. To determine whether this pattern was originated from either a single HIV-1-infected person or some biological pressure which directs the HIV-1 genomic mutation by the Korean specific immunological characters, we analyzed nef sequences from HIV-1-infected individuals with different time intervals. Thirty-two out of 46 analyzed patients formed a Korean monophyletic (KM) clade with 93% bootstrapping value. Eighteen patients' nef sequences were analyzed 1-9 years after first analysis. None of the patients shifted their clade from the first clustered clade (KM or non-KM), and all of the re-analyzed isolates were clustered close to the first analyzed clade. Isolates of the KM dade and non-KM clade in nef analysis showed the same pattern as in env analysis. Phylogenetic clustering evidences from both nef and C2/V3 trees strongly support the idea that introduction of the KM clade in subtype B strains originated from a common source. Thus, treatment and development of an AIDS vaccine may be somewhat easier than in other countries with multiple strains of HIV-1.

Biological Evolution↗

Comparative Phylogenetics Reveal Clade-specific Drivers of Recombination Rate Evolution Across Vertebrates.

Meiotic recombination is an integral cellular process, required for the production of viable gametes. Recombination rate is a fundamental genomic parameter, modulating genomic responses to selection. Our increasingly detailed understanding of its molecular underpinnings raises the prospect that we can gain insight into trait divergence by examining the molecular evolution of recombination genes from a pathway perspective, as in mammals, where protein-coding changes in later stages of the recombination pathway are connected to divergence in intra-clade recombination rate. Here, we leverage increased availability of avian and teleost genomes to reconstruct the evolution of the recombination pathway across two additional vertebrate clades: birds, which have higher and more variable rates of recombination and similar divergence times to mammals, and teleost fish, which have much deeper divergence times. Rates of molecular evolution of recombination genes are highly correlated between vertebrate clades and significantly elevated compared to control panels, suggesting that they experience similar selective pressures. Avian recombination genes are significantly more likely to exhibit signatures of positive selection than other clades, unrestricted to later stages of the pathway. Signatures of positive selection in genes linked to recombination rate variation in mammalian populations and those with signatures of positive selection across the avian phylogeny are highly correlated. In contrast, teleost fish recombination genes have significantly less evidence of positive selection despite high intra-clade recombination rate variability. Gaining clade-specific understanding of patterns of variation in recombination genes can elucidate drivers of recombination rate and thus, factors influencing genetic diversity, selection efficacy, and species divergence.

Animals↗

Evolution of target specificity in R1 clade non-LTR retrotransposons.

Although most non-long terminal repeat (non-LTR) retrotransposons are inserted throughout the host genome, many non-LTR elements in the R1 clade are inserted into specific sites within the target sequence. Four R1 clade families have distinct target specificity: R1 and RT insert into specific sites of 28S rDNA, and TRAS and SART insert into different sites within the (TTAGG)(n) telomeric repeats. To study the evolutionary history of target specificity of R1-clade retrotransposons, we have screened extensively novel representatives of the clade from various insects by in silico and degenerate polymerase chain reaction (PCR) cloning. We found four novel sequence-specific elements; Waldo (WaldoAg1, 2, and WaldoFs1) inserts into ACAY repeats, Mino (MinoAg1) into AC repeats, R6 into another specific site of the 28S rDNA, and R7 into a specific site of the 18S rDNA. In contrast, several elements (HOPE, WISHBm1, HidaAg1, NotoAg1, KagaAg1, Ha1Fs1) lost target sequence specificity, although some of them have preferred target sequences. Phylogenetic trees based on the RT and EN domains of each element showed that (1) three rDNA-specific elements, RT, R6, and R7, diverged from Waldo; (2) the elements having similar target sequences are phylogenetically related; and (3) the target specificity in the R1 clade was obtained once and thereafter altered and lost several times independently. These data indicate that the target specificity in R1 clade retroelements has changed during evolution and is more divergent than has been speculated so far.

Animals↗

The evolving story of Mycobacterium tuberculosis clade members detected in fish.

Advances in molecular analyses have permitted documentation of an increasing spectrum of mycobacteria infecting fish. Although some of these mycobacteria are not closely related, several species belong to the Mycobacterium tuberculosis clade. One member of the clade, M. marinum, is well known as an agent of piscine mycobacteriosis. Three other clade species, M. shottsii, M. pseudoshottsii and M. 'chesapeaki', have recently been identified as predominant disease agents in a widespread, continuing epizootic in wild striped bass of the Chesapeake Bay. A fifth clade member, M. ulcerans, has recently been indirectly detected in wild, African cichlid fish. As M. ulcerans is the third most common human mycobacterial infection worldwide, even such indirect evidence of M. ulcerans in fish must be more thoroughly investigated. Complicating the differentiation of these clade members is the growing recognition of intraspecies and interspecies variation in phenotypes, genes and virulence. Thus, researchers must be aware of the variety of piscine isolates within the M. tuberculosis clade. This review summarizes the methods of detection and differentiation for this important group of mycobacteria.

Animals↗

Aerobic anoxygenic photosynthesis in Roseobacter clade bacteria from diverse marine habitats.

The marine Roseobacter clade comprises several genera of marine bacteria related to the uncultured SAR83 cluster, the second most abundant marine picoplankton lineage. Cultivated representatives of this clade are physiologically heterogeneous, and only some have the capability for aerobic anoxygenic photosynthesis, a process of potentially great ecological importance in the world's oceans. In an attempt to correlate phylogeny with ecology, we investigated the diversity of Roseobacter clade strains from various marine habitats (water samples, biofilms, laminariae, diatoms, and dinoflagellate cultures) by using the 16S rRNA gene as a phylogenetic marker gene. The potential for aerobic anoxygenic photosynthesis was determined on the genetic level by PCR amplification and sequencing of the pufLM genes of the bacterial photosynthesis reaction center and on the physiological level by detection of bacteriochlorophyll (Bchl) a. A collection of ca. 1,000 marine isolates was screened for members of the marine Roseobacter clade by 16S rRNA gene-directed multiplex PCR and sequencing. The 42 Roseobacter clade isolates found tended to form habitat-specific subclusters. The pufLM genes were detected in two groups of strains from dinoflagellate cultures but in none of the other Roseobacter clade isolates. Strains within the first group (the DFL-12 cluster) also synthesized Bchl a. Strains within the second group (the DFL-35 cluster) formed a new species of Roseovarius and did not produce Bchl a under the conditions investigated here, thus demonstrating the importance of genetic methods for screening of cultivation-dependent metabolic traits. The pufL genes of the dinoflagellate isolates were phylogenetically closely related to pufL genes from Betaproteobacteria, confirming similar previous observations which have been interpreted as indications of gene transfer events.

Aerobiosis↗

A full-genome phylogenetic analysis of varicella-zoster virus reveals a novel origin of replication-based genotyping scheme and evidence of recombination between major circulating clades.

Varicella-zoster virus (VZV) is a remarkably stable virus that until recently was thought to exhibit near-universal genetic homogeneity among circulating wild-type strains. In recent years, the expanding knowledge of VZV genetics has led to a number of groups proposing sequence-based typing schemes, but no study has yet examined the relationships between VZV genotypes at a full-genome level. A central hypothesis of this study is that VZV has coevolved with humankind. In this study, 11 additional full VZV genomic sequences are presented, bringing the current number of complete genomic sequences publicly available to 18. The full-genome alignment contained strains representing four distinct clades, but the possibility exists that a fifth clade comprised of African and Asian-like isolates was not represented. A consolidated VZV genotyping scheme employing the origin-associated region between reiteration region R4 and open reading frames (ORFs) 63 and 70 is described, one which accurately categorizes strains into one of four clades related to the geographic origin of the isolates. The full-genome alignment also provided evidence for recombination having occurred between the major circulating VZV clades. One Canadian clinical isolate was primarily Asian-like in origin, with most of the genome showing strong sequence identity to the Japanese-like clade B, with the exceptions being two putative recombination regions, located in ORFs 14 to 17 and ORFs 22 to 26, which showed clear similarity to the European/North American clade A. The very low rate of single-nucleotide polymorphisms scattered across the genome made full-genome sequencing the only definitive method for identifying specific VZV recombination events.

Base Sequence↗

Infectious molecular clone of a recently transmitted pediatric human immunodeficiency virus clade C isolate from Africa: evidence of intraclade recombination.

Although human immunodeficiency virus type 1 (HIV-1) clade C continues to dominate the pandemic, only two infectious clade C proviral DNA clones have been described (N. Mochizuki, N. Otsuka, K. Matsuo, T. Shiino, A. Kojima, T. Kurata, K. Sakai, N. Yamamoto, S. Isomura, T. N. Dhole, Y. Takebe, M. Matsuda, and M. Tatsumi, AIDS Res. Hum. Retrovir. 15:1321-1324, 1999; T. Ndung'u, B. Renjifo, and M. Essex, J. Virol. 75:4964-4972, 2001). We have generated an infectious molecular clone of a pediatric clade C strain, HIV1084i, which was isolated from a Zambian infant infected either intrapartum or through breastfeeding. HIV1084i is an R5, non-syncytium-inducing isolate that bears all known clade C signatures; gag, pol, and env consistently mapped within clade C. Interestingly, gag resembled Asian isolates, whereas pol and env resembled African isolates, indicating that HIV1084i probably arose from an intraclade recombination. As a recently transmitted clade C strain, HIV1084i will be a useful vaccine development tool.

Amino Acid Sequence↗

Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence.

The evolution of dengue virus (DENV) is characterized by phylogenetic trees that have a strong temporal structure punctuated by dramatic changes in clade frequency. To determine the cause of these large-scale phylogenetic patterns, we examined the evolutionary history of DENV serotype 1 (DENV-1) and DENV-3 in Thailand, where gene sequence and epidemiological data are relatively abundant over a 30-year period. We found evidence for the turnover of viral clades in both serotypes, most notably in DENV-1, where a major clade replacement event took place in genotype I during the mid-1990s. Further, when this clade replacement event was placed in the context of changes in serotype prevalence in Thailand, a striking pattern emerged; an increase in DENV-1 clade diversity was associated with an increase in the abundance of this serotype and a concomitant decrease in DENV-4 prevalence, while clade replacement was associated with a decline in DENV-1 prevalence and a rise of DENV-4. We postulate that intraserotypic genetic diversification proceeds at times of relative serotype abundance and that replacement events can result from differential susceptibility to cross-reactive immune responses.

Dengue↗

Human immunodeficiency virus-specific responses in adult Ugandans: patterns of cross-clade recognition.

Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, with at least three HIV clades (subtypes) accounting for most new infections. Whether an effective vaccine formulated on viruses from a single clade will be able to protect against infection from other local clades remains unresolved. We examined the T-cell immune responses from a cohort of HIV-seropositive individuals in Uganda with predominantly clade A and D infections. Surprisingly, we observed similar frequencies of cross-clade T-cell responses to the gag, env, and nef regions. Our data suggest that the level of viral sequence variability between distinct HIV strains does not predict the degree of cross-clade responses. High sequence homologies were also observed between consensus peptides and sequences from viral isolates, supporting the use of consensus amino acid sequences to identify immunogenic regions in studies of large populations.

Adult↗

Phylogeny and taxonomy of the North American clade of the Ceratocystis fimbriata complex.

Ceratocystis fimbriata is a widely distributed, plant pathogenic fungus that causes wilts and cankers on many woody hosts. Earlier phylogenetic analyses of DNA sequences revealed three geographic clades within the C. fimbriata complex that are centered respectively in North America, Latin America and Asia. This study looked for cryptic species within the North American clade. The internal transcribed spacer regions (ITS) of the rDNA were sequenced, and phylogenetic analysis indicated that most isolates from the North American clade group into four host-associated lineages, referred to as the aspen, hickory, oak and cherry lineages, which were isolated primarily from wounds or diseased trees of Populus, Carya, Quercus and Prunus, respectively. A single isolate collected from P. serotina in Wisconsin had a unique ITS sequence. Allozyme electromorphs also were highly polymorphic within the North American clade, and the inferred phylogenies from these data were congruent with the ITS-rDNA analyses. In pairing experiments isolates from the aspen, hickory, oak and cherry lineages were interfertile only with other isolates from their respective lineages. Inoculation experiments with isolates of the four host-associated groupings showed strong host specialization by isolates from the aspen and hickory lineages on Populus tremuloides and Carya illinoensis, respectively, but isolates from the oak and cherry lineages did not consistently reveal host specialization. Morphological features distinguish isolates in the North American clade from those of the Latin American clade (including C. fimbriata sensu stricto). Based on the phylogenetic evidence, interfertility, host specialization and morphology, the oak and cherry lineages are recognized as the earlier described C. variospora, the poplar lineage as C. populicola sp. nov., and the hickory lineage as C. caryae sp. nov. A new species associated with the bark beetle Scolytus quadrispinosus on Carya is closely related to C. caryae and is described as C. smalleyi.

Ascomycota↗

Genealogical concordance between the mating type locus and seven other nuclear genes supports formal recognition of nine phylogenetically distinct species within the Fusarium graminearum clade.

Species limits were investigated within the Fusarium graminearum clade (Fg clade) through phylogenetic analyses of DNA sequences from portions of 11 nuclear genes including the mating-type (MAT) locus. Nine phylogenetically distinct species were resolved within the Fg clade, and they all possess contiguous MAT1-1 and MAT1-2 idiomorphs consistent with a homothallic reproductive mode. In contrast, only one of the two MAT idiomorphs was found in five other species, four of which were putatively asexual, and the other was heterothallic. Molecular evolutionary analyses indicate the MAT genes are under strong purifying selection and that they are functionally constrained, even in species for which a sexual state is unknown. The phylogeny supports a monophyletic and apomorphic origin of homothallism within this clade. Morphological analyses demonstrate that a combination of conidial characters could be used to differentiate three species and three species pairs. Species rank is formally proposed for the eight unnamed species within the Fg clade using fixed nucleotide characters.

Amino Acid Sequence↗

Comparative genomic analysis of the clade B serpin cluster at human chromosome 18q21: amplification within the mouse squamous cell carcinoma antigen gene locus.

The human clade B serpins neutralize serine or cysteine proteinases and reside predominantly within the intracellular compartment. Genomic analysis shows that the 13 human clade B serpins map to either 6p25 (n = 3) or 18q21 (n = 10). Similarly, the mouse clade B serpins map to syntenic loci at 13A3.2 and 1D, respectively. The mouse clade B cluster at 13A3.2 shows a marked expansion in the number of serpin genes (n = 15). The purpose of this study was to determine whether a similar expansion occurred at 1D. Using STS-content mapping, comparative genomic DNA sequence analysis, and cDNA cloning, we found that the mouse clade B cluster at 1D showed nearly complete conservation of gene number, order, and orientation relative to those of 18q21. The only exception was the squamous cell carcinoma antigen (SCCA) locus. The human SCCA locus contains two genes, SERPINB3 (SCCA1) and SERPINB4 (SCCA2), whereas the mouse locus contains four serpins and three pseudogenes. Based on phylogenetic analysis and predicted amino acid sequences, amplification of the mouse SCCA locus occurred after rodents and primates diverged and was associated with some diversification of proteinase inhibitory activity relative to that of humans.

Amino Acid Sequence↗

Phylogenetic significance of morphological characters in the tropical Hypotrachyna clade of parmelioid lichens (Parmeliaceae, Ascomycota).

Lichen-forming ascomycetes exhibit often complex morphologies of the vegetative thallus that are usually not found in non-lichenized fungi. This includes the thallus organization and appendical structures associated with the main thallus, such as cilia and rhizines. Such morphological characters are widely employed in the taxonomy of parmelioid lichens, especially at generic level. Within parmelioid lichens, several monophyletic groups can be distinguished, the Hypotrachyna clade being one of them, which includes mostly tropical taxa. In this first molecular study focused specifically on the Hypotrachyna clade, we used maximum parsimony and Bayesian analyses of a combined data set of nuclear ITS and mitochondrial SSU rDNA sequences to (1) test the monophyly of genera presently accepted within the clade and (2) evaluate the phylogenetic value of the morphological characters used to circumscribe genera in parmelioid lichens. Out of the 89 mtSSU and 88 nuITS sequences included in the present study, 121 sequences were newly obtained. Our results show that the taxa within the clade fall into two major groups and that the genus Hypotrachyna is polyphyletic. Everniastrum and Parmelinopsis are nested within Hypotrachyna sensu stricto, the latter being also polyphyletic. Bulbothrix is paraphyletic with Parmelinella nested within and is basal to the second major Hypotrachyna clade. Monophylies of Bulbothrix and Hypotrachyna are significantly rejected. The phylogenetic analysis demonstrates that morphological characters currently used to circumscribe genera in parmelioid lichens, such as cortical anatomy, lobe configuration, cilia, and rhizines have been overestimated and have only minor value in identifying monophyletic groups.

Lichens↗

Analysis of the mitochondrial 12S rRNA gene supports a two-clade hypothesis of the evolutionary history of scleractinian corals.

Scleractinian corals have long been assumed to be a monophyletic group characterized by the possession of an aragonite skeleton. Analyses of skeletal morphology and molecular data have shown conflicting patterns of suborder and family relationships of scleractinian corals, because molecular data suggest that the scleractinian skeleton could have evolved as many as four times. Here we describe patterns of molecular evolution in a segment of the mitochondrial (mt) 12S ribosomal RNA gene from 28 species of scleractinian corals and use this gene to infer the evolutionary history of scleractinians. We show that the sequences obtained fall into two distinct clades, defined by PCR product length. Base composition among taxa did not differ significantly when the two clades were considered separately or as a single group. Overall, transition substitutions accumulated more quickly relative to transversion substitutions within both clades. Spatial patterns of substitutions along the 12S rRNA gene and likelihood ratio tests of divergence rates both indicate that the 12S rRNA gene of each clade evolved under different constraints. Phylogenetic analyses using mt 12S rRNA gene data do not support the current view of scleractinian phylogeny based upon skeletal morphology and fossil records. Rather, the two-clade hypothesis derived from the mt 16S ribosomal gene is supported.

Animals↗

SAR11 clade dominates ocean surface bacterioplankton communities.

The most abundant class of bacterial ribosomal RNA genes detected in seawater DNA by gene cloning belongs to SAR11-an alpha-proteobacterial clade. Other than indications of their prevalence in seawater, little is known about these organisms. Here we report quantitative measurements of the cellular abundance of the SAR11 clade in northwestern Sargasso Sea waters to 3,000 m and in Oregon coastal surface waters. On average, the SAR11 clade accounts for a third of the cells present in surface waters and nearly a fifth of the cells present in the mesopelagic zone. In some regions, members of the SAR11 clade represent as much as 50% of the total surface microbial community and 25% of the subeuphotic microbial community. By extrapolation, we estimate that globally there are 2.4 x 10(28) SAR11 cells in the oceans, half of which are located in the euphotic zone. Although the biogeochemical role of the SAR11 clade remains uncertain, these data support the conclusion that this microbial group is among the most successful organisms on Earth.

Alphaproteobacteria↗