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  1. Home
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Browsing by Subject "Natural selection"

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    Characterizing the Evolutionary Path(s) to Early Homo
    (Public Library of Science, 2014) Schroeder, Lauren; Roseman, Charles C.; Cheverud, James M.; Ackermann, Rebecca Rogers
    Numerous studies suggest that the transition from Australopithecus to Homo was characterized by evolutionary innovation, resulting in the emergence and coexistence of a diversity of forms. However, the evolutionary processes necessary to drive such a transition have not been examined. Here, we apply statistical tests developed from quantitative evolutionary theory to assess whether morphological differences among late australopith and early Homo species in Africa have been shaped by natural selection. Where selection is demonstrated, we identify aspects of morphology that were most likely under selective pressure, and determine the nature (type, rate) of that selection. Results demonstrate that selection must be invoked to explain an Au. africanus -- Au. sediba -- Homo transition, while transitions from late australopiths to various early Homo species that exclude Au. sediba can be achieved through drift alone. Rate tests indicate that selection is largely directional, acting to rapidly differentiate these taxa. Reconstructions of patterns of directional selection needed to drive the Au. africanus -- Au. sediba -- Homo transition suggest that selection would have affected all regions of the skull. These results may indicate that an evolutionary path to Homo without Au. sediba is the simpler path and/or provide evidence that this pathway involved more reliance on cultural adaptations to cope with environmental change.
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    Frequent toggling between alternative amino acids is driven by selection in HIV-1
    (Public Library of Science, 2008) Delport, Wayne; Scheffler, Konrad; Seoighe, Cathal
    Author Summary Viruses, such as HIV, are able to evade host immune responses through escape mutations, yet sometimes they do so at a cost. This cost is the reduction in the ability of the virus to replicate, and thus selective pressure exists for a virus to revert to its original state in the absence of the host immune response that caused the initial escape mutation. This pattern of escape and reversion typically occurs when viruses are transmitted between individuals with different immune responses. We develop a phylogenetic model of immune escape and reversion and provide evidence that it outperforms existing models for the detection of selective pressure associated with host immune responses. Finally, we demonstrate that amino acid toggling is a pervasive process in HIV-1 evolution, such that many of the positions in the virus that evolve rapidly, under the influence of positive Darwinian selection, nonetheless display quite low sequence diversity. This highlights the limitations of HIV-1 evolution, and sites such as these are potentially good targets for HIV-1 vaccines.
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    Genetic signatures for enhanced olfaction in the African mole-rats
    (Public Library of Science, 2014) Stathopoulos, Sofia; Bishop, Jacqueline M; O'Ryan, Colleen
    The Olfactory Receptor (OR) superfamily, the largest in the vertebrate genome, is responsible for vertebrate olfaction and is traditionally subdivided into 17 OR families. Recent studies characterising whole-OR subgenomes revealed a ‘birth and death’ model of evolution for a range of species, however little is known about fine-scale evolutionary dynamics within single-OR families. This study reports the first assessment of fine-scale OR evolution and variation in African mole-rats (Bathyergidae), a family of subterranean rodents endemic to sub-Saharan Africa. Because of the selective pressures of life underground, enhanced olfaction is proposed to be fundamental to the evolutionary success of the Bathyergidae, resulting in a highly diversified OR gene-repertoire. Using a PCR-sequencing approach, we analysed variation in the OR7 family across 14 extant bathyergid species, which revealed enhanced levels of functional polymorphisms concentrated across the receptors’ ligand-binding region. We propose that mole-rats are able to recognise a broad range of odorants and that this diversity is reflected throughout their OR7 gene repertoire. Using both classic tests and tree-based methods to test for signals of selection, we investigate evolutionary forces across the mole-rat OR7 gene tree. Four well-supported clades emerged in the OR phylogeny, with varying signals of selection; from neutrality to positive and purifying selection. Bathyergid life-history traits and environmental niche-specialisation are explored as possible drivers of adaptive OR evolution, emerging as non-exclusive contributors to the positive selection observed at OR7 genes. Our results reveal unexpected complexity of evolutionary mechanisms acting within a single OR family, providing insightful perspectives into OR evolutionary dynamics.
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    HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC
    (Public Library of Science, 2009) Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F; McMichael, Andrew
    Author Summary HIV is a rapidly evolving virus, displaying enormous genetic diversity between and even within infected individuals, with implications for vaccine design and drug treatment. Yet, recent research has shown that most new infections result from transmission of a single virus resulting in a homogeneous viral population in early infection. The process of diversification from the transmitted virus provides information about the selection pressures experienced by the virus during the establishment of a new infection. In this paper, we studied early diversification of the envelope gene in a cohort of 81 subjects acutely infected with HIV-1 subtype B and found evidence of adaptive evolution, with a proportion of sites that tended to diversify more rapidly than expected under a model of neutral evolution. Several of these rapidly diversifying sites facilitate escape from early cytotoxic immune responses. Interestingly, hypermutation of the virus, brought about by host proteins as a strategy to restrict infection, appeared to be associated with early immune escape. In addition to single base substitutions, insertions and deletions are an important aspect of HIV evolution. We show that insertion and deletion mutations occur evenly across the gene, but are preferentially fixed in the variable loop regions.
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    No evidence for selection of HIV-1 with enhanced Gag-Protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial
    (Public Library of Science, 2013) Chopera, Denis R; Mann, Jaclyn K; Mwimanzi, Philip; Omarjee, Saleha; Kuang, Xiaomei T; Ndabambi, Nonkululeko; Goodier, Sarah; Martin, Eric; Naranbhai, Vivek; Karim, Salim Abdool
    BACKGROUND: Use of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial. Methods and RESULTS: We isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein downregulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis. CONCLUSION: Results indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness.
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