Browsing by Author "Holland BR"

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    Impact of genetic background on allele selection in a highly mutable Candida albicans gene, PNG2
    (PLoS ONE, 2010) Zhang N; Cannon RD; Holland BR; Patchett ML; Schmid J
    In many microbes rapid mutation of highly mutable contingency genes continually replenishes a pool of variant alleles from which the most suitable are selected, assisting in rapid adaptation and evasion of the immune response. In some contingency genes mutability is achieved through DNA repeats within the coding region. The fungal human pathogen Candida albicans has 2600 repeat-containing ORFs. For those investigated (ALS genes, HYR1, HYR2, CEK1, RLM1) many protein variants with differing amino acid repeat regions exist, as expected for contingency genes. However, specific alleles dominate in different clades, which is unexpected if allele variation is used for short-term adaptation. Generation of new alleles of repeat-containing C. albicans ORFs has never been observed directly. Here we present evidence for restrictions on the emergence of new alleles in a highly mutable C. albicans repeat-containing ORF, PNG2, encoding a putative secreted or cell surface glycoamidase. In laboratory cultures new PNG2 alleles arose at a rate of 2.8x10(-5) (confidence interval 3.3x10(-6)-9. 9x10(-5)) per cell per division, comparable to rates measured for contingency genes. Among 80 clinical isolates 17 alleles of different length and 23 allele combinations were distinguishable; sequence differences between repeat regions of identical size suggest the existence of 36 protein variants. Specific allele combinations predominated in different genetic backgrounds, as defined by DNA fingerprinting and multilocus sequence typing. Given the PNG2 mutation rate, this is unexpected, unless in different genetic backgrounds selection favors different alleles. Specific alleles or allele combinations were not preferentially associated with C. albicans isolates from particular body sites or geographical regions. Our results suggest that the mutability of PNG2 is not used for short-term adaptation or evasion of the immune system. Nevertheless the large number of alleles observed indicates that mutability of PNG2 may assist C. albicans strains from different genetic backgrounds optimize their interaction with the host in the long term.
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    Using supernetworks to distinguish hybridization from lineage-sorting
    (BioMed Central, 2008) Holland BR; Benthin S; Lockhart PJ; Moulton V; Huber KT
    BackgroundA simple and widely used approach for detecting hybridization in phylogenies is to reconstruct gene trees from independent gene loci, and to look for gene tree incongruence. However, this approach may be confounded by factors such as poor taxon-sampling and/or incomplete lineage-sorting.ResultsUsing coalescent simulations, we investigated the potential of supernetwork methods to differentiate between gene tree incongruence arising from taxon sampling and incomplete lineage-sorting as opposed to hybridization. For few hybridization events, a large number of independent loci, and well-sampled taxa across these loci, we found that it was possible to distinguish incomplete lineage-sorting from hybridization using the filtered Z-closure and Q-imputation supernetwork methods. Moreover, we found that the choice of supernetwork method was less important than the choice of filtering, and that count-based filtering was the most effective filtering technique.ConclusionFiltered supernetworks provide a tool for detecting and identifying hybridization events in phylogenies, a tool that should become increasingly useful in light of current genome sequencing initiatives and the ease with which large numbers of independent gene loci can be determined using new generation sequencing technologies.