School of BioSciences - Research Publications
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ItemNo Preview AvailableEvolution of pathogenicity and sexual reproduction in eight Candida genomes.(Springer Science and Business Media LLC, 2009-06-04)Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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ItemNo Preview AvailableEvolving proteins at Darwin's bicentenary.(Springer Science and Business Media LLC, 2009)A report of the Biochemical Society/Wellcome Trust meeting 'Protein Evolution - Sequences, Structures and Systems', Hinxton, UK, 26-27 January 2009.
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ItemNo Preview AvailableHelpers and egg investment in the cooperatively breeding acorn woodpecker: testing the concealed helper effects hypothesis(SPRINGER, 2009-09-01)In cooperatively breeding acorn woodpeckers (Melanerpes formicivorus), helper males have a large positive effect on fledging success in good acorn crop years but only a small positive effect in poor acorn crop years, while helper females exhibit the opposite pattern. Based on these findings, we tested the "concealed helper effects" hypothesis, which proposes that laying females reduce investment in eggs (with respect to their size, number, or quality) in a way that confounds helper effects and results in an absence of a relationship between helpers and breeding success. Results generally failed to support the hypothesis. Mean egg size was positively related to temperatures during the 10 days prior to egg-laying and negatively related to the food supply as indexed by the prior fall's acorn crop, but there were no significant differences vis-à-vis helpers except for interactions with the acorn crop that only partly corresponded to those predicted. With respect to clutch size, females laid larger clutches when assisted by female helpers, opposite the pattern predicted. Although our results suggest that egg size is adjusted to particular ecological circumstances, we conclude that neither egg nor clutch size is adjusted in a way that confounds the apparent effects of helpers, as proposed by the concealed helper effects hypothesis.
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ItemNo Preview AvailableBirth and Death of Genes and Functions in the beta-Esterase Cluster of Drosophila(SPRINGER, 2009-07-01)Here we analyze the molecular evolution of the beta-esterase gene cluster in the Drosophila genus using the recently released genome sequences of 12 Drosophila species. Molecular evolution in this small cluster is noteworthy because it contains contrasting examples of the types and stages of loss of gene function. Specifically, missing orthologs, pseudogenes, and null alleles are all inferred. Phylogenetic analyses also suggest a minimum of 9 gene gain-loss events; however, the exact number and age of these events is confounded by interparalog recombination. A previous enigma, in which allozyme loci were mapped to beta-esterase genes that lacked catalytically essential amino acids, was resolved through the identification of neighbouring genes that contain the canonical catalytic residues and thus presumably encode the mapped allozymes. The originally identified genes are evolving with selective constraint, suggesting that they have a "noncatalytic" function. Curiously, 3 of the 4 paralogous beta-esterase genes in the D. ananassae genome sequence have single inactivating (frame-shift or nonsense) mutations. To determine whether these putatively inactivating mutations were fixed, we sequenced other D. ananassae alleles of these four loci. We did not find any of the 3 inactivating mutations of the sequenced strain in 12 other strains; however, other inactivating mutations were observed in the same 3 genes. This is reminiscent of the high frequency of null alleles observed in one of the beta-esterase genes (Est7/EstP) of D. melanogaster.
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ItemGain and loss of elongation factor genes in green algae(BIOMED CENTRAL LTD, 2009-02-12)BACKGROUND: Two key genes of the translational apparatus, elongation factor-1 alpha (EF-1alpha) and elongation factor-like (EFL) have an almost mutually exclusive distribution in eukaryotes. In the green plant lineage, the Chlorophyta encode EFL except Acetabularia where EF-1alpha is found, and the Streptophyta possess EF-1alpha except Mesostigma, which has EFL. These results raise questions about evolutionary patterns of gain and loss of EF-1alpha and EFL. A previous study launched the hypothesis that EF-1alpha was the primitive state and that EFL was gained once in the ancestor of the green plants, followed by differential loss of EF-1alpha or EFL in the principal clades of the Viridiplantae. In order to gain more insight in the distribution of EF-1alpha and EFL in green plants and test this hypothesis we screened the presence of the genes in a large sample of green algae and analyzed their gain-loss dynamics in a maximum likelihood framework using continuous-time Markov models. RESULTS: Within the Chlorophyta, EF-1alpha is shown to be present in three ulvophycean orders (i.e., Dasycladales, Bryopsidales, Siphonocladales) and the genus Ignatius. Models describing gene gain-loss dynamics revealed that the presence of EF-1alpha, EFL or both genes along the backbone of the green plant phylogeny is highly uncertain due to sensitivity to branch lengths and lack of prior knowledge about ancestral states or rates of gene gain and loss. Model refinements based on insights gained from the EF-1alpha phylogeny reduce uncertainty but still imply several equally likely possibilities: a primitive EF-1alpha state with multiple independent EFL gains or coexistence of both genes in the ancestor of the Viridiplantae or Chlorophyta followed by differential loss of one or the other gene in the various lineages. CONCLUSION: EF-1alpha is much more common among green algae than previously thought. The mutually exclusive distribution of EF-1alpha and EFL is confirmed in a large sample of green plants. Hypotheses about the gain-loss dynamics of elongation factor genes are hard to test analytically due to a relatively flat likelihood surface, even if prior knowledge is incorporated. Phylogenetic analysis of EFL genes indicates misinterpretations in the recent literature due to uncertainty regarding the root position.
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ItemRadical loss of an extreme extra-pair mating system.(Springer Science and Business Media LLC, 2009-05-19)BACKGROUND: Mating outside the pair-bond is surprisingly common in socially monogamous birds, but rates of extra-pair paternity (EPP) vary widely between species. Although differences in life-history and contemporary ecological factors may explain some interspecific variation, evolutionary forces driving extra-pair (EP) mating remain largely obscure. Also, since there is a large phylogenetic component to the frequency of EPP, evolutionary inertia may contribute substantially to observed EP mating patterns. However, the relative importance of plasticity and phylogenetic constraints on the incidence of EP mating remains largely unknown. RESULTS: We here demonstrate very low levels of EPP (4.4% of offspring) in the purple-crowned fairy-wren Malurus coronatus, a member of the genus with the highest known levels of EPP in birds. In addition, we show absence of the suite of distinctive behavioral and morphological adaptations associated with EP mating that characterize other fairy-wrens. Phylogenetic parsimony implies that these characteristics were lost in one speciation event. Nonetheless, many life-history and breeding parameters that are hypothesized to drive interspecific variation in EPP are not different in the purple-crowned fairy-wren compared to its promiscuous congeners. CONCLUSION: Such radical loss of an extreme EP mating system with all associated adaptations from a lineage of biologically very similar species indicates that evolutionary inertia does not necessarily constrain interspecific variation in EPP. Moreover, if apparently minor interspecific differences regularly cause large differences in EPP, this may be one reason why the evolution of EP mating is still poorly understood.
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ItemIn Vivo Yeast Cell Morphogenesis Is Regulated by a p21-Activated Kinase in the Human Pathogen Penicillium marneffei(PUBLIC LIBRARY SCIENCE, 2009-11-01)Pathogens have developed diverse strategies to infect their hosts and evade the host defense systems. Many pathogens reside within host phagocytic cells, thus evading much of the host immune system. For dimorphic fungal pathogens which grow in a multicellular hyphal form, a central attribute which facilitates growth inside host cells without rapid killing is the capacity to switch from the hyphal growth form to a unicellular yeast form. Blocking this transition abolishes or severely reduces pathogenicity. Host body temperature (37 degrees C) is the most common inducer of the hyphal to yeast transition in vitro for many dimorphic fungi, and it is often assumed that this is the inducer in vivo. This work describes the identification and analysis of a new pathway involved in sensing the environment inside a host cell by a dimorphic fungal pathogen, Penicillium marneffei. The pakB gene, encoding a p21-activated kinase, defines this pathway and operates independently of known effectors in P. marneffei. Expression of pakB is upregulated in P. marneffei yeast cells isolated from macrophages but absent from in vitro cultured yeast cells produced at 37 degrees C. Deletion of pakB leads to a failure to produce yeast cells inside macrophages but no effect in vitro at 37 degrees C. Loss of pakB also leads to the inappropriate production of yeast cells at 25 degrees C in vitro, and the mechanism underlying this requires the activity of the central regulator of asexual development. The data shows that this new pathway is central to eliciting the appropriate morphogenetic response by the pathogen to the host environment independently of the common temperature signal, thus clearly separating the temperature- and intracellular-dependent signaling systems.
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ItemComparative analysis of the mammalian WNT4 promoter(BMC, 2009-09-06)BACKGROUND: WNT4 is a critical signalling molecule in embryogenesis and homeostasis, but the elements that control its transcriptional regulation are largely unknown. This study uses comparative cross species sequence and functional analyses between humans and a marsupial (the tammar wallaby,Macropus eugenii) to refine the mammalian Wnt4 promoter. RESULTS: We have defined a highly conserved 89 bp minimal promoter region in human WNT4 by comparative analysis with the tammar wallaby. There are many conserved transcription factor binding sites in the proximal promoter region, including SP1, MyoD, NFkappaB and AP2, as well as highly conserved CpG islands within the human, mouse and marsupial promoters, suggesting that DNA methylation may play an important role in WNT4 transcriptional regulation. CONCLUSION: Using a marsupial model, we have been able to provide new information on the transcriptional regulators in the promoter of this essential mammalian developmental gene, WNT4. These transcription factor binding sites and CpG islands are highly conserved in two disparate mammals, and are likely key controlling elements in the regulation of this essential developmental gene.
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ItemThe Photobiology of Microbial Pathogenesis(PUBLIC LIBRARY SCIENCE, 2009-11-01)
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ItemGenomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication(PUBLIC LIBRARY SCIENCE, 2009-07-01)Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called "zygomycetes," R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99-880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin-proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families, which are known fungal virulence factors. The duplication of the ergosterol biosynthetic pathway, especially the major azole target, lanosterol 14alpha-demethylase (ERG11), could contribute to the variable responses of R. oryzae to different azole drugs, including voriconazole and posaconazole. Expanded families of cell-wall synthesis enzymes, essential for fungal cell integrity but absent in mammalian hosts, reveal potential targets for novel and R. oryzae-specific diagnostic and therapeutic treatments.