- Email: [email protected]
Wolbachia Genomes: Insights into an Intracellular Lifestyle
Dispatch R507
elongation in Drosophila, epithelial cells intercalate and change position via an ordered process of cell contact remodelling, whereby a set of junctions are lost while another set of junctions is re-established [17]. The loss of cell contacts at adherens junctions can be described in terms of polarized down-regulation of adhesion. Yet, the process may also reflect polarized cortical tension at adherens junctions. This is supported by the fact that myosin-II is enriched in shrinking junctions and could locally constrict the cell in a subset of junctions [17,18]. It becomes clearer that it is necessary to develop ways to directly measure in vivo intercellular adhesion and cortical cell tension to distinguish their respective contribution in cell and tissue morphogenesis.
4.
5.
6.
7.
8.
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References 1. Knust, E., and Bossinger, O. (2002). Composition and formation of intercellular junctions in epithelial cells. Science 298, 1955–1959. 2. Nelson, W.J. (2003). Adaptation of core mechanisms to generate cell polarity. Nature 422, 766–774. 3. Lecuit, T. (2005). Adhesion remodelling underlying patterned cell shape and
12.
13.
tissue morphogenesis. Trends Cell Biol. 15, 34–42. Townes, P., and Holtfreter, J. (1955). Directed movements and selective adhesion of embryonic cells. J. Exp. Zool. 128, 53–118. Steinberg, M.S., and Takeichi, M. (1994). Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression. Proc. Natl. Acad. Sci. USA 91, 206–209. Steinberg, M.S. (1996). Adhesion in development: an historical overview. Dev. Biol. 180, 377–388. Duguay, D., Foty, R.A., and Steinberg, M.S. (2003). Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev. Biol. 253, 309–323. Hayashi, T., and Carthew, R. (2004). Surface mechanics mediate pattern formation in the developing retina. Nature 431, 647–652. Garcia-Bellido, A., Ripoll, P., and Morata, G. (1973). Developmental compartmentalisation of the wing disk of Drosophila. Nat. New Biol. 245, 251–253. Morata, G., and Lawrence, P.A. (1975). Control of compartment development by the engrailed gene in Drosophila. Nature 255, 614–617. Dahmann, C., and Basler, K. (2000). Opposing transcriptional outputs of Hedgehog signaling and engrailed control compartmental cell sorting at the Drosophila A/P boundary. Cell 100, 411–422. Wei, S.Y., Escudero, L.M., Yu, F., Chang, L.H., Chen, L.Y., Ho, Y.H., Lin, C.M., Chou, C.S., Chia, W., Modolell, J. et al. (2005). Echinoid is a component of adherens junctions that cooperates with DE-Cadherin to mediate cell adhesion. Dev. Cell 8, 493–504. Escudero, L.M., Wei, S.Y., Chiu, W.H.,
Wolbachia Genomes: Insights into an Intracellular Lifestyle The genome sequence of the Wolbachia endosymbiont that infects the nematode Brugia malayi has recently been determined together with three partial Wolbachia genomes from different Drosophila species. These data along with the previously published Wolbachia genome from Drosophila melanogaster provide new insights into how this endosymbiont has managed to become so successful. Jeremy C. Brownlie and Scott L. O’Neill* Wolbachia pipientis is a maternally inherited, intracellular bacterium estimated to infect more than 20% of all insect species as well as a range of other invertebrates, including mites, spiders, crustaceans and nematodes. W. pipientis has profound effects on its hosts, ranging from conventional mutualism where it increases host fitness, to reproductive
parasitism. In the latter case, it induces for instance cytoplasmic incompatibility, parthenogenesis, feminization and male-killing [1]. All of the described Wolbachia induced phenotypes benefit the bacterium by enhancing its vertical transmission into host populations. The publication of the sequences of a number of Wolbachia genomes within the last year provides new insights into the biology of this fascinating group of microorganisms. This is especially the case when the
14.
15.
16.
17.
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Modolell, J., and Hsu, J.C. (2003). Echinoid synergizes with the Notch signaling pathway in Drosophila mesothorax bristle patterning. Development 130, 6305–6316. Ahmed, A., Chandra, S., Magarinos, M., and Vaessin, H. (2003). Echinoid mutants exhibit neurogenic phenotypes and show synergistic interactions with the Notch signaling pathway. Development 130, 6295–6304. Rawlins, E.L., White, N.M., and Jarman, A.P. (2003). Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups. Development 130, 3715–3724. Bai, J., Chiu, W., Wang, J., Tzeng, T., Perrimon, N., and Hsu, J. (2001). The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway. Development 128, 591–601. Bertet, C., Sulak, L., and Lecuit, T. (2004). Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671. Zallen, J.A., and Wieschaus, E. (2004). Patterned gene expression directs bipolar planar polarity in Drosophila. Dev. Cell 6, 343–355.
Laboratoire de Génétique et de Physiologie du Développement (LGPD), UMR 6545, CNRS-Université de la Méditerrannée, Institut de Biologie du Développement de Marseille (IBDM), Campus de Luminy, case 907, 13288 Marseille cedex 09, France. E-mail: [email protected] DOI: 10.1016/j.cub.2005.06.028
genome sequences of different Wolbachia strains are compared, such as the parasitic Drosophila symbiont wMel [2] and its mutualistic relative wBm [3] which infects the nematode Brugia malayi, a causal agent of filariasis. Repetitive DNA and Genomic Plasticity One of the most striking features of the first Wolbachia genome sequence from the strain wMel was the large amount of repetitive DNA. Like other intracellular bacteria, the size of Wolbachia’s genome is considerably smaller than that of its free living relatives [4]. Despite this obvious streamlining, at least 14% of the wMel genome is composed of numerous repetitive DNA sequences and insertions. These repetitive elements have significantly influenced the genome organisation of wMel by providing sites for recombination
Current Biology Vol 15 No 13 R508
and rearrangements. As a result, there is little colinearity between the genome of the wMel strain and the genome of the related, nematode infecting strain wBm [3]. Unlike Wolbachia that infect insects and display reproductive parasitism traits, filarial nematode Wolbachia are obligate mutualists. They share similarities to other obligate mutualists (e.g. the Buchnera symbionts of aphids) such as concordant phylogenies with their hosts (indicating lack of horizontal transmission) and greatly reduced genome size [3–5]. In contrast, Wolbachia that induce reproductive parasitism traits have considerably larger genomes [2,6], and show phylogenetic evidence of horizontal transfer [7,8]. Compared to wMel, the genome of wBm lacks repetitive DNA and prophage sequences [3]. Considering that repetitive DNA is also absent from the genomes of other mutualistic intracellular symbionts [4], the presence of such a large amount of repetitive sequences in parasitic Wolbachia, like wMel raises the question of its potential adaptive significance [3]. The abundance of repetitive DNA in wMel-like genomes is expected to confer increased plasticity by providing sites for genome shuffling. Such shuffling events are likely to vary gene expression, by interrupting promoter or termination sequences, or by the duplication or deletion of individual genes. Similarly, the potential of phages to transfer genetic material among parasitic Wolbachia strains may help to increase plasticity. This capability may be actively selected as a mechanism that facilitates successful establishment of parasitic Wolbachia within novel host lineages after horizontal transmission. It may also explain the increased phenotypic variability among parasitic Wolbachia strains. Towards a Functional Understanding While the genome sequences of the two strains do not reveal the molecular basis of the various phenotypes that Wolbachia can
induce, they do point towards some potential mechanisms. For example, when considering how Wolbachia might act as a mutualist in the nematode, the genome sequences clearly demonstrate that this cannot be due to the production of amino acids for the host, as is the case in a number of other mutualistic associations [9–11]. Like other Wolbachia strains, wBm appears unable to synthesize a range of amino acids, carbohydrates or essential lipids and presumably acquires these from its host [3]. Interestingly, analysis of the wBm and B. malayi genomes has revealed that both contain incomplete pathways for the synthesis of various coenzymes and cofactors. When both genomes are combined, however, these pathways appear complete [3]. Rather than providing amino acids, wBm appears to be supplying two essential cofactors, riboflavin and heme, to the nematode host [3]. Thus, when Wolbachia are purged from their filarial nematode hosts, the nematodes may be effectively starved of heme and riboflavin, which disrupts proper molting and fecundity. Given these findings, it seems likely that the disruption of this symbiosis will continue to be a focus of research aimed at developing novel filariasis control strategies [12]. While a clear link between Wolbachia derived cofactors and the nematode host can be established, it is less clear which benefit Wolbachia might provide to its insect host? It is known that some Wolbachia that have been largely considered reproductive parasites are also at times capable of positively influencing host fitness [13,14]. It is known that insects suffer from retarded larval development and increased mortality in vitamin deficient environments [15] and that some obligate insect symbionts provision their hosts with vitamins [10]. If Wolbachia are capable of providing additional sources of riboflavin to their developing insect hosts, this could provide a selective advantage in nutritionally deficient or fluctuating environments. It will be of interest
to determine whether Wolbachia can deliver these additional cofactors to insect hosts and whether they may form the basis of the positive effects on fitness in insects. At present, there is great interest in unraveling the molecular basis of the various Wolbachia mediated reproductive parasitism traits that occur in insects. The initial wMel genome sequence identified an exceptionally large number of genes coding for proteins with ankyrin repeat domains. These proteins have many of the characteristics of proteins that might be playing a significant role in the maintenance of symbiosis as well as in the reproductive phenotypes [2,16]. Consistent with this hypothesis is the observation of a very reduced set of ankyrin domain proteins in the wBm genome. Since nematode Wolbachia are not known to reproductively manipulate their hosts, it would be expected that their genomes lack the genes for this capability. Hidden Genomes Another exciting development in Wolbachia research has been the unexpected discovery of a number of partial Wolbachia genomes that have been sequenced as a by-product of other insect genome sequencing projects. These sequences have been lying unnoticed in the trace archives. By mining trace archives, Salzberg and colleagues [17] have reported the recovery of three partial genomes of Wolbachia strains that infect different Drosophila species. This approach could potentially reveal a rich source of new Wolbachia genomic information. However, some caution needs to be taken with these data, as it is possible that the low coverage may result in a number of sequencing errors as well as the possibility of chimeric assemblies from multiple co-infecting symbiont genomes. Despite these limitations, it is very exciting that numerous additional Wolbachia genomes may be potentially sequenced in the course of ongoing and future insect genome projects. These
Dispatch R509
data will further accelerate our understanding of the biology of Wolbachia. References 1. O’Neill, S.L., Hoffmann, A.A., and Werren, J.H. (1997). Influential Passengers. Inherited Microorganisms and Arthropod Reproduction (Oxford: Oxford University Press). 2. Wu, M., Sun, L.V., Vamathevan, J., Riegler, M., Deboy, R., Brownlie, J.C., McGraw, E.A., Martin, W., Esser, C., Ahmadinejad, N., et al. (2004). Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. PLoS Biol. 2, E69. 3. Foster, J., Ganatra, M., Kamal, I., Ware, J., Makarova, K., Ivanova, N., Bhattacharyya, A., Kapatral, V., Kumar, S., Posfai, J., et al. (2005). The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. PLoS Biol. 3, E121. 4. Wernegreen, J.J. (2002). Genome evolution in bacterial endosymbionts of insects. Nat. Rev. Genet. 3, 850–861. 5. Andersson, J.O., and Andersson, S.G. (1999). Genome degradation is an ongoing process in Rickettsia. Mol. Biol. Evol. 16, 1178–1191. 6. Sun, L.V., Foster, J.M., Tzertzinis, G., Ono, M., Bandi, C., Slatko, B.E., and O’Neill, S.L. (2001). Determination of
Wolbachia genome size by pulsed-field gel electrophoresis. J. Bacteriol. 183, 2219–2225. 7. Werren, J.H., Zhang, W., and Guo, L.R. (1995). Evolution and phylogeny of Wolbachia: reproductive parasites of arthropods. Proc. Biol. Sci. 261, 55–63. 8. O’Neill, S.L., Giordano, R., Colbert, A.M., Karr, T.L., and Robertson, H.M. (1992). 16S rRNA phylogenetic analysis of the bacterial endosymbionts associated with cytoplasmic incompatibility in insects. Proc. Natl. Acad. Sci. USA 89, 2699–2702. 9. Baumann, P., Baumann, L., Lai, C.Y., Rouhbakhsh, D., Moran, N.A., and Clark, M.A. (1995). Genetics, physiology, and evolutionary relationships of the genus Buchnera: intracellular symbionts of aphids. Annu. Rev. Microbiol. 49, 55–94. 10. Akman, L., Yamashita, A., Watanabe, H., Oshima, K., Shiba, T., Hattori, M., and Aksoy, S. (2002). Genome sequence of the endocellular obligate symbiont of tsetse flies, Wigglesworthia glossinidia. Nat. Genet. 32, 402–407. 11. Gil, R., Silva, F.J., Zientz, E., Delmotte, F., Gonzalez-Candelas, F., Latorre, A., Rausell, C., Kamerbeek, J., Gadau, J., Holldobler, B., et al. (2003). The genome sequence of Blochmannia floridanus: comparative analysis of reduced genomes. Proc. Natl. Acad. Sci. USA 100, 9388–9393. 12. Taylor, M.J., and Hoerauf, A. (2001). A new approach to the treatment of
Fungal Genomics: Forensic Evidence of Sexual Activity The genome sequence of the ‘asexual’ human pathogenic fungus Aspergillus fumigatus suggests it has the capability to undergo mating and meiosis. That this organism engages in clandestine sexual activity is also suggested by observations of two equally distributed complementary mating types in nature, the expression of mating type genes and evidence of recent genome recombination events. Neil A.R. Gow The completion of the genome sequences of three Aspergillus species provides a resource to explore new avenues of fungal biology and evolution. Three genome centres — the Institute for Genome Research (TIGR), The Wellcome Sanger Genome Centre and The National Institute of Technology and Evaluation (NITE) in Japan — have collaborated with three rather separate scientific communities to sequence and annotate the genomes of three filamentous fungi with contrasting claims to fame. Aspergillus nidulans has a long tradition as a model eukaryote, and was the organism in which many basic findings
about growth and nuclear division were discovered; A. oryzae is an important fungus in industrial fermentation of sake, soy sauce and miso; and A. fumigatus is infamous as a pernicious pathogen of the immunocompromised. On the heels of the publication of the Aspergillus genome sequences comes an important new biological advance, reported in this issue of Current Biology: Dyer and colleagues [1] have used the sequence of A. fumigatus to obtain evidence that this fungus, traditionally classified amongst the asexual or so-called ‘imperfect’ fungi, may have been holding back the truth about its sexuality. Rather than being asexual, it seems to have the
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filariasis. Curr. Opin. Infect. Dis. 14, 727–731. Fry, A.J., Palmer, M.R., and Rand, D.M. (2004). Variable fitness effects of Wolbachia infection in Drosophila melanogaster. Heredity 93, 379–389. Dobson, S.L., Rattanadechakul, W., and Marsland, E.J. (2004). Fitness advantage and cytoplasmic incompatibility in Wolbachia single- and superinfected Aedes albopictus. Heredity 93, 135–142. Bruins, B.G., Scharloo, W., and Thorig, G.E. (1997). Light-induced vitamin deficiency in Drosophila melanogaster. Arch. Insect Biochem. Physiol. 36, 51–67. Iturbe-Ormaetxe, I., Burke, G.R., Riegler, M., and O’Neill, S.L. (2005). Distribution, gene expression and motif variability of ankyrin domain genes in Wolbachia pipientis. J. Bacteriol., in press. DOI: 10.1128/jb.187.15.000-000.2 Salzberg, S.L., Hotopp, J.C., Delcher, A.L., Pop, M., Smith, D.R., Eisen, M.B., and Nelson, W.C. (2005). Serendipitous discovery of Wolbachia genomes in multiple Drosophila species. Genome Biol. 6, R23.
School of Integrative Biology, University of Queensland, Brisbane, Qld 4072, Australia. *E-mail: [email protected] DOI: 10.1016/j.cub.2005.06.029
genetic machinery to mate, develop a sexual fruiting body and undergo a full meiotic cycle. The significance of this relates to the importance of A. fumigatus as a pathogen and difficulties in its genetic analysis. It is appropriate for this fungus to be named after its ability to produce a smoke trail, or fumus, of conidial spores, as these are the agents of infection and route of infection into the lung. The fungus is a common mould of compost and plant surfaces and it is estimated that a cubic metre of air contains 1-10 conidia, which most people will inhale with no ill effect [2]. But in the immunocompromised patient, who lacks the normally efficient surveillance of pulmonary macrophages and circulating monocytes and neutrophils, the spores germinate. The ensuing invasive filamentous growth in the lung and other body sites results in a disease which 80–90% of patients will not survive, even with best available antifungal treatments [3,4]. The severity of systemic aspergillosis has fuelled efforts to understand the nature of the virulence traits of this pathogen
elongation in Drosophila, epithelial cells intercalate and change position via an ordered process of cell contact remodelling, whereby a set of junctions are lost while another set of junctions is re-established [17]. The loss of cell contacts at adherens junctions can be described in terms of polarized down-regulation of adhesion. Yet, the process may also reflect polarized cortical tension at adherens junctions. This is supported by the fact that myosin-II is enriched in shrinking junctions and could locally constrict the cell in a subset of junctions [17,18]. It becomes clearer that it is necessary to develop ways to directly measure in vivo intercellular adhesion and cortical cell tension to distinguish their respective contribution in cell and tissue morphogenesis.
4.
5.
6.
7.
8.
9.
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References 1. Knust, E., and Bossinger, O. (2002). Composition and formation of intercellular junctions in epithelial cells. Science 298, 1955–1959. 2. Nelson, W.J. (2003). Adaptation of core mechanisms to generate cell polarity. Nature 422, 766–774. 3. Lecuit, T. (2005). Adhesion remodelling underlying patterned cell shape and
12.
13.
tissue morphogenesis. Trends Cell Biol. 15, 34–42. Townes, P., and Holtfreter, J. (1955). Directed movements and selective adhesion of embryonic cells. J. Exp. Zool. 128, 53–118. Steinberg, M.S., and Takeichi, M. (1994). Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression. Proc. Natl. Acad. Sci. USA 91, 206–209. Steinberg, M.S. (1996). Adhesion in development: an historical overview. Dev. Biol. 180, 377–388. Duguay, D., Foty, R.A., and Steinberg, M.S. (2003). Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev. Biol. 253, 309–323. Hayashi, T., and Carthew, R. (2004). Surface mechanics mediate pattern formation in the developing retina. Nature 431, 647–652. Garcia-Bellido, A., Ripoll, P., and Morata, G. (1973). Developmental compartmentalisation of the wing disk of Drosophila. Nat. New Biol. 245, 251–253. Morata, G., and Lawrence, P.A. (1975). Control of compartment development by the engrailed gene in Drosophila. Nature 255, 614–617. Dahmann, C., and Basler, K. (2000). Opposing transcriptional outputs of Hedgehog signaling and engrailed control compartmental cell sorting at the Drosophila A/P boundary. Cell 100, 411–422. Wei, S.Y., Escudero, L.M., Yu, F., Chang, L.H., Chen, L.Y., Ho, Y.H., Lin, C.M., Chou, C.S., Chia, W., Modolell, J. et al. (2005). Echinoid is a component of adherens junctions that cooperates with DE-Cadherin to mediate cell adhesion. Dev. Cell 8, 493–504. Escudero, L.M., Wei, S.Y., Chiu, W.H.,
Wolbachia Genomes: Insights into an Intracellular Lifestyle The genome sequence of the Wolbachia endosymbiont that infects the nematode Brugia malayi has recently been determined together with three partial Wolbachia genomes from different Drosophila species. These data along with the previously published Wolbachia genome from Drosophila melanogaster provide new insights into how this endosymbiont has managed to become so successful. Jeremy C. Brownlie and Scott L. O’Neill* Wolbachia pipientis is a maternally inherited, intracellular bacterium estimated to infect more than 20% of all insect species as well as a range of other invertebrates, including mites, spiders, crustaceans and nematodes. W. pipientis has profound effects on its hosts, ranging from conventional mutualism where it increases host fitness, to reproductive
parasitism. In the latter case, it induces for instance cytoplasmic incompatibility, parthenogenesis, feminization and male-killing [1]. All of the described Wolbachia induced phenotypes benefit the bacterium by enhancing its vertical transmission into host populations. The publication of the sequences of a number of Wolbachia genomes within the last year provides new insights into the biology of this fascinating group of microorganisms. This is especially the case when the
14.
15.
16.
17.
18.
Modolell, J., and Hsu, J.C. (2003). Echinoid synergizes with the Notch signaling pathway in Drosophila mesothorax bristle patterning. Development 130, 6305–6316. Ahmed, A., Chandra, S., Magarinos, M., and Vaessin, H. (2003). Echinoid mutants exhibit neurogenic phenotypes and show synergistic interactions with the Notch signaling pathway. Development 130, 6295–6304. Rawlins, E.L., White, N.M., and Jarman, A.P. (2003). Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups. Development 130, 3715–3724. Bai, J., Chiu, W., Wang, J., Tzeng, T., Perrimon, N., and Hsu, J. (2001). The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway. Development 128, 591–601. Bertet, C., Sulak, L., and Lecuit, T. (2004). Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671. Zallen, J.A., and Wieschaus, E. (2004). Patterned gene expression directs bipolar planar polarity in Drosophila. Dev. Cell 6, 343–355.
Laboratoire de Génétique et de Physiologie du Développement (LGPD), UMR 6545, CNRS-Université de la Méditerrannée, Institut de Biologie du Développement de Marseille (IBDM), Campus de Luminy, case 907, 13288 Marseille cedex 09, France. E-mail: [email protected] DOI: 10.1016/j.cub.2005.06.028
genome sequences of different Wolbachia strains are compared, such as the parasitic Drosophila symbiont wMel [2] and its mutualistic relative wBm [3] which infects the nematode Brugia malayi, a causal agent of filariasis. Repetitive DNA and Genomic Plasticity One of the most striking features of the first Wolbachia genome sequence from the strain wMel was the large amount of repetitive DNA. Like other intracellular bacteria, the size of Wolbachia’s genome is considerably smaller than that of its free living relatives [4]. Despite this obvious streamlining, at least 14% of the wMel genome is composed of numerous repetitive DNA sequences and insertions. These repetitive elements have significantly influenced the genome organisation of wMel by providing sites for recombination
Current Biology Vol 15 No 13 R508
and rearrangements. As a result, there is little colinearity between the genome of the wMel strain and the genome of the related, nematode infecting strain wBm [3]. Unlike Wolbachia that infect insects and display reproductive parasitism traits, filarial nematode Wolbachia are obligate mutualists. They share similarities to other obligate mutualists (e.g. the Buchnera symbionts of aphids) such as concordant phylogenies with their hosts (indicating lack of horizontal transmission) and greatly reduced genome size [3–5]. In contrast, Wolbachia that induce reproductive parasitism traits have considerably larger genomes [2,6], and show phylogenetic evidence of horizontal transfer [7,8]. Compared to wMel, the genome of wBm lacks repetitive DNA and prophage sequences [3]. Considering that repetitive DNA is also absent from the genomes of other mutualistic intracellular symbionts [4], the presence of such a large amount of repetitive sequences in parasitic Wolbachia, like wMel raises the question of its potential adaptive significance [3]. The abundance of repetitive DNA in wMel-like genomes is expected to confer increased plasticity by providing sites for genome shuffling. Such shuffling events are likely to vary gene expression, by interrupting promoter or termination sequences, or by the duplication or deletion of individual genes. Similarly, the potential of phages to transfer genetic material among parasitic Wolbachia strains may help to increase plasticity. This capability may be actively selected as a mechanism that facilitates successful establishment of parasitic Wolbachia within novel host lineages after horizontal transmission. It may also explain the increased phenotypic variability among parasitic Wolbachia strains. Towards a Functional Understanding While the genome sequences of the two strains do not reveal the molecular basis of the various phenotypes that Wolbachia can
induce, they do point towards some potential mechanisms. For example, when considering how Wolbachia might act as a mutualist in the nematode, the genome sequences clearly demonstrate that this cannot be due to the production of amino acids for the host, as is the case in a number of other mutualistic associations [9–11]. Like other Wolbachia strains, wBm appears unable to synthesize a range of amino acids, carbohydrates or essential lipids and presumably acquires these from its host [3]. Interestingly, analysis of the wBm and B. malayi genomes has revealed that both contain incomplete pathways for the synthesis of various coenzymes and cofactors. When both genomes are combined, however, these pathways appear complete [3]. Rather than providing amino acids, wBm appears to be supplying two essential cofactors, riboflavin and heme, to the nematode host [3]. Thus, when Wolbachia are purged from their filarial nematode hosts, the nematodes may be effectively starved of heme and riboflavin, which disrupts proper molting and fecundity. Given these findings, it seems likely that the disruption of this symbiosis will continue to be a focus of research aimed at developing novel filariasis control strategies [12]. While a clear link between Wolbachia derived cofactors and the nematode host can be established, it is less clear which benefit Wolbachia might provide to its insect host? It is known that some Wolbachia that have been largely considered reproductive parasites are also at times capable of positively influencing host fitness [13,14]. It is known that insects suffer from retarded larval development and increased mortality in vitamin deficient environments [15] and that some obligate insect symbionts provision their hosts with vitamins [10]. If Wolbachia are capable of providing additional sources of riboflavin to their developing insect hosts, this could provide a selective advantage in nutritionally deficient or fluctuating environments. It will be of interest
to determine whether Wolbachia can deliver these additional cofactors to insect hosts and whether they may form the basis of the positive effects on fitness in insects. At present, there is great interest in unraveling the molecular basis of the various Wolbachia mediated reproductive parasitism traits that occur in insects. The initial wMel genome sequence identified an exceptionally large number of genes coding for proteins with ankyrin repeat domains. These proteins have many of the characteristics of proteins that might be playing a significant role in the maintenance of symbiosis as well as in the reproductive phenotypes [2,16]. Consistent with this hypothesis is the observation of a very reduced set of ankyrin domain proteins in the wBm genome. Since nematode Wolbachia are not known to reproductively manipulate their hosts, it would be expected that their genomes lack the genes for this capability. Hidden Genomes Another exciting development in Wolbachia research has been the unexpected discovery of a number of partial Wolbachia genomes that have been sequenced as a by-product of other insect genome sequencing projects. These sequences have been lying unnoticed in the trace archives. By mining trace archives, Salzberg and colleagues [17] have reported the recovery of three partial genomes of Wolbachia strains that infect different Drosophila species. This approach could potentially reveal a rich source of new Wolbachia genomic information. However, some caution needs to be taken with these data, as it is possible that the low coverage may result in a number of sequencing errors as well as the possibility of chimeric assemblies from multiple co-infecting symbiont genomes. Despite these limitations, it is very exciting that numerous additional Wolbachia genomes may be potentially sequenced in the course of ongoing and future insect genome projects. These
Dispatch R509
data will further accelerate our understanding of the biology of Wolbachia. References 1. O’Neill, S.L., Hoffmann, A.A., and Werren, J.H. (1997). Influential Passengers. Inherited Microorganisms and Arthropod Reproduction (Oxford: Oxford University Press). 2. Wu, M., Sun, L.V., Vamathevan, J., Riegler, M., Deboy, R., Brownlie, J.C., McGraw, E.A., Martin, W., Esser, C., Ahmadinejad, N., et al. (2004). Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. PLoS Biol. 2, E69. 3. Foster, J., Ganatra, M., Kamal, I., Ware, J., Makarova, K., Ivanova, N., Bhattacharyya, A., Kapatral, V., Kumar, S., Posfai, J., et al. (2005). The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. PLoS Biol. 3, E121. 4. Wernegreen, J.J. (2002). Genome evolution in bacterial endosymbionts of insects. Nat. Rev. Genet. 3, 850–861. 5. Andersson, J.O., and Andersson, S.G. (1999). Genome degradation is an ongoing process in Rickettsia. Mol. Biol. Evol. 16, 1178–1191. 6. Sun, L.V., Foster, J.M., Tzertzinis, G., Ono, M., Bandi, C., Slatko, B.E., and O’Neill, S.L. (2001). Determination of
Wolbachia genome size by pulsed-field gel electrophoresis. J. Bacteriol. 183, 2219–2225. 7. Werren, J.H., Zhang, W., and Guo, L.R. (1995). Evolution and phylogeny of Wolbachia: reproductive parasites of arthropods. Proc. Biol. Sci. 261, 55–63. 8. O’Neill, S.L., Giordano, R., Colbert, A.M., Karr, T.L., and Robertson, H.M. (1992). 16S rRNA phylogenetic analysis of the bacterial endosymbionts associated with cytoplasmic incompatibility in insects. Proc. Natl. Acad. Sci. USA 89, 2699–2702. 9. Baumann, P., Baumann, L., Lai, C.Y., Rouhbakhsh, D., Moran, N.A., and Clark, M.A. (1995). Genetics, physiology, and evolutionary relationships of the genus Buchnera: intracellular symbionts of aphids. Annu. Rev. Microbiol. 49, 55–94. 10. Akman, L., Yamashita, A., Watanabe, H., Oshima, K., Shiba, T., Hattori, M., and Aksoy, S. (2002). Genome sequence of the endocellular obligate symbiont of tsetse flies, Wigglesworthia glossinidia. Nat. Genet. 32, 402–407. 11. Gil, R., Silva, F.J., Zientz, E., Delmotte, F., Gonzalez-Candelas, F., Latorre, A., Rausell, C., Kamerbeek, J., Gadau, J., Holldobler, B., et al. (2003). The genome sequence of Blochmannia floridanus: comparative analysis of reduced genomes. Proc. Natl. Acad. Sci. USA 100, 9388–9393. 12. Taylor, M.J., and Hoerauf, A. (2001). A new approach to the treatment of
Fungal Genomics: Forensic Evidence of Sexual Activity The genome sequence of the ‘asexual’ human pathogenic fungus Aspergillus fumigatus suggests it has the capability to undergo mating and meiosis. That this organism engages in clandestine sexual activity is also suggested by observations of two equally distributed complementary mating types in nature, the expression of mating type genes and evidence of recent genome recombination events. Neil A.R. Gow The completion of the genome sequences of three Aspergillus species provides a resource to explore new avenues of fungal biology and evolution. Three genome centres — the Institute for Genome Research (TIGR), The Wellcome Sanger Genome Centre and The National Institute of Technology and Evaluation (NITE) in Japan — have collaborated with three rather separate scientific communities to sequence and annotate the genomes of three filamentous fungi with contrasting claims to fame. Aspergillus nidulans has a long tradition as a model eukaryote, and was the organism in which many basic findings
about growth and nuclear division were discovered; A. oryzae is an important fungus in industrial fermentation of sake, soy sauce and miso; and A. fumigatus is infamous as a pernicious pathogen of the immunocompromised. On the heels of the publication of the Aspergillus genome sequences comes an important new biological advance, reported in this issue of Current Biology: Dyer and colleagues [1] have used the sequence of A. fumigatus to obtain evidence that this fungus, traditionally classified amongst the asexual or so-called ‘imperfect’ fungi, may have been holding back the truth about its sexuality. Rather than being asexual, it seems to have the
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filariasis. Curr. Opin. Infect. Dis. 14, 727–731. Fry, A.J., Palmer, M.R., and Rand, D.M. (2004). Variable fitness effects of Wolbachia infection in Drosophila melanogaster. Heredity 93, 379–389. Dobson, S.L., Rattanadechakul, W., and Marsland, E.J. (2004). Fitness advantage and cytoplasmic incompatibility in Wolbachia single- and superinfected Aedes albopictus. Heredity 93, 135–142. Bruins, B.G., Scharloo, W., and Thorig, G.E. (1997). Light-induced vitamin deficiency in Drosophila melanogaster. Arch. Insect Biochem. Physiol. 36, 51–67. Iturbe-Ormaetxe, I., Burke, G.R., Riegler, M., and O’Neill, S.L. (2005). Distribution, gene expression and motif variability of ankyrin domain genes in Wolbachia pipientis. J. Bacteriol., in press. DOI: 10.1128/jb.187.15.000-000.2 Salzberg, S.L., Hotopp, J.C., Delcher, A.L., Pop, M., Smith, D.R., Eisen, M.B., and Nelson, W.C. (2005). Serendipitous discovery of Wolbachia genomes in multiple Drosophila species. Genome Biol. 6, R23.
School of Integrative Biology, University of Queensland, Brisbane, Qld 4072, Australia. *E-mail: [email protected] DOI: 10.1016/j.cub.2005.06.029
genetic machinery to mate, develop a sexual fruiting body and undergo a full meiotic cycle. The significance of this relates to the importance of A. fumigatus as a pathogen and difficulties in its genetic analysis. It is appropriate for this fungus to be named after its ability to produce a smoke trail, or fumus, of conidial spores, as these are the agents of infection and route of infection into the lung. The fungus is a common mould of compost and plant surfaces and it is estimated that a cubic metre of air contains 1-10 conidia, which most people will inhale with no ill effect [2]. But in the immunocompromised patient, who lacks the normally efficient surveillance of pulmonary macrophages and circulating monocytes and neutrophils, the spores germinate. The ensuing invasive filamentous growth in the lung and other body sites results in a disease which 80–90% of patients will not survive, even with best available antifungal treatments [3,4]. The severity of systemic aspergillosis has fuelled efforts to understand the nature of the virulence traits of this pathogen