Comparative Genomics of Trypanosomatid Parasitic Protozoa El-Sayed, Najib M; Myler, Peter J; Blandin, Gae̊lle ...
Science (American Association for the Advancement of Science),
07/2005, Letnik:
309, Številka:
5733
Journal Article
Recenzirano
A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed ...a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that--along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions--have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.
Candida dubliniensis is the closest known relative of Candida albicans, the most pathogenic yeast species in humans. However, despite both species sharing many phenotypic characteristics, including ...the ability to form true hyphae, C. dubliniensis is a significantly less virulent and less versatile pathogen. Therefore, to identify C. albicans-specific genes that may be responsible for an increased capacity to cause disease, we have sequenced the C. dubliniensis genome and compared it with the known C. albicans genome sequence. Although the two genome sequences are highly similar and synteny is conserved throughout, 168 species-specific genes are identified, including some encoding known hyphal-specific virulence factors, such as the aspartyl proteinases Sap4 and Sap5 and the proposed invasin Als3. Among the 115 pseudogenes confirmed in C. dubliniensis are orthologs of several filamentous growth regulator (FGR) genes that also have suspected roles in pathogenesis. However, the principal differences in genomic repertoire concern expansion of the TLO gene family of putative transcription factors and the IFA family of putative transmembrane proteins in C. albicans, which represent novel candidate virulence-associated factors. The results suggest that the recent evolutionary histories of C. albicans and C. dubliniensis are quite different. While gene families instrumental in pathogenesis have been elaborated in C. albicans, C. dubliniensis has lost genomic capacity and key pathogenic functions. This could explain why C. albicans is a more potent pathogen in humans than C. dubliniensis.
Theileria annulata and T. parva are closely related protozoan parasites that cause lymphoproliferative diseases of cattle. We sequenced the genome of T. annulata and compared it with that of T. parva ...to understand the mechanisms underlying transformation and tropism. Despite high conservation of gene sequences and synteny, the analysis reveals unequally expanded gene families and species-specific genes. We also identify divergent families of putative secreted polypeptides that may reduce immune recognition, candidate regulators of host-cell transformation, and a Theileria-specific protein domain frequently associated in Theileria (FAINT) present in a large number of secreted proteins.
In budding yeast, the silent information regulator Sir2p is a nuclear NAD‐dependent deacetylase that is essential for both telomeric and rDNA silencing. All eukaryotic species examined to date have ...multiple homologues of Sir two (HSTs), which share a highly conserved globular core domain. Here we report that yeast Hst2p and a mammalian Hst2p homologue, hSirT2p, are cytoplasmic in yeast and human cells, in contrast to yHst1p and ySir2p which are exclusively nuclear. Although yHst2p cannot restore silencing in a sir2 deletion, overexpression of yHst2p influences nuclear silencing events in a SIR2 strain, derepressing subtelomeric silencing while increasing repression in the rDNA. In contrast, a form of ySir2p carrying a point mutation in the conserved core domain disrupts both telomeric position effect (TPE) and rDNA repression at low expression levels. This argues that non‐nuclear yHst2p can compete for a substrate or ligand specifically required for telomeric, and not rDNA repression.
In the fungus Pneumocystis carinii, at least three gene families (PRT1, MSR, and MSG) have the potential to generate high-frequency antigenic variation, which is likely to be a strategy by which this ...parasitic fungus is able to prolong its survival in the rat lung. Members of these gene families are clustered at chromosome termini, a location that fosters recombination, which has been implicated in selective expression of MSG genes. To gain insight into the architecture, evolution, and regulation of these gene clusters, six telomeric segments of the genome were sequenced. Each of the segments began with one or more unique genes, after which were members of different gene families, arranged in a head-to-tail array. The three-gene repeat PRT1-MSR-MSG was common, suggesting that duplications of these repeats have contributed to expansion of all three families. However, members of a gene family in an array were no more similar to one another than to members in other arrays, indicating rapid divergence after duplication. The intergenic spacers were more conserved than the genes and contained sequence motifs also present in subtelomeres, which in other species have been implicated in gene expression and recombination. Long mononucleotide tracts were present in some MSR genes. These unstable sequences can be expected to suffer frequent frameshift mutations, providing P. carinii with another mechanism to generate antigen variation.
In wild-type budding yeast strains, the proteins encoded by SIR3, SIR4 and RAP1 co-localize with telomeric DNA in a limited number of foci in interphase nuclei. Immunostaining of Sir2p shows that in ...addition to a punctate staining that coincides with Rap1 foci, Sir2p localizes to a subdomain of the nucleolus. The presence of Sir2p at both the spacer of the rDNA repeat and at telomeres is confirmed by formaldehyde cross-linking and immunoprecipitation with anti-Sir2p antibodies. In strains lacking Sir4p, Sir3p becomes concentrated in the nucleolus, by a pathway requiring SM2 and UTH4, a gene that regulates life span in yeast. The unexpected nucleolar localization of Sir2p and Sir3p correlates with observed effects of sir mutations on rDNA stability and yeast longevity, defining a new site of action for silent information regulatory factors.
A second-hand ticket to the end-game Renauld, Hubert
Trends in biochemical sciences (Amsterdam. Regular ed.),
10/1998, Letnik:
23, Številka:
10
Journal Article
Recenzirano
Telomeres and Telomerase (Ciba Foundation Symposium 211)
edited by
Derek J. Chadwick and
Gail Cardew, John Wiley, 1997. £57.50 (ix+238 pages) ISBN 0 471 97278 9
Act I, Scene 1. London, February. An ...empty (a class-?) room with bright lights, a coffee machine, overhead and slide projectors, a screen, a board, twenty-nine chairs. Twenty-nine people, dressed as scientists, enter the room. Some (about fourteen) carry presentation material; the others do not. They know each other; conversations are vivid.
The
Trypanosoma brucei reference strain TREU927/4 exhibits some resistance to lysis by normal human serum (NHS), but this resistance is never complete even after selection. The genome of this strain ...contains a minimum of eight sequences related to the
T. brucei rhodesiense-specific serum resistance-associated gene (
SRA), which encodes a truncated variant surface glycoprotein (VSG) conferring full resistance to lysis by NHS. We selected two sequences showing the highest similarity to
SRA and also preceded by a region (“cotransposed region”) present immediately upstream from
SRA in the
VSG expression site termed R-ES, where
SRA is expressed in
T. brucei rhodesiense. Whereas one of these sequences appears to be a pseudogene, the other, which is contained within a cluster of
VSG basic copies (BCs), encodes a VSG truncated in the C-terminal domain. In the latter gene, an inserted region encoding surface-exposed loops similar to those of the
BoTat 1.20 VSG interrupts the full SRA sequence. Therefore, this gene was termed
SRA-BC, for the putative
VSG basic copy from which
SRA was derived. Neither this gene nor other
SRA-like sequences appeared to be responsible for the relative resistance of TREU927/4 to NHS, since (i) transfection of
SRA-BC in
T. brucei brucei did not confer increased resistance; (ii)
SRA transcripts could not be detected in this strain, even when focusing the search on the limited
SRA sequence necessary to confer resistance and when using strain-specific
SRA probes on RNA from cells selected in the presence of NHS.
During meiosis, the pairing of chromosomes is crucial for a successful partitioning of the genetic material and its transmission into the developing gamete. The classical view of meiotic pairing ...involves recombination between homologues as an integral part of the pairing mechanism. But, in cases where no recombination occurs, how do chromosome partners find one another? And how do they pair up and then segregate appropriately? Recently, a combination of molecular genetics and fluorescence in situ hybridization appears to have provided an answer to these questions by demonstrating a crucial role for heterochromatin in chromosome pairing.
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