DECEMBER 7, 1999 meeting
Agenda (Changed slightly at the meeting): Presentation by Fiona and discussion about the Trichomonas vaginalis sialic acid lyase gene recently identified that shares high similarity with the corresponding gene in Pasteurellaceae bacteria. Discussion of other items that groups members had indicated they wish to bring up.
Summary:
· The next meeting has been set for Tuesday morning, January 11th at 9 am in NCE 403. All subsequent meetings are being scheduled for the first Tuesday of the month (with the exception of February, in order to ensure that all dates are a minimum of a month apart). You should view the complete meetings schedule for this Winter and Summer and mark these dates in your calendar.
- Trichomonas vaginalis sialic acid lyase gene: It appears to have evolved from a gene horizontally transferred from a bacterium of the Pasteurellaceae (or related family). A large phylogenetic tree based on all related genes (including those from unfinished microbial genomes) will be constructed by Audrey to better evaluate the evolutionary history of this gene and related genes. There was some discussion regarding functional significance of this gene, particularly as it pertains to pathogenicity. It was agreed that, while we don’t know the true benefit this gene would confer on this organism, there are a number of possibilities.
- The issues of authorship of papers resulting from pathogenomics work, and limits for the inclusion of new members in the group was initiated by Francis. It was agreed that persons directly involved in work leading to publication would be authors on papers, and that inclusion in the group did not necessarily guarantee inclusion on a paper. However, at one point there will likely be a paper written summarizing this approach and results and such a paper could include a large number of group members, reflecting the interdisciplinary nature of the group. Regarding the addition of new members, it was decided that unless they had significant expertise to contribute to the group, new members would not be encouraged, to prevent the size of the group from expanding to an unwieldy number.
- Steve mentioned items he has now dealt with on the “Database Wish List”. It was decided to include a list of what is completed on the Pathogenomics Reference web site. Steve also mentioned at the end of the meeting that he will have a co-op student, Ivan Wan, working for him starting in January who will be working on some of the Pathogenomics Database modifications.
- Bob Brunham brought up two issues he wished to discuss with the group: Studies of gene fusions as an indicator of protein-protein interaction (see related paper), and a proposal that the BC Genome Sequence Centre consider sequencing the genome of Yersinia enterocolitica and possibly Yersinia pseudotuberculosis.
- Agenda for the next meeting will be to go over more trees of notable genes from the database, and to discuss the “Database Wish List” (proposing further changes and evaluating priorities – please note the certain items on the list are difficult and so priorities will be developed in that context).
Further information: The Trichomonas vaginalis sialic acid lyase gene, items Bob Brunham raised, and Database modifications Steve Jones has completed:
A brief summary of the information Fiona presented on the T. vaginalis sialic acid lyase gene is available but is not shown here for brevity. Discussion at the meeting included the following points:
- Sialic acid lyase is a member of a superfamily of proteins that share significant similarity with each other. It is difficult to evaluate which proteins definitively have this activity, without appropriate enzymatic study. Many of the relevant sialic acid lyases have been functionally studied through enzyme assays (Trichomonas vaginalis. Haemophilus influenzae, Pasteurella haemolytica, Clostridium perfringens, Escherichia coli) however Yossi mentioned that the methodology for these assays needs to be examined in more detail to determine if they were properly examining substrate specificity of the enzymes.
- Bob Brunham initiated discussions of the possible role in pathogenicity of this gene. It is unclear exactly what role such a gene would play in pathogenicity, since it is involved primarily in catabolizing free sialic acid rather than sialic acid bound to macromolecules, and the enzyme appears to be excreted. However, such activity may increase this protist’s general ability to manage the sialic acid that’s been demonstrated to coat its surface, and detoxify the excess sialic acid present in the microbes environment when infecting host tissues. A source of nutrients is also a possibility, as the products of the sialic acid catabolism include pyruvate, which could likely be taken up by this protist.
- The T. vaginalis gene appears to have a slightly atypical G+C content (42% verses 48%), while all other sialic acid lyases examined have a G+C within approximately 1% of the average for all genes in the given genome. However, as only 47 genes are listed for T. vaginalis in the Codon Usage Database used, Patrick was concerned that there are not enough genes in the database to determine an accurate average G+C for genes in this genome.
- Further discussion regarding the evolution of these sialic acid lyases should proceed after a large phylogenetic tree is constructed containing all relevant genes from all databases including the unfinished genomes (to be completed by Audrey).
Items raised by Bob Brunham:
- Bob proposed that the BC Genome Sequence Centre consider sequencing the genome of Yersinia enterocolitica. Reasons for this were multifold and included the high number of cases of Y. enterocolitica in British Columbia (which may increase the chances of obtaining local BC funding), and the fact that the genome of the related pathogen Yersinia pestis is currently being sequenced and may be used for comparison. Also, Yersinia pseudotuberculosis may be sequenced. Francis mentioned that it would be useful for Bob to gather information such as genome size and genome G+C content to evaluate the ease in which the genome may be sequenced. Also items such as the level of fold coverage of the genome would need to be evaluated (i.e. is a rough 2x coverage of the genome adequate, or is a more complete sequencing of the genome necessary?).
- Bob referred to a paper by Enright et al., published last month in Nature, that’s entitled “Protein interaction maps for complete genomes based on gene fusion events”. This paper essentially uses gene fusions events as an indicator of protein-protein interactions. He would be interested in such an analysis being pursued for all the pathogen genomes to provide further insight into protein interactions in these organisms.