Award details

Comparative genome analysis in social amoebas

Reference	BB/E016308/1
Principal Investigator / Supervisor	Professor Pauline Schaap
Co-Investigators / Co-Supervisors	Dr Nicholas Helps
Institution	University of Dundee
Department	College of Life Sciences
Funding type	Research
Value (£)	397,334
Status	Completed
Type	Research Grant
Start date	07/05/2007
End date	06/01/2011
Duration	44 months

Abstract

Social amoebae display conditional multicellularity with a broad range of forms. One species, D.discoideum, is widely used to investigate a range of cell- and developmental questions. Its genome is completely sequenced by an international consortium. We use the social amoebas to study the origin of phenotypic diversity across species and started with the construction of their molecular phylogeny. This tree shows subdivision into four major groups: D.discoideum is placed in the most derived group 4, while the root of the tree lies between groups 1 and 2. Cyclic AMP is a major regulator of D.discoideum development, and we used a PCR-based approach to identify cAMP signalling genes in species that span the phylogeny. This work showed that the use of extracellular cAMP as chemoattractant in group 4 species is derived from a role in coordinating fruiting body formation in basal species. Proximal-to-distal addition of novel promoters appeared to provide existing genes with novel roles in Dictyostelid evolution. The PCR approach has many obvious limitations, which would be overcome if representative genome sequences were available. The Dictyostelium Sequencing Consortium aim to sequence at least one genome from each of the 4 groups. The US team started draft sequencing of another group 4 species. The German team obtained funding for draft sequencing of the D.fasciculatum (group 1) and P.pallidum (group 2). The latter species is important because of its basal position and genetic tractability. The draft sequences provide a preliminary gene inventory. However, our research requires complete information about taxon specific gene gains- and losses, as well as complete promoter sequences. I therefore request funding for sequencing the P.pallidum genome to completion. The information will be used to study the evolution of developmental signalling and to test the hypothesis that elaboration of promoters is a major mechanism for generation of phenotypic novelty.

Summary

Biologists try to understand how complex multicellular organisms have evolved from simple single-celled ancestors. We know in theory how this happened: spontaneous mutations in the genes of earlier organisms caused small changes in the developmental program of their off-spring. This sometimes resulted in an improved adult that more successfully reproduced, and therefore gradually replaced the earlier form. However, to really understand this process and prove that it actually occurred, we have to trace back which genes were mutated and how this mutation changed gene function and consequently the developmental program. Because it is difficult to obtain such detailed information for complex organisms like ourselves, we investigate this problem in the social amoebas. Social amoebas feed as single cells on bacteria in forest soil. However, when starving, they come together and form a fruiting structure, in which a proportion of cells is preserved as spores. The other cells are sacrificed to form a stalk that aids in spore dispersal. This life style depends on mutual collaboration and specialization of cells. In the course of evolution the social amoebae have progressed from basal species that form structures with 10-100 cells and only two cell-types, to advanced species that form structures with over 100.000 cells and up to five cell types. One advanced species, Dictyostelium discoideum, is used widely as a model system to understand how cells move, feed and propagate and how they communicate with each other to achieve multicellularity. The D.discoideum genome has been completely sequenced, which means that we have a complete inventory of all the genes that control these processes. D.discoideum uses cyclic AMP (cAMP) as the major signal molecule for cell-cell communication. It acts as a chemoattractant to bring starving cells together, and then continues to guide cells to build a fruiting body. cAMP also induces the differentiation of the spores and regulates the processof spore germination. In previous BBSRC-funded research we constructed a family tree of the social amoebas, which shows that they are subdivided into four major groups. D.discoideum belongs to the most evolved group 4. From species in all four groups, we obtained fragments of the genes that are necessary for cAMP signalling by gene amplification. This suggests that many roles of cAMP are conserved. However, between groups, we observed changes in the stage of development at which these genes are active. One such as change gave rise to the use of cAMP as chemoattractant in the group 4 species. Gene amplification can only be used for very deeply conserved genes and only provides information on small regions of DNA. For many reasons it would be much better to compare species evolution at the level of the entire genome. With this project we therefore propose to sequence the genome of Polysphondylium pallidum to completion. This work will be performed in collaboration with a German team, who already obtained funding for draft sequencing of the P.pallidum genome. P.pallidum is particularly suitable for evolutionary studies because it occupies a basal position in the family tree and it is one of the few Dictyostelids that is readily accessible for gene manipulation. The complete P.pallidum genome sequence will give us the complete inventory and sequences of all cAMP signalling genes, and very importantly, will also tell us which genes are missing. By identifying gene losses and gains, and by comparing genes that are conserved between D.discoideum and P.pallidum, we can detect the genetic changes that occurred in the course of evolution. The completed P.pallidum genome will also be of great benefit for the Dictyostelium and broader research community. For instance, it can be used to identify conserved regions in proteins with important roles, that are thus far not well characterized.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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