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dictyNews
Electronic Edition
Volume 36, number 7
March 4, 2011

Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to [log in to unmask]
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.

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=========
Abstracts
=========

Comparative genomics of the social amoebae Dictyostelium discoideum 
and Dictyostelium purpureum 

Richard Sucgang1*, Alan Kuo2*, Xiangjun Tian3*, William Salerno1*, Anup Parikh4, 
Christa L. Feasley5, Eileen Dalin2, Hank Tu2, Eryong Huang4, Kerrie Barry2, 
Erika Lindquist2, Harris Shapiro2, David Bruce2, Jeremy Schmutz2, Asaf Salamov2, 
Petra Fey6, Pascale Gaudet6, Christophe Anjard7, M. Madan Babu8, Siddhartha Basu6, 
Yulia Bushmanova6, Hanke van der Wel5, Mariko Katoh-Kurasawa4, Christopher Dinh1, 
Pedro M. Coutinho9, Tamao Saito10, Marek Elias11, Pauline Schaap12, Robert R. Kay8, 
Bernard Henrissat9, Ludwig Eichinger13, Francisco Rivero14, Nicholas H. Putnam3, 
Christopher M. West5, William F. Loomis7, Rex L. Chisholm6, Gad Shaulsky3,4, 
Joan E. Strassmann3, David C. Queller3, Adam Kuspa1,3,4,†, and Igor V. Grigoriev2

1Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor 
College of Medicine, Houston, TX 77030 
2U.S. Department of Energy Joint Genome Institute, Walnut Creek CA 
3Department of Ecology and Evolutionary Biology, Rice University, Houston, TX 77005; 
4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
TX 77030 
5Department of Biochemistry & Molecular Biology, Oklahoma Center for Medical 
Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
6dictyBase, Center for Genetic Medicine, Northwestern University, 750 N Lake Shore 
Drive, Chicago, Illinois 60611
7Section of Cell and Developmental Biology, Division of Biology, University of California, 
San Diego, La Jolla, California 92093
8Laboratory of Molecular Biology, MRC Centre, Cambridge CB2 2QH, UK
9Architecture et Fonction des Macromolécules Biologiques, UMR6098, CNRS, 
Universities of Aix-Marseille I & II, 13288 Marseille, France
10Department of Materials and Life Sciences, Sophia University 7-1 Kioi-Cho, 
Chiyoda-Ku, Tokyo, Japan 102-8554
11Departments of Botany and Parasitology, Faculty of Science, Charles University 
in Prague, Prague, Czech Republic
12College of Life Sciences, University of Dundee, DD15EH Dundee, UK
13Center for Molecular Medicine Cologne, University of Cologne, Joseph-Stelzmann-Str. 
52, 50931 Cologne, Germany
14Centre for Biomedical Research, The Hull York Medical School and Department of 
Biological Sciences, University of Hull, Hull HU6 7RX, UK.


Genome Biology, in press

Background:
The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve 
multicellularity by aggregation and undergo morphogenesis into fruiting bodies with 
terminally differentiated spores and stalk cells. There are four groups of dictyostelids, 
with the most derived being a group that contains the model species Dictyostelium 
discoideum. 
Results: 
We have produced a draft genome sequence of another group Dictyostelid, Dictyostelium 
purpureum, and compare it to the D. discoideum genome. The assembly (8.41x coverage) 
comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. 
Sequence comparisons suggest that these two Dictyostelids shared a common ancestor 
approximately 400 million years ago. In spite of this divergence, most orthologs reside in 
small clusters of conserved synteny. Comparative analyses revealed a core set of 
orthologous genes that illuminate Dictyostelid physiology, as well as differences in gene 
family content. Interesting patterns of gene conservation and divergence are also evident 
suggesting function differences; some protein families, such as the histidine kinases, 
have undergone little functional change, whereas others, such as the polyketide synthases, 
have undergone extensive diversification. The abundant amino acid homopolymers 
encoded in both genomes are generally not found in homologous positions within proteins, 
so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the 
social stage evolved more rapidly than others, consistent with either relaxed selection 
or accelerated evolution due to social conflict.
Conclusion:
The findings from this new genome sequence and comparative analysis shed light on 
the biology and evolution of the Dictyostelia.


Submitted by Adam Kuspa [[log in to unmask]]
--------------------------------------------------------------------------------


Deficiency of huntingtin has pleiotropic effects in the social amoeba 
Dictyostelium discoideum

Michael A. Myre1, Amanda L. Lumsden1, Morgan N. Thompson1, 
Wilma Wasco2, Marcy E. MacDonald1 and James F. Gusella1

1Molecular Neurogenetics Unit, Center for Human Genetic Research, 
Massachusetts General Hospital, Boston MA 02114. 

2Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative 
Disease, Massachusetts General Hospital, Charlestown MA 02129. 

PLoS Genetics, in press

Huntingtin is a large HEAT repeat protein first identified in humans, where a polyglutamine 
tract expansion near the amino terminus causes a gain-of-function mechanism that leads 
to selective neuronal loss in Huntington’s disease (HD). Genetic evidence in humans and 
knock-in mouse models suggests that this gain-of-function involves an increase or 
deregulation of some aspect of huntingtin’s normal function(s), which remains poorly 
understood. As huntingtin shows evolutionary conservation, a powerful approach to 
discovering its normal biochemical role(s) is to study the effects caused by its deficiency 
in a model organism with a short life-cycle that comprises both cellular and multicellular 
developmental stages. To facilitate studies aimed at detailed knowledge of huntingtin’s 
normal function(s), we generated a null mutant of hd, the HD ortholog in Dictyostelium 
discoideum. Dictyostelium cells lacking endogenous huntingtin were viable but during 
development did not exhibit the typical polarized morphology of Dictyostelium cells, 
streamed poorly to form aggregates by accretion rather than chemotaxis, showed 
disorganized F-actin staining, exhibited extreme sensitivity to hypoosmotic stress, 
and failed to form EDTA-resistant cell-cell contacts. Surprisingly, chemotactic 
streaming could be rescued in the presence of the bivalent cations Ca2+ or Mg2+ 
but not pulses of cAMP. Although hd- cells completed development, it was delayed 
and proceeded asynchronously, producing small fruiting bodies with round, defective 
spores that germinated spontaneously within a glassy sorus. When developed as 
chimeras with wild-type cells, hd- cells failed to populate the pre-spore region of the 
slug. In Dictyostelium, huntingtin deficiency is compatible with survival of the organism 
but renders cells sensitive to low osmolarity which produces pleiotropic cell autonomous 
defects that affect cAMP signaling, and as a consequence development. Thus, 
Dictyostelium provides a novel haploid organism model for genetic, cell biological 
and biochemical studies to delineate the functions of the HD protein.



Submitted by Michael Myre [[log in to unmask]]
--------------------------------------------------------------------------------

A Dictyostelium SH2 adaptor protein required for correct DIF-1 signaling and 
pattern formation


Christopher Sugden1, Susan Ross1, Sarah J. Annesley4, Christian Cole1, 
Gareth Bloomfield3, Alasdair Ivens2 Jason Skelton2, Paul R. Fisher4, 
Geoffrey Barton1 and Jeffrey G. Williams1*

1School of Life Sciences, University of Dundee, Dow St., Dundee, DD1 5EH UK
2Wellcome Trust Sanger Institute, Hinxton, CB10 1SA UK
3MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH UK
4Department of Microbiology, La Trobe University, Bundoora, Victoria 3086, Australia
* Corresponding Author
[log in to unmask]
tel 44 1382 385220, 
fax 44-1382 34421


Dev. Biol., in press

Dictyostelium is the only non-metazoan with functionally analysed SH2 domains
and studying them can give insights into their evolution and wider potential. LrrB 
has a novel domain configuration with leucine-rich repeat, 14-3-3 and SH2 
protein-protein interaction modules. It is required for the correct expression of 
several specific genes in early development and here we characterize its role in 
later, multicellular development. During development in the light, slug formation 
in LrrB null (lrrB-) mutants is delayed relative to the parental strain, and the slugs 
are highly defective in phototaxis and thermotaxis. In the dark the mutant arrests 
development as an elongated mound, in a hitherto unreported process we term 
dark stalling. The developmental and phototaxis defects are cell autonomous and 
marker analysis shows that the pstO prestalk sub-region of the slug is aberrant in 
the lrrB- mutant. Expression profiling, by parallel micro-array and deep RNA 
sequence analyses, reveals many other alterations in prestalk-specific gene 
expression in lrrB- slugs, including reduced expression of the ecmB gene and 
elevated expression of ampA. During culmination ampA is ectopically expressed 
in the stalk, there is no expression of ampA and ecmB in the lower cup and the 
mutant fruiting bodies lack a basal disc. The basal disc cup derives from the pstB 
cells and this population is greatly reduced in the lrrB- mutant. This anatomical 
feature is a hallmark of mutants aberrant in signalling by DIF-1, the polyketide 
that induces prestalk and stalk cell differentiation. In a DIF-1 induction assay 
the lrrB- mutant is profoundly defective in ecmB activation but only marginally 
defective in ecmA induction. Thus the mutation partially uncouples these two 
inductive events. In early development LrrB interacts physically and functionally 
with CldA, another SH2 domain containing protein. However, the CldA null 
mutant does not phenocopy the lrrB- in its aberrant multicellular development 
or phototaxis defect, implying that the early and late functions of LrrB are 
effected in different ways. These observations, coupled with its domain 
structure, suggest that LrrB is an SH2 adaptor protein active in diverse 
developmental signaling pathways. 


Submitted by: Jeff Williams [[log in to unmask]]
==============================================================
[End dictyNews, volume 36, number 7]

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