The Constitution of a New Model Army

Genome basis of working together for a common good

CLUSTALX alignment of sequences encompassing the seven transmembrane domains of all Dictyostelium GPCRs. These and selected GPCRs from other organisms were then used to create an unrooted dendrogram.

Democratic elections are the times when the actions of the majority form the basis for the future of the whole; individual citizens gather together to take part in deciding how they all will live. Today, Thursday 5 May 2005, the biological constitution of a remarkable organism that votes with its feet is published in Nature by a team of scientists from the UK, USA, Germany, Japan and France.

Dictyostelium discoideum, known as Dicty to researchers, spends most of its time living alone in the soil as a single-celled amoeba. However, in a food shortage the individual cells ‘talk’ to each other, aggregate and then develop into a multicellular organism that produces spores, the only survivors of the time of hunger. This unique and seemingly simple development has helped biologists understand how, for example, cells in the human immune system communicate and how that process can go wrong in disease. It is even being used to try to understand the treatment of bipolar disorder.

“Were it not for its tiny size and unwieldly name, Dictyostelium would be familiar to us all as one of the more bizarre forms of life on Earth. It represents a branch of life that we now know parted company from animals shortly after plants and animals went their separate ways. Its DNA sequence, now an open book for researchers worldwide, shares genes with plants, animals and fungi, and promises to shed light on many fundamental aspects of biology.”

Paul Dear A lead scientist from the MRC Laboratory of Molecular Biology, Cambridge, UK

As a single cell, Dicty is ideal for mutation – the first choice from the geneticists’ toolbox – and many of its biochemical processes have been modified, revealing the underlying chemistry of life. But its development from single cell to true multicellular organism makes it more valuable as a model, allowing biologists to define the ways in which cells in complex organisms such as ourselves talk to each other. Cell communication is an absolute requirement for multicellular life.

The genome sequence consists of 34 million base-pairs – letters of genetic code – that contain the instructions for 12,500 proteins – about half as many as the human genome and more than twice as many as simple yeasts. Among these are genes involved in complex processes characteristic of multicellular life – communication, adhesion, movement – that cannot be modelled in simpler species.

However, Dicty is not a pared down human or a complex fungus. It shows a unique combination of conserved and lost functions that span the kingdoms of bacteria, plants and animals in a compact genome.

“The genome of Dictyostelium discoideum is one of the most distinctive analysed so far, reflecting the intriguing biology of this organism. The chromosomes have an unusual structure, the genome is nearly 80 per cent A and T residues, whereas our genome is 40 per cent As and Ts, and it makes special use of ribosomal genes that is unique to known biology.”

Marie-Adele Rajandream Leader of the sequencing component at the Wellcome Trust Sanger Institute

More than one-tenth of the genome is composed of simple repeated sequences, 2-6 bases repeated over and over again. Expansion of the number of copies of simple repetitive sequences are characteristic of some human diseases, such as myotonic dystrophy and Huntington’s disease, and understanding why and how these repeats are tolerated in Dicty will help to understand human disease development.

A search for versions of genes in Dicty that resembled genes involved in human disease found that between 10 and 20 per cent are conserved. These include nine cancer genes as well as genes similar to those implicated in human Parkinson’s, Tay-Sachs and cystic fibrosis.

For several decades, Dictyostelium has been studied in laboratories around the world as a perfect test-bed in which to study processes such as how cells move and how individual cells specialize and coordinate to form complex organisms. The solitary amoeba shares many features with our own cells, particularly those which patrol our bodies and engulf harmful bacteria.

Just as important have been the insights into developmental biology – how all complex life forms develop from a single cell to a multicellular organism in which cells share duties and differentiate into specialized functions. When Dicty is starved, each cell sends a pulse of a chemical called cyclic AMP and, gradually, these pulses become synchronized and the cells ‘swim’ in waves towards the highest concentration of cAMP. The result is an aggregate of cells, which form a mobile ‘slug’ and then a delicate spore- bearing fruiting body. Many of the molecules identified in Dicty that underlie the processes of differentiation in other species.

Model organisms play an essential role in biology and medicine: our understanding of human diseases has, in many cases, been derived from studies in other organisms. From yeasts came genes involved in cell division and cancer in humans; from worms came genes involved in development, cell death and cancer; and from Dicty have come new details of cell communication and cell movement.

The genome sequence has been used to identify ‘novel’ proteins that will fill gaps in pathways in Dicty biology. The sequence will enrich our understanding of this remarkable organism and our understanding of our own biology.

More information

Participating Centres

• Center for Biochemistry and Center for Molecular Medicine Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Cologne, Germany
• MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK
• Genome Analysis, Institute for Molecular Biotechnology, Beutenbergstr. 11, D-07745 Jena, Germany
• The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
• Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
• Section of Cell and Developmental Biology, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA
• Dept. of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77030, USA
• Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
• dictyBase, Center for Genetic Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL 60611, USA
• Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
• Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
• Adolf-Butenandt-Institute/Cell Biology, Ludwig-Maximilians-University, 80336 Munich, Germany
• Biochemistry Department, University of Cambridge, Cambridge CB2 1QW, UK
• Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810 Japan
• Unité de Genomique des Microorganismes Pathogenes, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France
• Department of Biology, University of York, York YO10 5YW, UK
• MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK
• Centre for Genetic Resource Information, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
• Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato, Tokyo 108-8639, Japan
• Institut für Pharmazeutische Biologie, Universität Frankfurt (Biozentrum), Frankfurt am Main, 60439, Germany
• Department of Molecular Biology, Princeton University, Princeton, NJ08544-1003, USA
• School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK