The Constitution Of A New Model Army: Genome Basis Of Working Together For A Common Good

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.

Paul Dear, a lead scientist from the MRC Laboratory of Molecular Biology, Cambridge, UK, said, "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."

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," commented Marie-Adele Rajandream, leader of the sequencing component at the Wellcome Trust Sanger Institute. "The chromosomes have an unusual structure, the genome is nearly 80% A and T residues, whereas our genome is 40% As and Ts, and it makes special use of ribosomal genes that is unique to known biology."

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% 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.