BioWorld International Correspondent
LONDON - The humble slime mold has the potential to be useful in studying human diseases. An international consortium of scientists has just finished sequencing its genome, and has discovered that more than 60 of its genes are similar to genes known to cause human disease.
Now that its genetic blueprint is known, research into the slime mold - a type of amoeba that lives in the forest floor, hunting down bacteria and, when food is short, aggregating into a mobile slug that produces a fruiting body - is about to undergo an explosion, the researchers who carried out the work predicted. It is more accurately described as the social amoeba Dictyostelium discoideum.
Paul Dear, group leader at the Laboratory of Molecular Biology in Cambridge, UK, told BioWorld International: "Most of the other model organisms, such as the fruit fly and the mouse, will share genes with humans that correspond to human disease genes, but the great advantage to Dictyostelium is that it is simple and easy to manipulate in the laboratory, while retaining much of the complexity of human cells."
The list of Dictyostelium genes that are related to human diseases includes genes known to play a role in colon cancer, and many causing neurological diseases, including Tay-Sachs disease, amyotrophic lateral sclerosis, and Parkinson's disease.
Dear said: "It will now be easy for scientists to look up the gene they are interested in on the internet, knock it out in Dictyostelium and see what happens to the cells. This will give them an indication of how the loss of the gene in question affects human cells."
The genome is published in the May 5, 2005, issue of Nature in a paper titled "The genome of the social amoeba Dictyostelium discoideum."
An international consortium, with teams in the UK, Germany, the U.S., Japan and France, undertook the project.
Speaking on their behalf, Dear said: "This is one of the most important genomes to be sequenced over the past couple of years. It fills in a huge gap in our genomic survey of all organisms. We've got plant genomes, mammalian genomes, insect genomes and fungal genomes, but this is the first member of the branch of life that includes the amoebae to be sequenced."
It is important in evolutionary terms. Eukaryotes split early into plants and other organisms, and amoebae sit on a branch that emerged very soon after that split. The authors wrote in Nature that the amoebozoa are "noteworthy as representing one of the earliest branches from the last common ancestor of all eukaryotes."
Given that ancient position on the evolutionary tree, the consortium members were surprised to find that the genome Dictyostelium appeared to encode more than 12,000 proteins - about half the number that humans have.
Many of those proteins contain huge sections of repeated amino acid sequences, more than any other organism sequenced so far. Dear said: "It is a complete mystery why these repeats are there, and how Dictyostelium manages to tolerate them. In human cells, such repeats tend to be problematic; for example, in Huntingdon's disease, the protein huntingtin contains a similar stretch of repeated amino acids, and when this lengthens, it leads to disease."
Many antibiotics produced by soil bacteria are manufactured by polyketide synthases. Analysis of the genome of Dictyostelium suggested that it contains more than 40 genes encoding polyketide synthases. By contrast, the yeast Saccharomyces cerevisiae has no polyketide synthases. Dictyostelium also has a type of polyketide synthase typically found in higher plants.
Dear said, "The rich repertoire of those important molecules certainly warrants further investigation in the search for new antibiotic and antiparasitic compounds."
The type of movement used by Dictyostelium is similar to that shown by human white blood cells. That explains why the amoebae have been used in the past to study the cellular cytoskeleton and its role in cell movement. The genome of Dictyostelium reflects the importance of movement in its lifestyle: Its genes encode an "astonishing assortment" of proteins used to control the cytoskeleton, said the authors, as well as tens of genes encoding either actin or related proteins, or proteins that bind to actin.