May 10 2007
Study of the DNA of a South American marsupial called the opossum has revealed that a gene's location influences whether or not it is likely to gather changes that could lead to disease.
The researchers focused on gene location within DNA when it is packaged into chromosomes, the protective carrier for DNA.
Monodelphis domestica, the opossum and scientist share 69% of their genes. Image courtesy of Nicolas Gouin.
The opossum, a relative of kangaroos and koalas, packs almost the same number of genes into nine pairs of huge chromosomes that humans spread out over 23 smaller pairs, making the two species ideal for comparison.
Scientists discovered that genes located deep within a chromosome gather changes that could lead to disease more quickly than those found close to the chromosomal edge. Natural selection tends to remove mutations that are potentially harmful and this research result shows that it works least effectively towards the inside of large chromosomes as opposed to the ends.
The research, led by Dr Leo Goodstadt and Professor Chris Ponting of the Medical Research Council Functional Genetics Unit at Oxford University is published in Genome Research . It is part of a wider international collaboration to compare the marsupial and human genomes published in Nature .
Scientists have long puzzled over whether genes found on big chromosomes are any different from those on small chromosomes in other species, and whether having many or comparatively few chromosomes is advantageous for a mammal in any way. These research findings suggest that a real advantage is conferred by gene location.
When the scientists scrutinised the opossum's DNA they discovered that genes situated near the edge of a chromosome were better at discarding mutations that might otherwise lead to disease.
“Evolution has been pretty good at getting rid of mutations when they're near the edges of chromosomes, but rather poor at doing so in their middles, because genes that lie in the middle of chromosomes are less likely to be shuffled before being passed on to the next generation”, says Professor Ponting. “It really is all about location; where a gene lives matters. This discovery is important because it will help us to separate DNA changes in the human genome that lead to disease from those that don't.”
The research team also found that 69% of opossum and human genes were present as single genes in the species' common ancestor 180 million years ago, and that it is genes involved in immune defence, reproduction or adaptation to new diets that evolve faster than any others.
Dr Goodstadt explains:
“All mammals could be described as being in an arms race. They are always fighting off parasites and disease in a competition to see which can breed and survive to produce the next generation. For example, immunity genes can't stay still even for a single moment. The opossum genome has shown us that it is genes involved in immunity that change most rapidly. This is important in giving us extra options in tackling diseases that affect people. Observing how genes in other species have successfully dealt with parasites and bacteria could suggest new ways to approach development of therapies to battle human infections.”
Original research paper: An analysis of the Gene Complement of a Marsupial, Monodelphis domestica: evolution of lineage-specific genes and giant chromosomes is published in Genome Research on 10 th May 2007.
The results described in this research paper and corresponding press release contribute to work by an international consortium of scientists that is also published this week in Nature, paper title: Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences.
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