Originally posted on sciy.org by Ron Anastasia on Thu 10 May 2007 01:44 PM PDT
Newly-completed possum genome gives perspective on mammals
By John Timmer | Published: May 09, 2007 - 12:47PM CT
The cute critter on the right is not a rat, despite the apparent
similarities. Instead, it's South America's own short-tailed opossum,
or Monodelphis domestica
as it's known in scientific circles. Because of its small size and
ability to breed in captivity, the animal has become the lab rat of
those who pursue biological studies of marsupials. As a result, it was
the first marsupial to have its genome sequenced. The genome is already
available online, and an analysis appears in the latest issue of Nature.
A marsupial genome provides some important perspective for humans, which fall into the group of placental mammals, or eutherians. Prior to the Monodelphis genome, the only mammals sequenced were all placentals. The most closely related species with a genome done that could serve as an outgroup for evolutionary comparisons was the chicken; we haven't shared a common ancestor with birds for about 310 million years, only 50 million years or so after fish started crawling out of the water. Marsupials shared a common ancestor with mammals only 180 million years ago, making them a much better point of comparison for understanding placental genomes, including the human genome.
Monodelphis has a large genome, about 0.3 Gigabases larger than the human genome. It's distributed among only eight chromosomes, though, with the smallest of them being larger than the biggest human chromosome. With the new information and five eutherian genomes available, the researchers were able to piece together what the chromosomes of the last ancestor of this branch of the mammals likely looked like.
The genome itself, like that of most of the rest of mammals, appears to be largely junk, with over half of it composed of the remains of transposable elements. In terms of the genes, the collection is nearly identical to those in the human genome, and most of the differences between genes do not change the proteins that they code for. Once clear equivalents and extra copies are eliminated, only about 624 genes (out of over 18,000) appear unique to the opossum. Most of these appear to be fragments or nonfunctional, leaving only eight genes that appear functional and marsupial-specific. From the human perspective, there are about 500 unique genes, but most of these involve duplications of existing genes that are specific to the human lineage.
What are all these lineage-specific duplications doing? For the marsupial, many appear to be involved in sensory perception, such as the visual system, taste, and smell, including pheromone receptors. There are also adaptations for diet and detoxifying compounds that arrive with the food. As with most animals, changes to the immune system play a key role. The marsupials have a unique T-cell receptor that's expressed early in development; it's tempting to speculate that this plays a role during its time in the mother's pouch.
With most of the genes being largely the same, how come Monodelphis is so different? As with the rest of the mammals, the differences appear to arise from how the genes are controlled. The sequences that determine when and where a gene is expressed have a number of key differences.
This control can be large scale. Both marsupials and eutherians inactivate one of the female's two X chromosomes in order to keep the dose of its genes equivalent to that from the male's single copy. Both groups appear to have a system in which the male X arrives in the fertilized egg inactive. Mammals have a second system on top of that: early in development, the male X is reactivated, then an X is chosen at random for deactivation. Monodelphis lacks this second system, and retains what is probably the ancestral state: the male X stays inactive throughout its life.
As far as individual control elements, two clear patterns emerge. One is that evolution has stuck with what works. Of the non-protein-coding sequences that had previously been identified as conserved between chickens and mammals, nearly 99 percent showed up in the marsupial genome.
The second is that novelty has arrived by adding new control elements (called enhancers) on top of this common set. The marsupial genome suggests that nearly 20 percent of functional enhancer elements identified in some experiments in human cells may be unique to eutherians. Focusing specifically on developmental genes, the rate rises to nearly 20 percent. Thus, the big differences appear to arise from new features in the expression of genes, rather than due to changes in the proteins they code for.
Incidentally, in past coverage, we've noted that many of the new gene regulatory sequences may be derived from transposons. The new data suggests that's simply an artifact of half the genome being composed of transposons. The authors found that their ability to identify identical transposon sequences and the rate at which new enhancers appeared to be derived from transposons were essentially identical.
As always, the researchers want more data. They suggest it will be much easier to draw conclusions about mammalian evolution once the cousins of Monodelphis from Australia and North America have their genomes completed as well. Given the current capacity of the world's genome centers, I'm sure that's just a matter of time.
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