What happens when you end up with an extra genome?

Most of the complex organisms we see around us have equally complex genomes with lots of large gene families that allow them to finely tune the regulation of things like development and metabolism. While some of these extra copies of genes became available when an individual gene got duplicated, a lot of this genetic complexity seems to have arisen when the entire genome was duplicated. In other words, an organism can end up with four sets of every chromosome rather than just one each from mom and dad.

While these copies start out looking extremely similar, evolutionary changes allow individual genes to take on specialized roles or to end up active at different times and locations. This specialization can enable evolutionary novelty—more distinct cell types, more elaborate development, and so on.

It’s estimated that the lineage that led to us vertebrates experienced two separate whole-genome duplications, giving us four sets of some critical developmental genes. The lineage that led to most fish seems to have undergone yet another one since. But all of those events took place in the distant past, leaving lots of questions about how evolution proceeds when there’s extra copies of everything. Now, in order to answer some of those questions, researchers have sequenced the genome of a frog with four sets of chromosomes.

Extra DNA

The frog in question, Xenopus laevis, has been used to study development for many years, starting well before the idea of sequencing a genome became routine. It’s useful because its eggs will develop in water, allowing researchers to manipulate and observe them.

Once researchers tried to start cloning genes from these frogs, it quickly became clear that there were a lot more of them than expected. And it wasn’t unusual to pull out a copy that had been inactivated by mutation. Comparisons with a related species, Xenopus tropicalis, easily revealed why: Xenopus laevis has nearly twice as many chromosomes.

How did that happen? The new genome supports an idea that had been kicking around for a while. About 34 million years ago, the ancestors of Xenopus laevis split off into two separate species. These species evolved separately until some time a bit before 17 million years ago. Then, some of them mated with the wrong species. Since the chromosomes were now rather distinct due to all those years of evolution, they couldn’t pair properly to be separated when the fertilized egg divided. So the chromosomes were copied, but all the copies ended up in the same cell.

The result was a cell that had two sets of near-copies of all its chromosomes. Those could pair up normally during the next cell division, allowing development to proceed. The result turned out to be so successful that it produced two related species with four sets of chromosomes. To confuse matters, however, both of the two ancestral species—we’ll call them A and B—that produced Xenopus laevis now seem to be extinct.

How did the authors figure this out? It turns out that at some point in the past, both A and B picked up a sort of DNA-level parasite called a transposable element, which inserts itself into the genome at random. Conveniently, however, they picked up different transposable elements, which can now be used as tags for the sets of chromosomes each species passed on to Xenopus laevis. For reasons that aren’t clear, the two sets of chromosomes haven’t exchanged much DNA, which allows the people who sequenced its genome to study what happened to these chromosome sets separately.

Evolution in action

Immediately after the extra set of chromosomes appeared in these frogs, they faced a rather unusual situation: they had an entire set of extra genes that were entirely superfluous to making a frog. If evolution were to ruthlessly purge superfluous DNA, most of these extra copies would be long gone 17 million years later. But evolution is a messy process, and it tends to allow a lot of junk to linger in our genomes. In these frogs, over half the duplicated genes are still around.

Many of the genes that have gone missing have simply been deleted, along with stretches of the DNA nearby. These sorts of deletions occur at random over time, and apparently many of them stuck around. That’s presumably because losing the gene either did no harm or provided a small benefit. A number of other genes have picked up mutations that inactivated them, while still others appear intact but don’t seem to be active at any point that the researchers could identify. Oddly, genes have been lost from the B set of chromosomes at nearly four times the rate than they’ve been lost from A’s.