A gene that drives speciation in mice has been discovered. Credit: Getty

Geneticists have identified two genes, one in mice and one in fruitflies, that stop the offspring of different species from reproducing — driving the evolution of new species.

A species can be defined as a group of organisms that can interbreed to produce fertile offspring. Hybrid animals, bred from inter-species pairings — such as mules, from the pairing of a male donkey and a female horse — are usually infertile and many such hybrids do not survive. Sometimes, however, pairings of closely related species, or subspecies, produce hybrids with limited fertility.

Identifying the genes that block reproduction in hybrids can reveal the genetic forces that drive speciation. However, fewer than 10 such genes have been identified to date.

Now Jiri Forejt, a geneticist at the Academy of Sciences of the Prague-based Czech Republic, and his colleagues have identified a speciation gene in mice — the first to be found in mammals1.

Tracking down the gene "was terrible work", says Forejt, who has spent the last 30 years trying to identity a suspected speciation gene in two subspecies of mice.

Relying on extensive crossing and genetic modification of animals, and thanks to whole-genome data that has only recently become available, Forejt found that male hybrids of these subspecies are infertile because of the Prdm9 gene.

The finding that Prdm9 encodes a protein that silences genes also confirms suspicions that epigenetic changes — traits that can be inherited without changes to the underlying DNA sequence — are important in speciation.

The fruit of the fruitfly hybrid

"The genetics of speciation are almost by definition inherently problematic — speciation means no crosses, and no crosses means it's very difficult to do genetics," says Nitin Phadnis, a geneticist at the Fred Hutchinson Cancer Research Center in Seattle.

Phadnis and his colleague, H. Allen Orr at Rochester University in New York, were searching for a speciation genes that caused peculiar hybrids when two related subspecies of Drosophila mated. These male hybrids are infertile for most of their lives, but recover some fertility in their old age — but then can produce only daughters.

The existence of these hybrids suggested to Phadnis and Orr that a segregation distorter — a gene that causes chromosomes bearing it to pass more frequently to offspring, in this case by controlling the sex of progeny — might be linked to speciation.

Because segregation distorters can be involved in an arms race with genes that try to prevent such distortion, they may evolve rapidly, says Phadnis. Although it has been proposed that the rapid evolution of 'cheating' genes and their repressors could cause functional divergence between populations resulting in speciation, evidence for this theory has been scarce.

Using similar techniques to the ones Forejt used, however, Phadnis showed that a single gene caused both hybrid sterility and segregation distortion2.

"What this works shows you is that speciation can happen not only because of adaptation to the external environment, but also because of adaptation to the internal genomic environment," Phadnis says.

"Since there are so few speciation genes identified to the sequence level, adding one more to the list is exciting," says Roger Butlin, a geneticist at Sheffield University, UK. "I think there will be a lot more interest in segregation distortion and its relationship to speciation."

Gene bonanza

Both papers are published in Science and could pave the way to the discovery of more speciation genes in the near future. Forejt is already working to identify additional speciation genes that work with Prdm9 to cause infertility in hybrid mice, but says that other researchers are hot on his heels.

"There is no question that in this era of whole-genome sequences and genomic data it is much easier to identify speciation genes than it used to be" says Michael Nachman, who studies mouse genetics at the University of Arizona in Tucson.

With more genes should come greater insight into speciation. Some geneticists wonder whether only particular classes of genes are important in speciation — such as epigenetic genes or segregation distorters — or whether many sorts of genes help to drive species apart.

"What is surprising about the speciation genes that have been identified [so far] is that there is a whole hodgepodge of different kinds of genes with different functions," says Nachman. "I don't think we're going to see [trends] until dozens of genes are identified, and there's just a handful now."