Genetic Barrier between Species Identified

Hybrid offspring are typically infertile or inviable. Unable to thrive or propagate, they help preserve the differentiation of the species, however unwillingly, unwittingly, or inadvertently. They are made unfit at the molecular level by means of hybrid inviability genes, but these have eluded scientific scrutiny. Some but not all such genes have been found—even in intensely studied fruit fly species. Now, however, scientists based at the University of Utah have announced that they have identified a long-sought hybrid inviability gene that keeps two species of fruit flies from producing viable, fertile offspring.

The find is significant for several reasons. It removes an obstacle form our understanding of the molecular basis of reproductive isolation. It implicates cell cycle regulation in the preservation of species barriers. And it has come to light through the application of a new genomic method, one that could be used to identify hybrid incompatibility genes in other species.

The University of Utah researchers presented their findings December 17 in the journal Science, in an article entitled, “An essential cell cycle regulation gene causes hybrid inviability in Drosophila.” The article’s big surprise is that the inviability gene identified by the scientists is a cell cycle-regulation gene, or cell cycle-checkpoint gene. This gene, called gfzf, is normally involved in stopping cell division and replication if defects are detected. But when mutated and disabled in the new study, the gene allowed the survival of male hybrids of the two fruit fly species.

“We devised a genomic screen, which identified a cell cycle–regulation gene as the cause of male inviability in hybrids resulting from a cross between Drosophila melanogaster and D. simulans,” wrote the authors. “Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males. This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae.”

The gfzf gene evolves quickly, which is what biologists expect from hybrid inviability genes. But is also was a surprise because cell cycle-checkpoint genes usually evolve slowly because they are “conserved” genes essential in most organisms.

That and the discovery that gfzf causes death or infertility in fruit fly hybrids “is really important in cancer biology,” said Nitin Phadnis, Ph.D., University of Utah biologist and first author of the Science article. “Cancer biologists are interested in cell cycle checkpoints because you can get cancer when those go bad [and cells proliferate uncontrolled]. Biologists want to understand the machinery. This work shows that some of those components in the cell cycle policing machinery may be quickly changing.”

Geneticists have sought fruit fly inviability genes ever since 1910, when they first noted hybrids between the two species were dead. During the past decade, other scientists identified and implicated two other genes that play a role in causing dead or infertile offspring when the two fruit fly species mate: a D. simulans gene named Lhr (lethal hybrid rescue) and a D. melanogaster gene named Hmr (hybrid male rescue). If either gene is absent, hybrid males survive. But evidence indicated a third, unknown gene also was required to make hybrids dead or sterile.

“The absence of either Lhr(sim) or Hmr(mel) results in viable hybrid males,” explained the authors. “However, D. melanogaster males that carry transgenic copies of D. simulans Lhr are viable despite carrying both the Hmr(mel) and Lhr(sim) incompatible alleles. These results suggest that the presence of at least one additional unidentified hybrid incompatibility gene is necessary to cause hybrid male inviability.”

Identifying hybrid incompatibility gene is difficult in any case, but the finding gfzf was particularly challenging, in part because the most advanced genetic research tools used for fruit flies were designed for use with D. melanogaster, not D. simulans, which earlier research had indicated as the carrier of an additional hybrid incompatibility gene.

The researchers resorted to figuring out a way to “sidestep traditional barriers,” said Dr. Phadnis, by reversing hybrid incompatibilities between the two fruit fly species and using next-generation sequencing of their genetic blueprints. Dr. Phadnis speculated that the technique used in the current study could be modified and used to investigate other species.

Why would a gene that makes hybrids inviable exist? Shouldn’t natural selection eliminate it over time? Dr. Phadnis said such genes are selected for some other characteristic—researchers don’t yet know what—and “the hybrid’s death is an accidental consequence of that evolution.” Dr. Phadnis speculated gfzf may be favored by natural selection because it helps control so-called jumping genes, which can disrupt essential genes to create disease-causing mutations.

Why is it important to learn how one species can become two new species? “Even when we are little kids, one of the first things we discover about the world is the tremendous number and diversity of species on Earth,” Dr. Phadnis explained. “Speciation is the engine producing that diversity. So understanding speciation has been a longstanding problem, even before the days of Darwin. Now, we finally are able to use technology in creative ways to solve such old, longstanding problems.”