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Utah Researchers Discover Gene that Makes Fruit Fly Hybrids Inviable

NEW YORK (GenomeWeb) – Researchers at the University of Utah have found that a gene involved in cell cycle regulation makes hybrid Drosophila inviable.

Identifying the genes involved in making two species incompatible for mating with each other has been a challenge, the team wrote in its paper in Science today. But the results of this study could lead to a better understanding of how new species form.

"We knew for decades that something like this gene ought to exist, and our approach finally allowed us to identify it," said principal author Nitin Phadnis in a statement. "To understand speciation is to understand how these reproductive barriers evolved. You call them new species when there are barriers that prevent them from breeding with each other. Identifying these genes and uncovering the molecular basis of hybrid sterility or death is key to understanding how new species evolve and remains one of the big and longstanding questions in biology since Darwin."

The team mutagenized 55,000 D. simulans males and bred them with D. melanogaster females. The progeny inherited one mutagenized complement of the D. simulans genome and one intact complement from D. melanogaster. This allowed the researchers to look for mutations in D. simulans genes that may be involved in hybrid incompatibility.

They performed high-throughput sequencing to obtain whole-genome sequences of six of the hybrid flies as well as both parents. They found 600 to 1,200 new mutations among the six flies, but only one gene that was disrupted across all six genomes — a cell-cycle regulator called Suppressor of Killer-of-prune [Su(Kpn)]–glutathione-S-transferase–containing FLYWCH zinc finger protein, which the team referred to as gfzf.

"Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males," the team wrote. "This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae."

The researchers were surprised to find gfzf was the culprit, they said in a statement — it evolves quickly, which is expected of a hybrid inviability gene, but not of a cell-cycle regulator, which usually evolves slowly as it is conserved in most organisms.

They also believe that this finding could be important to understanding cancer biology. "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," Phadnis said in a statement.

The team plans to study what gfzf does at a molecular level and whether there are other genes that make fruit fly hybrids inviable.