Hot clock key to fruit fly’s global spread

Sometimes, survival of the fittest means dependence on weak links.

Widely distributed fruit fly species have a temperature-sensitive step in the manufacture of a key part in their biological clocks. The heat-sensitive stumbling block may be the reason Drosophila melanogaster and Drosophila simulans have been able to spread to temperate zones while their cousins haven’t, a new study in the Dec. 26 Neuron suggests.

Previously, a research team led by molecular biologist Isaac Edery of Rutgers University in Piscataway, N.J., had discovered that, when the temperature rises, Drosophila melanogaster’s production of a major gear in the clock that governs its daily rhythms melts down. The gear, a protein known as PERIOD, helps set the circadian clock in fruit flies and many other animals.

Fruit flies are active in the morning, take a siesta during the hottest part of the day, then wake up and move around again in the early evening when it is cooler. The siesta helps keep the flies from over-heating and drying out. PERIOD protein builds up during the siesta period until it reaches high enough levels to set off the flies’ inner alarm clocks and rouse them for the evening.

“There is a nice association between the time of day that the activity of the fly peaks and the point at which PERIOD peaks,” says Herman Wijnen of the University of Virginia in Charlottesville. Wijnen was not involved in the new study.

Production of PERIOD follows a multi-step process. First, the information contained in the period gene is converted into RNA, which will be read later by the cell’s protein-building machinery. Genes in fruit flies, humans and other eukaryotes contain interruptions, called introns. To deal with these, the cell has a molecular version of TiVo that cuts out introns as if they were commercials interrupting a television program. But cells can’t just skip over introns. The cells must physically cut the interrupting regions out and splice back together the bits of RNA that contain the actual protein-building instructions (called exons.)

In Drosophila melanogaster, and another widely dispersed species of fruit fly called Drosophila simulans, one of the exons contains a weak splice site that doesn’t hold together well when the mercury rises. The weak splice site prevents PERIOD protein from being made when it is too hot, delaying the flies’ evening wake-up call. The heat response allows the two species to vary the length of their midday naps.

That’s important in temperate latitudes in which day length varies considerably across seasons. Flies need longer naps in summer to avoid the heat of the day, and shorter snoozes as temperatures grow cooler and daylight hours dwindle.

But in the new study, Edery and his colleagues show that closely related fruit fly species, Drosophila yakuba and Drosophila santomea, don’t have heat-sensitive splice sites in period. Instead, the two species, found only in Africa, have strong splice sites that hold together even in hot weather, making the schedule of PERIOD production more regular than in the species that are widely dispersed. The equatorial flies also have regimented daily schedules, waking, napping and rousing again about the same time every day. That makes biological sense for species living along the equator where day length and temperatures don’t vary much with seasons, says Edery, who is also a member of the Center for Advanced Biotechnology and Medicine in Piscataway, N.J.

Replacing the weak D. melanogaster splice site with one from the African species also puts D. melanogaster on a regimented schedule, the researchers find.

But a strong splice site that’s insensitive to temperature could spell disaster for a fruit fly that finds itself in northern climates in the middle of summer. The flies might wake from their siesta while it is still hot, and become desiccated as they move about in the heat. The weak, heat-sensitive splice site makes D. melanogaster and D. simulans more flexible and better able to adapt to diverse climates than their cousins, Edery says.

“The proposition that we’re making is that the weak splice sites in melanogaster and simulans species may have facilitated their ability to colonize other parts of the world,” Edery says.

Edery and his colleagues make the argument in “nice” molecular detail, Wijnen says. “It’s a very nice illustration that these mutations seem to be associated with populations [of fruit flies] in temperate zones.”