Genes of Flies Permanently Adjust to Oxygen Deprivation

Nicole Oliver/UCSD Guardian

Prolonged exposure to environments with low oxygen levels, such as mountain ranges, can lead to permanent changes in your genes. Researchers discovered that flies under hypoxia (a shortage of oxygen) underwent permanent genomic changes.

In the study, UCSD researchers experimented on the fruit fly Drosophila melanogaster — a species with cellular mechanisms similar to humans’ — and tested the impact of hypoxia on their genes. They found that it causes permanent changes that were then passed down generations.

“The hypoxia-adapted flies passed the tolerance trait from generation to generation,” Division of Genome Information Sciences head Kelly Frazer said. “The trait persists even in the absence of hypoxic stress [such as] when they were exposed to normal oxygen levels. [This suggested] a genetic rather than physiological adaptation,” Frazer worked with School of Medicine professors Gabriel Haddad and Dan Zhou, who conducted the study. Haddad and Zhou began investigating the causes of flies’ ability to survive under constant hypoxia in 2005. The researchers split a population of fruit flies and bred them over 200 generations.

Frazer’s team bred the control population under normal oxygen levels, or about 21 percent. The other population was kept at a lethal oxygen level of 4 percent.

The gene expressions of the two sets of flies were compared to determine whether their ability to adapt was due to genetics or mere physiology.

Using high through-put screening — a process which allowed researchers to identify any genome variations — the researchers were able to identify specific regions on the X and 3R chromosomes that contained mutations.

“If [these] mutations cause a fly to survive in low oxygen better, then flies who have this mutation would be more likely to have offspring than those who do not have the mutation,” biology graduate student Nitin Udpa, who analyzed the genome sequencing, said.

“If you run the experiment over several generations, classical genetics suggests that this advantage would keep propagating until every individual in the population has the mutation,” Udpa said.

Analysis of the genes shows that the mutations were present in a cell signaling pathways, which are also present among many mammals, including humans. The findings strongly suggest that humans who can survive under decreased oxygen levels may also have similar genetic mutations.

“The next step is to perform similar types of genomic studies in humans.,” Frazer said. “The whole genome-sequencing costs have dropped significantly. We can start analyzing populations of individuals that live at high altitudes for evidence of adaptation to hypoxic conditions in the human genome.”

Hypoxia doesn’t only affect those living at high altitudes. Strokes, heart attacks, neonatal diseases and cancer can also decrease oxygen flow to tissues.

“Since much of the [Notch] pathway is also present in humans, this could provide a lead in determining a mechanism for hypoxia responses in humans,” Udpa said.

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