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single blind cavefish, white against black background

 

Blind cavefish have evolved to be starvation resistant, constantly hungry, and fat but healthy. Interestingly, the genetic mutations that contribute to these characteristics also have been found in the genomes of some obese humans.

Blind cavefish that have adapted to annual cycles of starvation and binge eating have mutations in the gene MC4R, the same gene that is mutated in certain obese people with insatiable appetites, according to a study led by HMS geneticists.

The findings, published online July 13 in PNAS, reveal more about how vertebrates evolved to have different metabolisms and could provide insights into the relationship between human obesity and disease.

“We know that people have different metabolisms that lead to their gaining weight with different amounts of eating,” says the study’s senior author, Clifford Tabin, the George Jacob and Jacqueline Hazel Leder Professor of Genetics and chair of the Department of Genetics at HMS.

Blind cavefish in the study live in dark, nutrient-poor caves in northeastern Mexico. In the hundreds of thousands of years since they were separated from their surface-dwelling cousins, they have adapted to their harsh environment by gradually losing their eyes and their pigmentation and by becoming resistant to starvation. Cavefish achieve the latter by storing massive amounts of fat and by burning it slowly.

The researchers found that after two months without food, the cavefish lost half as much weight as comparable surface populations.

How did the cavefish become so obese in the first place? The scientists found that some cavefish populations evolved to have insatiable appetites; when food does become available, as when it is swept in by annual cycles of high water, the fish eat without limit and store enough fat to sustain them until the next feast. Remarkably, the cavefish live long, healthy lives despite being so overweight.

The team analyzed the DNA of fish from several different caves as well as from those in the surrounding surface rivers to determine what genetic mutations could drive the differences in metabolism, body weight, and appetite.

They found that most of the cavefish had mutations in MC4R, a gene regulated by leptin, an appetite-suppressing hormone, and by insulin. In humans, MC4R mutations—including one that is identical to one in some of the cavefish—are the most common single-gene cause of inherited obesity.

In cavefish, say the team, the mutations appear to reduce the gene’s activity by taking the brakes off their appetite suppressor. Although this can be disastrous for humans—children with MC4R mutations can’t stop eating—the mutations have proven advantageous for the fish.

The researchers are certain other genes are at play in the cavefish and are now looking for additional mutations in the fish, which could in turn inform the search for genes that influence human metabolism and obesity.

Photo: Dante Fenolio/Science Source

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Voices
Autumn 2015

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genetics

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