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The Remarkable Mutation Found in Monarch Butterfly

Two research groups have independently found how this iconic insect grew to become resistant to their toxic diet, and they have shown how three genetic mutations are key by making those same modifications in a fruit fly.

Milkweed plants produce compounds known as cardiac glycosides, which disrupt molecular pumps that control the precise of ions flow in and out of cells. Monarch butterflies and other insects that consume the same plant, however, have developed versions of those pumps that leave the animals unaffected. To seek what modifications these milkweed consumers had in common, Noah Whiteman, and his colleagues matched up the gene for this molecular pump in monarchs, including 21 insects, that tolerate the plant to varying degrees.

They discovered three mutations that changed three amino acids within the protein pump. By looking at the distribution of these modifications throughout the insect family tree, Whiteman and colleagues were able to predict which ones came first, and it turned out that the order through which they developed mattered. They then tried to replay the tape of evolution by making mixtures of these changes in fruit flies using the gene-editing tool CRISPR.

A single mutation predicted to have arisen in the monarch’s ancestor made the fruit fly only slightly immune to the toxins in milkweed. However, when that change was combined with a second one, the fruit fly was far better protected, Whiteman and his colleagues publish at present in Nature. And when they continued the third mutation, the fruit fly grew on milkweed as well as monarchs. The flies even retained some of the toxins in their bodies as monarchs do to make themselves toxic to predators. “It’s just mind-blowing that the amazing capability of the butterfly to survive on these harsh chemical compounds comes down to just those 3amino acids in the protein,” Kronforst says.

The findings confirm what evolutionary geneticist Peter Andolfatto of Columbia University and his colleagues reported on 27 August in eLife when they engineered fruit flies with a different editing approach, sometimes making mutations in each copy of the pump’s gene and sometimes making them in only one copy. The order that the mutations were introduced was additionally critical, Andolfatto notes. In a single sequence, the mutations produced healthy, milkweed-tolerant insects. In others, the flies had neurological defects, he and his colleagues reported.

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