How did a group of Neotropical Grass Frogs adapt to prey on chemically-defended toads? If you can believe it, the protein function and molecular evolution sides of the story are just as fascinating as the organismal one. https://www.biorxiv.org/content/10.1101/2020.08.04.234435v2
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In our recent work, we show that an ATPase gene has duplicated in an ancestor of 5 Neotropical Grass Frogs, and that this is textbook neofunctionalization: A division of labor evolved between a resistance-conferring gene (R) and a gene that retained ancestral susceptibility (S).

The R and S gene sequences remained very similar through tens of millions of years, through frequent non-allelic gene conversion (NAGC) that homogenized differences between the R and S paralogs in each species.

You may know this as the villainous “concerted evolution” that can stop neofunctionalization in its tracks… unless, in theory at least, natural selection can save the day by promoting divergence between the gene duplicates.

Enter our hero, natural selection: Hidden in the sequence are little islands of divergence between the duplicates—strongholds that evaded concerted evolution—around 12 amino acid substitutions that distinguish R and S.

Both theory and inference—based on the full R and S sequences across these frog species—suggest that substantial natural selection had to act at these sites to create such islands of “escape” from the hold of frequent gene conversion.

We only know 2 of these 12 substitutions well as associated with a similar toxin resistance, that convergently evolved across many vertebrates.

What about the other 10? We performed protein-engineering experiments that show that the 2 large-effect substitutions confer toxin resistance, whereas the 10 additional amino-acid substitutions mitigate deleterious pleiotropic effects on enzyme function.

Piecing the pieces of this puzzle would not have been possible without a great interdisciplinary team. This work is co-led with @Bufadienolides and @edenling3; orchestrated and directed by @pandolfatto and @CrawfordAJ; and...

together with @santiagoherrer_ , María del Pilar Rodríguez Gómez, Julie Peng, Karen Zhang, Jay Storz and Susanne Dobler.

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