Ancestral sequence reconstruction relies on phylogeny and statistics to infer the most likely amino acid
Scientists collect sequences from databanks of the modern versions of the protein of interest from different organisms.
Computer algorithms construct a phylogenetic tree for the proteins (Curr Opin Struct Biol, 38:37–43, 2016).
The programs can then infer the sequences that likely existed at nodes of the tree, before the modern species evolved.
Finally, the scientists order synthetic DNA and generate those proteins in the lab to use for experiments.
One way to ensure that an ASR protein behaves like the true ancestor is to resurrect and test not only the best amino acid sequence generated by the algorithms, but a few proteins with the second-best guesses, or third-best guesses, and so on. If those alternative ancestors act like the best-guess version, then researchers figure the conclusions are probably robust. Recently, evolutionary synthetic biologist Eric Gaucher ...
