Someone Teach Ann Gauger to Google

Over at the blog of the Biologic Institute (the Discovery Institute's science-y wing), Ann Gauger has been writing regularly about molecules. Her April 30th post, Intricate Coordination, looked at the enzyme carbamoyl phosphate synthetase (CPS). Wow! CPS is complicated! It has two parts, three active sites, and an intramolecular tunnel. And here is Ann's take-away message:

How does a neo-Darwinian process evolve an enzyme like this? Even if enzymes that carried out the various partial reactions could have evolved separately, the coordination and combining of those domains into one huge enzyme is a feat of engineering beyond anything we can do. 

Well, how do we explain this?

First, by understanding that CPS is not a singular 'thing'. Like any biomolecule of any size, it comes in a variety of shapes and sizes throughout the different species of life. In fact, CPS performs an important role in the cell, and is therefore found across Bacteria, Archaea, and Eukarya. We can use CPS to draw a phylogeny, a tree of life. So the first part of an answer to Ann is yes, CPS does evolve. Evolution is the simplest explanation of the many versions of CPS found throughout living species.

Second, we can see that Ann's question is really a sense-of-wonder question. Parts, sites, a tunnel, a  lab under an extinct volcano, sharks with lasers, it is all so amazing. Yes, it is, even if it doesn't have those last two items. But "substrate channeling", as the cool kids call it, isn't unique to CPS. Lots of enzymes do it. Sometimes they use a tunnel of hydrophobic residues, sometimes hydrophillic residues. Sometimes the 'tunnel' is more of a path of favorable charges across the surface of the enzyme, sometimes it is a floppy arm that carries substrates from one place to another as it flops around. Not only has it evolved, it has evolved multiple times for different substrates.

These different functional mechanisms help to keep reactants from floating off into the cytoplasm, thereby increasing the speed and efficiency of an enzyme. AA residues facing into the tunnel can effect the speed with which molecules diffuse down its length, keeping the different parts of the reaction in sync. These qualify as huge selective pressures, so the second part of an answer to Ann is that evolution created these enzymes using the standard preference for higher functioning processes. Natural selection, you've heard of it, right?

Thirdly, we can understand the question to be one of, 'from what functional predecessor did CPS evolve?" If we look at CPS across the various species, it comes in two parts with separate functions, so right there we can see that these parts could have evolved separately, from less specialized or efficient predecessors. The larger of the two subunits, the part with two active sites, seems to have undergone a gene duplication event very early in its history. This subunit seems to have developed from a carbamate-kinase ancestor.

Putting it together, an answer to Ann's question is "Yes, CPS does evolve, by normal functional selection, from clear ancestors via well understood variational events."

"... a feat of engineering beyond anything we can do"? Ummm, no. Looking at the phylogeny, pretty much any branch is a sequence of exaptations, duplications, fusions, mutations, wash, rinse, repeat. Yeah, we can do that. As a matter of fact, we do do that. We've been poking at CPS for a while, pulling the genes apart, putting them back together, mutating it. It is the basic path to understanding how CPS works.

Now I will make a confession. I am not a biochemist or an evolutionary molecular biologist. But I do know how to use Google. Starting from "evolution carbamoyl phosphate synthetase" and ending with "evolution substrate channeling" I learned a lot about CPS very quickly, mostly with the help of papers published in the 1990's. Google is your friend. PubMed is your friend. 

Friends don't let friends blog stupid. Don't follow the path of Cornelius Hunter, he of the "Stuff's Complicated, Must Be Jeeebus" blog tic. Think about it, Ann.