Positive Selection of Tyrosine Loss in Metazoan Evolution (Science, Sept 2009): Protein diversity can select for changes in DNA

Some terms:
Phosphorylation:  Proteins are made up of chains of amino acids. Though there are 20 essential amino acids, only three are likely to have a phosphate group added to it: serine (S), threonine (T), or tyrosine (Y). The addition of the phosphate group can have profound changes on a protein's structure, function, and interactions with other proteins. For example, certain phosphorylations will change the shape of a protein such that one part blocks the function of another part; this is called auto-inhibition. Other phosphorylations activate whole proteins, waking them up from an inactive slumber. Yet other phosphorylations are bound by phosphate-binding proteins, which can alter the location of the bound protein or bring it closer to other proteins that it can interact with.

Kinase: A kinase is an enzyme (which itself is a protein) that phosphorylates another protein. Kinases, particularly tyrosine kinases tend to play essential roles in cells, including ones that prevent or accelerate cancer. Now, the thing is, kinases are very specific: they don't just add phosphates to any old protein. Any one particular tyrosine kinase, say, Cdk1, only phosphorylates a small number of certain sites on certain proteins, even though the number of such target sites in total numbers in the many hundreds. This tends to be fairly well conserved between and among different species.

 

The basic results: The researchers looked through 16 different species, from yeast through worms and flies up to cows and humans, and counted the total number of tyrosines found in all of the different proteins encoded for by the genome. As a measure of organismal complexity, they also counted the number of different cell types in the organisms, with yeast at one and humans topping out at 160+. What they discovered was that the total number of tyrosines decreased (from 3.4% of all amino acids down to 2.6%) as multicellular complexity increased. In other words, the more complex the creature, the less it wants to have tyrosines around in its protein repertoire.

The reasoning goes like this: as evolution proceeds, new tyrosine kinases come about through gene duplication events and subsequent diversion. These new tyrosine kinases are a little bit different from their predecessors, so they're likely to phosphorylate a new set of tyrosines. At the same time, other new proteins are evolving as well, so both old and new tyrosine kinases have to decide, in a way, whether or not to phosphorylate the tyrosines on these new proteins as well. The whole thing can get a little confusing for the cell, not knowing ahead of time whether or not it's good to phosphorylate this tyrosine or that one.

So, it goes through natural selection on this microscopic scale. Most newly phosphorylated tyrosines will usually throw the cell's carefully structured phospho-network out of balance, and even if they don't directly detriment the cell, the chaotic nature of too many tyrosine phosphorylation sites can get messy. The answer that evolution came up with was to get rid of too many tyrosines. This decrease means a little more simplicity in the total system, which should mean better fitness. Indeed, the total number of tyrosines also decreases as the total number of different tyrosine kinases increases. Fewer targets, more controllers, better control.

What this means for evolution: This is evolution writ large at both the microscopic and macroscopic levels. The DNA of the genome changes in response to the proteins surrounding it - a dynamic back-and-forth played out over millions of years across many, if not all species. It's not simply that less complex systems have less complex controls. It's that we can follow the ups and downs of the tyrosine kinase family by examining the tracks it has left behind in the DNA which encodes the entire body of real and potential target proteins. Phosphorylation is such a fundamental and powerful force in normal eukaryotic cellular processes - the mutation of a single kinase such as Ras can lead to unbridled cancer - that its power is also felt through evolutionary time.