I was reading an informative article in the journal Science, This protein designer aims to revolutionize medicines and materials, on work done by Baker, a protein scientist who has been able to develop a method to predict the three dimensional protein structures from the primary sequence of amino acids.

Proteins are  large molecules made from a chain of amino acids of which there are 20 different types of amino acids found in nature. DNA contains genes (sequences of nucleic acids) which code for a sequence of amino acids which makes proteins. Mutations in DNA cause changes in proteins. Evolution claims random mutations will on rare occasions change an existing gene into a new functional gene which equates to turning an existing protein into a new protein with a new function such as catalyzing a different reaction. In order for new life forms; biological change must at the simplest level begin with the evolution of proteins.

The article explains:

protein folding_sciencemag
Schematic diagram illustrating importance of amino acid pairs in proteins. Source: V.Altounian/Science

“Comparing the DNA of similar proteins from different organisms shows that certain pairs of amino acids evolve in tandem—when one changes, so does the other. This suggests they are neighbors in the folded protein, a clue for predicting structure.Sander reasoned that the juxtaposition of those amino acids must be crucial to a protein’s function. If a mutation occurs, changing one of the amino acids so that it no longer interacts with its partner, the protein might no longer work, and the organism could suffer or die. But if both neighboring amino acids are mutated at the same time, they might continue to interact, and the protein might work as well or even better.”

The article says that they discovered that evolving protein A into protein B would often require a pair of mutations. If only one mutation is made without the other then the protein will not function and natural selection will eliminate it. In order for a fitness or function to be conferred, it must be undergo at least two coordinated mutations. Although the article is brilliant in explaining how protein structure works it simply assumes that random mutations can actually coevolve a pair of mutations to produce a new protein.

Fortunately others have not assumed this but actually calculated how long it would take for a new protein that requires two coordinated mutations before being selected to arise in the human population for example.

Durett and Schmidt calculated how long it would take for a new functional protein to arise in a by random mutations which first inactivated the existing binding site in a protein and then secondly activated a new binding site. Their model was specifically for populations similar to humans.“…we examine the waiting time for a pair of mutations, the first of which inactivates an existing transcription factor binding site and the second of which creates a new one”

 Their results indicate that mutations that require two coordinated mutations in a human population with an effective population size of 10,000 would take 216 million years. Recall that evolution claims that humans diverged from their common ancestor with chimps 6 million years ago.

“We now show that two coordinated changes that turn off one regulatory sequence and turn on another without either mutant becoming fixed are unlikely to occur in the human population…Multiplying by 25 years per generation gives 216 million years…Multiplying by 0.75 reduces the mean waiting time to 162 million years, still a very long time. Our previous work has shown that, in humans, a new transcription factor binding site can be created by a single mutation in an average of 60,000 years, but, as our new results show, a coordinated pair of mutations that first inactivates a binding site and then creates a new one is very unlikely to occur on a reasonable timescale.”

They conclude a coordinated pair of mutations cannot occur in the human population because it would take 162 million years. And yet the article from Science states “The upshot, Sander proposed, was that certain pairs of amino acids necessary to a protein’s structure would likely evolve together”, which is simply an assumption that it is likely that a pair of co ordinated mutations would evolve together. Durett and Schmidt show it is a false assumption.

This poses a huge problem for evolution:

  1. Protein structure and research shows that most novel proteins require at least a coordinated pair of mutations to be stable and functional.
  2. Population genetics calculations demonstrate that novel proteins requiring a coordinated pair of mutations are not going to occur in small populations like humans with long generation times in a reasonable time.
  3. Therefore natural selection acting on random mutations cannot produce novel proteins and new biological change in  populations similar to humans within a reasonable time.


  1. Rick Durrett, Deena Schmidt. Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution.  GENETICS November 1, 2008 vol. 180 no. 3, 1501-1509; DOI: 10.1534/genetics.107.082610