Evolvability: A Good Design Principle

Evolvability: A Good Design Principle

by Katie Galloway

Your computer’s newest antivirus probably comes with live updates so it can arm itself against the latest trojan-phishing-spyware attack. It may not stop you from doing silly things like sending your bank information to that lovely man from the British lottery that just happens to want to give you a million dollars, but hopefully it will neutralize other less obvious threats. The antivirus protection works well because teams of people constantly update the database with signatures of the latest threats so your software is prepared. Internet threats adapt very fast so good antivirus software must evolve as quickly or your computer system might not survive. The same principle applies to biological systems and their survival programs.

In Earth’s highly dynamic environment, survival requires that biological systems swiftly yield solutions to new threats. Enzymes, known as biology’s workhorses, perform a variety of cellular functions such as harvesting energy, degrading toxins, and assembling new proteins. Organisms like bacteria can live in highly variable settings that offer ever-changing challenges, including the introduction of a new predator, toxin, or energy source. To survive and compete in such surroundings, organisms require highly flexible enzymes that can quickly adapt (which is the intended use of “evolve” throughout this article) to take advantage of environmental variation. Evolving latent, promiscuous (or secondary) functions allows biological systems to rapidly respond to environmental fluctuations.

Promiscuous functions permit enzymes to perform catalysis on more than one type of molecule. Usually, enzymes are specified for certain molecules or types of molecules called substrates. When scientists discover an enzyme that catalyzes reactions with unexpected molecules, the enzyme is said to have promiscuous catalytic activity.

As an example of this activity, consider using a shoe as a hammer. Even though the shoe is clearly meant and designed for a different purpose it can still be semi-useful in a bind. Similarly, biological systems appropriate their enzymes for unusual tasks. Sometimes these functions eventually become necessary for the survival of an organism. In these cases, the enzyme can undergo molecular evolution to become dedicated and specialized to its promiscuous function. One notable example is the organophosphate hydrolases (OPH).

Organophosphates are man-made esters (a large class of organic compounds often used in fragrances) of phosphoric acid introduced into the environment as insecticides and nerve gases within the last few decades. Yet scientists have already discovered an enzyme in bacteria called phosphotriesterase (PTE) that hydrolyzes (breaks down) the organophosphate paraoxon with great efficiency. The fact that PTE exists to breakdown a recently introduced and previously completely foreign type of molecule is unexpected. One hypothesis that explains this is the existence of promiscuous activity in existing natural enzymes.

Researchers suspect that this rapid adaptation can be accounted for by the existence of promiscuous functions in enzymes called esterases. Esterases hydrolyze their unique type of esters; in other words, they specifically break particular esters apart with the help of water. The activity of these esterases on new substrates is initially weak, but scientists theorize that the advantage conferred by rare beneficial mutations accelerates the spread of the mutation throughout the population and allows the enzyme to increase its ability to hydrolyze the novel substrate.

Through in vitro evolution laboratory techniques, researchers simulated the evolution of an esterase into an efficient OPH.1 Starting with an esterase that demonstrated slight promiscuous activity as an OPH, researchers mutated the sequence into a library of variants and screened for those with increased ability to hydrolyze the organophosphate paraoxon. Through multiple rounds of in vitro evolution, the OPH activity was increased 10- to150-fold over the native enzyme. Additionally, researchers demonstrated that activity for non-native substrates can increase without destroying activity for the native substrate. Theoretically, this allows the cell to benefit from the new function while retaining the old.

Just like smart engineers who create software that can evolve to the changing demands of users, God has built proteins to be evolvable to satisfy the changing conditions of life. Evolvability is a good design principle because it affords biological systems the robustness and flexibility to adapt to new challenges while maintaining essential cellular processes.

Additionally, by allowing organisms such as bacteria the latitude to evolve new functions from existing proteins, bacteria can maintain smaller, more efficient genomes while responding to novel situations. Furthermore, development of these new functions creates the potential for remedying man-made ecological disasters such as the spread of organophosphates into drinking water.

A good engineer chooses the appropriate materials to fulfill his purposes. In a similar way, this scientific research points to a Creator who has demonstrated purposefulness by choosing to build life out of highly evolvable materials.

  1. A. Aharoni et al., “The ‘evolvability’ of promiscuous protein functions,” Nature Genetics 37, no. 1 (2005): 73-6.