Evolution and Immunity: Same Story?

"The BioLogos Forum" frequently features essays from The BioLogos Foundation's leaders and Senior Fellows. Please note the views expressed here are those of the author, not necessarily of The BioLogos Foundation. You can read more about what we believe here.

Today's entry was written by Kathryn Applegate. Kathryn Applegate is Program Director at The BioLogos Foundation. She received her PhD in computational cell biology at The Scripps Research Institute in La Jolla, Calif. At Scripps, she developed computer vision software tools for analyzing the cell's infrastructure, the cytoskeleton.

I’ve had ample opportunity this week to reflect on God’s goodness in providing me a working immune system; I’m nearing the end (hopefully) of a bad cold. Normally I would bewail the havoc caused by the virus itself, but after writing my last post on how antibody diversity is generated, I have become increasingly grateful for this life-protecting process.

Antibody fine-tuning

At this moment, millions of B cells are patrolling my spleen and lymph nodes, each sporting a different antibody on its surface. If a foreign molecule from the cold virus happens to stick to an antibody on a particular B cell, the cell can get “activated.”

Pathogens are like cockroaches. If you see one roach, you can bet there are many more lurking under cupboards and between walls. Just as one shoe won’t kill them all, one B cell can’t make enough antibodies to deal with an infection. Activation causes the B cell to reproduce, creating more and more B cells that can produce the same kind of antibody.

As is typical during cell division, most of the DNA in dividing B cells is copied with extremely high accuracy. But in the gene segments coding for the variable region of the antibody, mutations accumulate about a million times more often than normal. Why would this be? Isn’t the point of B cell replication to make more identical antibodies?

Almost. It turns out that these frequent random mutations contribute to optimize the antibody. A shopping story helps to illustrate. I was recently at the mall and found a fabulous pair of shoes on sale. Sadly they were out of my size, but it was such a good sale that I decided to buy the half-size down, figuring the shoes might stretch out a little and grow more comfortable with time. Bad idea! That great bargain turned out to be pretty expensive when I got blisters and never wore the shoes again. Clearly this was not an optimized choice.

Just because you can get your foot into a shoe does not mean it fits. Likewise, just because an antibody binds to an antigen does not mean the two are perfectly complementary. Descendents of the activated B cell have a mechanism to induce mutations so each one can make a slightly different version of the antibody. If one of the resulting B cells makes a better-fitting antibody than its kin, it will have a selective advantage and proliferate. The other cells will not become activated as often and will end up dying by apoptosis, a kind of cellular suicide. This mechanism of mutation and selection, called affinity maturation, produces a highly specific, strong interaction between the antigen and the antibody.

Antibody production and evolution both involve mutation and selection

I believe God is sovereign over all of creation, but I don’t imagine he is presently curing my cold by directly controlling the specific gene rearrangements and optimizing mutations in each of the millions of B cells in my body. Could he do so? Of course! But if that were the case, why bother making billions of antibodies in the first place? The evidence suggests that God has chosen to work through a random process, one which involves the routine creation and destruction of millions of cells that never get used. This is the ordinary means by which God maintains our health. The miracles of healing recorded in the Bible are miraculous precisely because they don’t occur by this normal, natural process.

In my last post, I stated that the generation of antibody diversity is an example in which God uses a “blind” system to sustain and preserve life. I then suggested a link to evolution by asking, “If God uses natural mechanisms that work over short time scales (less than a week) to evolve life-giving solutions to disease, could he also use a similarly elegant approach to create life over long periods of time?”

Some may argue that a small-scale process like antibody production isn’t comparable to the processes of mutation and natural selection that are supposed to have caused macro-evolution. Intelligent Design proponent Michael Behe, for example, accepts that all creatures (including humans) have a common ancestor, but he believes random mutations are not powerful enough to have brought about the diversity of life we see today. He argues that there is an “edge” of evolution: mutation can bring about drug resistance and other small-scale adaptations, but beyond a certain point it can’t really produce anything new.

Clearly, antibody production creates something new: the random recombining of whole gene segments generates highly specific, never-before-seen protein functionality within just a few days. The body can respond to any foreign entity, simply by sorting through billions of ready-made possibilities. Furthermore, a pretty-good solution can be made even better by generating many variations on a theme and sorting through these for the optimal antibody.

Evolution works by the same kinds of mechanisms, except the mutations occur in germ cells (which give rise to egg and sperm) rather than in B cells, and the sorting (selection) process occurs at the population level rather than the cellular level.

Though often neutral or destructive, mutations sometimes create new functionality

Most people are familiar with point mutations, in which a single DNA “letter,” or base, gets changed. However, mutations come in several other varieties. Short sequences of DNA can be inserted or deleted at random. Chunks of DNA can get cut out and inserted in the opposite direction. Individual genes or even whole chromosomes can get lost or duplicated. In rare cases, the entire genome can get duplicated!

The effect of a mutation principally depends on where it occurs, not on the size of the DNA segment affected. A large deletion occurring within a long stretch between two genes may do nothing at all. On the other hand, a single point mutation within a critical gene may cause a devastating disease. There is also a third possibility though: new functionality may emerge as a result of a mutation.

Let’s consider the protein hemoglobin, for example, which binds oxygen and transports it throughout the body in the blood. Hemoglobin is made from two pairs each of two amino acid chains, called α and β (blue and red in the figure at right). The corresponding genes that code for α and β have similar sequences to each other, and are believed to have arisen when an ancestral globin gene (still present in marine worms, insects, and some fish) duplicated and slowly changed over time. While the ancestral form can bind oxygen just fine, the four chains of hemoglobin cooperate to do so even better.

Both the α and β genes have undergone further duplications followed by smaller mutations. As expected, many of the resulting genes have become irreparably damaged by mutations, but they continue to exist in the genome as inert DNA “fossils.” Others, however, remain active and now perform specialized functions. For instance, one set of β genes binds more tightly to oxygen than the others; it becomes active only during development to ensure that the fetus gets enough oxygen from the mother’s bloodstream. A few months after birth, fetal hemoglobin turns off and the adult form turns on.

To summarize, mutations come in many forms (e.g. rearrangements, insertions, deletions, duplications) and can lead to good, bad, or neutral effects within an individual. B cells depend on random mutations to produce novel antibodies. A few are productive, but the vast majority of B cells die unused. Yet the entire process works for our good! In the same way, mutations in germ cells can lead to no effect, disease, or new and better solutions, as we saw in the hemoglobin example. These are the ordinary (but masterful!) means by which God creates and sustains life.

Editor's Note: For more on the evolution of the immune system, read Randy's Isaac's post "Complex Specified Information Without an Intelligent Source" at the ASA website.