Behe’s B Cell Bravado, Part 2: Why Irreducible Complexity Fails
Intelligent Design proponent Michael Behe popularized the idea that some biological features are irreducibly complex. He defines an irreducibly complex system as one that is “composed of several well-matched, interacting parts that contribute to the basic function, wherein the removal of any one of the parts causes the system to effectively cease functioning” (Darwin’s Black Box, 39).
No problem there. Behe simply builds upon Aristotle, who wrote in his famous work Metaphysics, “The whole is more than the sum of its parts.” Every scientist accepts this principle.
Detecting design through irreducible complexity?
Behe goes further, claiming to have demonstrated that natural processes are insufficient to produce irreducible complexity:
The laws of nature can organize matter…If a biological structure can be explained in terms of those natural laws, then we cannot conclude that it was designed. Throughout this book, however, I have shown why many biochemical systems cannot be built up by natural selection working on mutations: no direct, gradual route exists to these irreducibly complex systems… (203).
If no gradual route exists, so the logic goes, then irreducibly complex systems must have been designed:
For discrete physical systems—If there is not a gradual route to their production—design is evident when a number of separate, interacting components are ordered in such a way as to accomplish a function beyond the interacting components (194).
Legions of scientists have rejected this argument. Why? Is it because they are godless atheists who deny the existence of an intelligent Creator? No. Some of Behe’s strongest critics are deeply committed Christians. These scientists simply see overwhelming evidence that irreducibly complex structures and systems have developed gradually through natural, evolutionary processes. For the believer, these processes are simply God’s chosen means of providentially ordering the world.
Darwin’s Black Box contains an entire chapter about the irreducible complexity of the immune system. Behe argues therein that the system for generating antibody diversity could not have developed by a gradual, stepwise process and therefore must have been designed. Here we examine some evidence to the contrary.
Recall from Part I that the antibody production system has three interdependent components, as shown in Figure 1: 1) clusters of gene segments that can be combined in different ways to code for antigen receptors (red and green), 2) start and stop signal sequences between these gene segments, called RSSs (orange and yellow), and 3) machinery to cut and rejoin the DNA at the RSSs (blue). ). (Also necessary are DNA repair proteins, which rejoin the severed DNA strands, but they are not specific to this process and are thus not included in the diagram.)
The RAG genes, which carry the instructions for how to make the RAG proteins, are critical for antibody gene recombination. Surprisingly, these genes are found in jawed vertebrates, but missing in jawless vertebrates and invertebrates. Thus, jawed vertebrates can make a vast array of antibodies, but the other 90% of species on the planet cannot. What could account for this seemingly arbitrary division? We have very good evidence that at least 450 million years ago, an ancestor for all jawed organisms acquired the RAG genes. Where might those genes have come from?
Transposons on the move
To answer that question, I need to first tell you about a strange and fascinating feature of bacterial DNA. Bacteria have short segments of DNA, called transposons, which can jump from one location to another in the genome (See Figure 2). By itself, DNA can’t do anything—it just provides the information the cell needs to make proteins. Proteins do all the mechanical work in the cell, including interpreting the instructions in DNA. Transposons jump around by carrying instructions like this:
The cell’s protein machinery reads the message and promptly makes the “scissors and glue” proteins. The scissors break the DNA at the “cut here” sequences (blue regions), and the glue pastes them back into the genome somewhere else. Where the transposon gets pasted is indeterminate—it may land within a gene, disrupting its protein-making instructions, or between genes, as shown in Figure 2.
A possible stepwise route to an irreducibly complex system
How does this relate to antibody gene recombination? Well, the RAG genes, which do the cutting to make functional antibody genes, are believed to have come from a transposon. The working model for how jawed vertebrates came to have antibody genes capable of recombination is known as the “transposon hypothesis.”
According to the hypothesis, a RAG-containing transposon invaded the genome of an early jawed vertebrate, probably through a bacterial infection. Such an infection would have occurred around 450 million years ago, shortly after the jawed and jawless vertebrate lineages diverged from their common ancestor.1
Suppose the transposon became inserted within a pre-existing, non-rearranging antibody gene (see Figure 3, step 1). (At this point in history, both vertebrates and invertebrates already had perfectly useful antibody-like receptor proteins—they just didn’t rearrange; see Part I.) The inserted transposon sequence would have the effect of splitting the gene into two segments.
When the cell began to read the host gene, the bacterial RAG genes were interpreted instead. The resulting RAG proteins snipped out the transposon and pasted it into a new location in the genome (step 2). Over time the RAG genes became immobilized in the genome, never to jump again. The RAG proteins still recognized the RSSs, though, and continued to excise the DNA between them. Now, instead of cutting out the transposon, they cut out the short stretch of DNA separating the two halves of the original antibody gene (step 3). Thus, the gene segments were reunited and voila! The antibody gene could make protein again.
Suppose that in a future generation, the gene segments duplicated. This would create more gene segments, allowing some limited recombination to take place. Suppose that later still, the whole set of gene segments underwent duplication. Successive rounds of duplication and divergence would lead to the diversity of gene segments we see today (step 4).
But is there any evidence it happened this way?
This sequence of events might sound like an evolutionary “just-so” story, but it actually rests on solid evidence. First, the RAG genes themselves bear striking resemblance to known bacterial transposons. Most immunologists think the similarity is too great to have occurred by coincidence. The RAG1 and RAG2 genes are also physically very close to each other in jawed vertebrates. This would be expected if they arrived together from an external source like a transposon. In addition, the signal sequences (RSSs) to which the RAG proteins bind are closely related to those found associated with bacterial transposons.
Perhaps most convincing: the RAG proteins can not only excise DNA, but insert one stretch of DNA into another in vitro (in a test tube). The RAG proteins don’t normally do this latter step in cells; there they are only used for DNA cleavage. In bacteria, transposon proteins do both, and in the test tube, the vertebrate RAGs can do both! How could the RAG proteins function just like those from a transposon, unless they had originally been part of one?
Irreducible complexity by a gradual route—God’s route
Behe argues that design can only be detected when no possible stepwise route to an irreducibly complex system exists. Here I have described such a route (and a well-supported one at that) by which the antibody diversity generating system—one of Behe’s best examples of irreducible complexity—could have developed gradually. We’ll examine his response to the data next time.
To me, the fact that the transposon hypothesis has passed though decades of scrutiny and experimental testing leads me not to question God’s design of the adaptive immune system, but to marvel at his ability to create it gradually through a long but ultimately fruitful process. Immunologist Ronald Plasterk reflected poignantly, “We may owe our existence to one transposition event that occurred 450 million years ago.” In my mind, while it may have occurred by entirely natural processes, the evolution of our immune system was no accident. The fact that we can use science to read this small story from God’s book of nature is a special gift indeed.
Applegate's series continues here.
1. Just a few years ago, scientists identified two closely-linked genes with high similarity to RAG in sea urchins. Sea urchins and their relatives (known as echinoderms) have long been recognized as the invertebrates most closely related to vertebrates. Sea urchins, being invertebrates, don’t make antibodies, and the RAG-like genes don’t seem to function in the immune response. If the transposon hypothesis is indeed correct, then either the RAG genes entered the sea urchin lineage on a separate occasion from the jawed vertebrates, or they entered even earlier than 450 million years ago via a common ancestor and were later lost in jawless vertebrates. In any case, whether or not the RAG genes were already present in the genome when the jawed and jawless vertebrate lineages split, it appears that they took on a new role only in jawed vertebrates—that of generating antibody diversity. The sequence and timing of events will likely be worked out as more invertebrate genomes are sequenced and the function of the sea urchin RAG genes is elucidated.
Behe, Michael J. Darwin’s Black Box. 1996.
Bottaro, Andrea, Inlay, Matt A., and Matzke, Nicholas J. “Immunology in the spotlight at the Dover 'Intelligent Design' trial.” Nature Immunology. 7(5), 433-435. May 2005.
Inlay, Matt. Evolving Immunity: A Response to Chapter 6 of Darwin's Black Box. http://www.talkdesign.org/faqs/Evolving_Immunity.html 2002..
Travis, John. “On the Origin of the Immune System.” Science. 324(5927), 580-582. May 2009.
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.