Evolution of the Immune System

Carl Zimmer has another stellar post on his blog, this one about the evolution of the immune system. It's a review of this article (PDF format) by Klein and Nikolaidis, entitled The descent of the antibody-based immune system by gradual evolution. This article points up a very important point that I was making in an exchange in the comments a few weeks ago, about nested heirarchies as a powerful line of evidence for evolution. All animals, living or dead, can be placed into groups based upon shared derived characteristics and those groups form tree-like heirarchies. Branch B splits off from Branch A and numerous branches then come off from B, but they all share a specific trait, then one of those branches splits off and all of the animals on the new Branch C have the same shared traits as those on Branch B, but also additional traits unique to C, and so forth. Evolution explains these heirarchies quite easily through common ancestry - all of the animals on B have a common ancestor (the first B species, from which all of the other B species split off) and all of the animals on C have two common ancestors (the one that split off to form B and the one that split off to form C), and so forth. Zimmer demonstrates this by looking at a small example and a large one. First, the small one - whales:

All living species of whales look a lot like each other, and not very much like any other animals. They all have horizontal tail flukes, blowholes, and smooth skin free of scales or fur. Darwin argued that whales were not simply created in the oceans in their current form, but instead descended from land mammals which had adapted to life in the ocean. He pointed out that whales share a number of traits with land mammals, such as milk and a placenta. Their blowhole connects to a set of lungs very much like those of land mammals and nothing like the gills of fish.

Darwin wigged out more than a few people with this argument. Whales just seemed too different, too distinct to have evolved by small steps from a four-legged ancestor. And creationists loved to point out how unlikely this transition seemed--on par with turning a cow into a shark. They also liked to point out that no intermediate fossils had ever been found. But as I wrote in my book At the Water's Edge, paleontologists began to find those fossils in the 1980s. Today, the transition whales made from land to sea is wonderfully well documented. Paleontologists have found complete skeletons of creatures such as the 45 million year old Ambulocetus (reconstructed here by the gifted artist Carl Buell). The transformation was not some sudden macromutation, but a gradual series of changes over millions of years, featuring shrinking legs, lengthening tails, loosening hips, and migrating noses.

The Carl Buell mentioned there, by the way, is a gentleman who often leaves comments here under the nickname OGeorge (short for Olduvai George, which for some reason just cracks me up). At any rate, what Zimmer points out here is important. All whales share a given set of traits, and you can see those traits slowly develop in the series of fossils that have been found over the last couple decades. You can see a wonderful and detailed examination of that fossil evidence in Zimmer's book, At the Water's Edge, which is really one of the best written popular books on evolution available. Next, Zimmer moves to the immune system:

Our immune system is as awesome as a whale's body--in terms of the complexity of its parts and the way those parts work together so well. It keeps viruses, bacteria, tapeworms, and even cancer cells at bay, while generally sparing our own tissues from its withering attack. All animals share a rudimentary immune system, but Klein and Nikolaidis focused on a second system that is found only in vertebrates. Only we vertebrates have immune systems that can learn.

This learning system is a network of cells, signals, and poisons. Among its most important cells are T cells and B cells. They originate in the bone marrow, although the T cells have to finish their development in the thymus, an organ near the heart. These cells are unusual in many ways, most important of which are some of the receptors they make on their surface. The cells have a special set of tools that cut up the receptor genes and paste them into new arrangements, so that the genes produce receptors with new shapes. Depending on its shape, a receptor can grab onto certain molecules. Those molecules may come from a bacteria toxin, or they coat nerves or muscle cells...

You can find this same remarkable system in humans, albatrosses, rattlesnakes, bullfrogs, and all other land vertebrates. You can also find it in most fish, from salmon to hammerhead sharks to sea horses. There are some variations from species to species, but they've all got B cells, T cells, antibodies, thymuses, and the other essential components. But you won't find it in beetles, earthworms, dragonflies, or any other invertebrate on land. Nor will you find it in starfish, squid, lobsters, or lampreys in the water. All these other animals rely instead on rudimentary immune systems that cannot learn.

For those who reject evolution, this sort of pattern tells them nothing. Like everything else in nature, they can only wave their hands and declare it the inscrutable work of a designer (lower case d or upper case D as they are so inclined on a given day). But immunologists and other scientists who actually want to learn something about the immune system find this view useless. Instead, they look at how animals with an antibody-based immune system are related to one another. And what they find is both straightforward and astonishing. All of the living animals with an antibody-based immune system descend from a common ancestor, and none of the descendants of that common ancestor lack it. That means that the antibody-based immune system evolved once, about 470 million years ago.

I need to back up in the history of life a few hundred million years to explain how scientists know this. Studies on fossils and genes agree that everything we call an animal (including sponges and jellyfish) shares a common ancestor not shared by plants, fungi, or other major groups of organisms. Exactly when that ancestor lived is a subject of fierce debate, but one of the latest estimates puts the date at about 650 million years ago. This ancestor probably had a simple immune system, because all animals, from sponges on, have at least some sort of defense against pathogens. Over the next 100 million years or so, the major groups of animals branched off from one another, and while some branches evolved some new defenses of their own, the antibody-based immune system only appears in our own branch, the vertebrates.

Animals with some--but not all--of the key traits of vertebrates, such as heads and brains, lived at least 530 million years ago. The only living relics of these early branches are hagfish. Later, our ancestors also evolved a vertebral column, becoming true vertebrates. Lampreys represent the deepest branch of vertebrate evolution, splitting off perhaps 500 million years ago from their common ancestor with us. They lack many traits that other vertebrates have--most obviously a jaw. A number of other weird jawless vertebrates filled the oceans between about 500 and 360 million years ago, but except for lampreys, they're all long gone. One of these branches gave rise over 470 million years ago to fish with jaws--known as gnathostomes. Gnathostomes later gave rise to sharks and other "cartilaginous" fishes, as well as ray-finned fishes, and land vertebrates.

You may have already guessed the kicker of all this history. Lampreys and invertebrates don't have an antibody-based immune system. Sharks, ray-finned fish, and land vertebrates do. Sharks, ray-finned fishes, and land vertebrates all share a common ancestor that is not shared by lampreys or other invertebrates. The simplest way to explain this coincidence is to conclude that the antibody-based immune system evolved after lampreys branched off from our own lineage, but before sharks and other living gnathostomes began to branch apart. We can't dig up fossil antibodies, but we can know when they evolved.

He then goes on to detail the components of the more primitive immune system found in lampreys and show how those components could have been altered through mutation and selection to form the new system in the common ancestor that all vertebrates share, the system that we evolved with. Through the usual processes of gene duplication and mutations that may change the timing of certain genes, the primitive system could have been converted to the immunity-based system through a fairly simple series of adaptations:

Scientists have sometimes treated the transition from rudimentary immune system to antibody-based immune system as a great leap. Lampreys don't have antibodies, B cells, T cells, thymuses, or the rest, and all gnathostomes do. Some creationists have even tried to turn this into an argument against evolution, claiming that something as complex as the adaptive immune system could not have emerged gradually. But it's important to bear in mind that tens of millions of years of evolution separate our common ancestor with lampreys and the earliest gnathostomes. And in their new paper, Klein and Nikolaidis argue that the evolution of the antibody-based immune system was a lot like the evolution of whales: a gradual, step-wise process.

Most of the components of the antibody-based immune system were actually already in place long before gnathostomes evolved. Lampreys, for example, don't have a thymus, but they do have the structures and cell types that form the thymus. In gnathostomes, the thymus develops as cells switch on special genes in a particular order. Lampreys have these genes, as so many other animals. Instead of building thymuses, they build other structures, such as eyes and gill arches. It would have only required altering the switches that determine when and where these genes become active to produce a new organ.

B cells and T cells are known as lymphocytes. Lampreys don't have lymphocytes, but Klein and Nikolaidis point out that they do have "lymphocyte-like cells." (The picture above shows what these cells look like.) Lymphocyte-like cells develop like lymphocytes, under the control of many of the same genes that control the development of lymphocytes. Once they are mature, these cells have almost the same structure and chemistry as lymphocytes--but they don't produce the antibodies and receptors of B cells and T cells. Exactly what they do in lampreys isn't clear.

What about those receptors and antibodies? Klein and Nikolaidis point out that they aren't quite as novel as they may look at first. They are made up of building-blocks of simple proteins arranged in different ways. And guess what--many of these simpler proteins are found in lampreys and invertebrates, where they serve other functions. The same goes for many of the proteins that B cells and T cells use to communicate with one another. Other proteins are made by genes that are unique to gnathostomes, but show a kinship to entire families of genes found in other animals. The most likely explanation is that an ancestral gene duplicated by accident, and later one of the copies was recruited to the evolving immune system.

It should also be noted here that none of this is at all farfetched. Molecular biologists have seen all of these processes at work in the laboratory, in particular the adaptation of duplicated genes. It is common to see a genome undergo such a duplication so that two of the same type of protein are produced instead of one. The first protein continues with its normal function, and the extra protein, through successive generations, is adapted to a new function. Indeed, this is one of the most obvious answers to the classic "how does mutation lead to an increase in information in the genome" question, as Ed Max points out:

The gene for a primordial oxygen-carrying protein is thought to have duplicated leading to separate genes encoding myoglobin (the oxygen-carrying protein of muscle) and hemoglobin (the oxygen-carrying protein of red blood cells). Then the hemoglobin gene duplicated, and the copies differentiated into the forms known as alpha and beta. Later, both the alpha and beta hemoglobin genes duplicated several times producing a cluster of hemoglobin-alpha-related sequences and a cluster of hemoglobin-beta-related sequences. The clusters include functional genes that are slightly different, that are expressed at different times during the development of the embryo to the adult, and that encode proteins specifically adapted to those developmental periods. Other examples of gene families that appear to have developed by such duplication and differentiation include the immunoglobulin superfamily (comprising a large variety of cell surface proteins), the family of seven-membrane-spanning domain proteins (including receptors for light, odors, chemokines and neurotransmitters), the G-protein family (some members of which transduce the signals of the seven-membrane-spanning domain family proteins), the serine protease family (digestive and blood coagulation proteins) and the homeobox family (proteins critical in development). A large part of the increase in information in our genomes compared with those of "lower" organisms apparently results from such gene duplication followed by independent evolution and differentiation of duplicated copies into multiple genes with distinct function.

We've also observed how frame-shift mutations can produce an entirely new trait, for instance in the bacteria that can digest nylon. So none of this is purely theoretical. We've seen the same process at work in the lab and in the wild, so we know that it happens. At that point, it's simply a matter of applying known processes to explain how a trait developed in the past. By comparing the systems of those animals that share a given trait with the oldest living animals that do not share it, we can observe what type of system preceeded the one we're attempting to explain and see the steps necessary to get from A to B. And with the astonishingly rapid advance of total genomic sequencing, today's molecular biologists are also quite often able to pinpoint the precise mutation or series of mutations that did take place in order to build the new trait.

This is exciting research. It's the type of research that can only be made possible by having an explanatory model from which one can derive hypotheses and then test those hypotheses. Contrast that with ID, which is an exclusively negative argument relying solely upon the alleged inadequacy of evolution to explain specific systems (not evolution, therefore God) and you see why ID advocates are unable to point to any specific research for ID as opposed to research against evolution: there simply isn't any, nor could there possibly be without the development of a genuine theory with explanatory power.