Daniel Nebert
Cincinnati, Ohio, United States
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This year we celebrate the 156th anniversary of Charles Darwin’s book, On the origin of species by means of natural selection, one of the greatest landmark scientific advances of all time. As the ship’s only “naturalist biologist”, Darwin sailed around the world from England (1831–36) on the HMS Beagle. His observations and many collected samples, made while visiting the Galapagos Islands for only five weeks, set into motion the “theory of natural selection.” Although he had conceived the broad idea before 1840, the first edition of his book was not published until 1859, largely because of his religious background: in 1831 he had received a BA degree in theology from Cambridge University, and his wife was a devout Anglican. Darwin’s developing realization–that all life on the planet originated from a common ancestor and continues to evolve based on “survival of the fittest”–flew in the face of religious thought at that time.
After Darwin published the Origin of Species in 1859, the patterns of social thinking were re-formed around the concepts of evolutionary biology. Within a little more than a decade, the concept of evolution was adapted to almost every field of social and philosophical enquiry. By contrast, previous philosophical and scientific investigations had looked on any concept or subject that was fixed and permanent, as superior to anything that would change or pass away. Interestingly, Darwin’s grandfather Erasmus Darwin had written in 1794 a philosophical essay, Zoonomia, in which he had suggested that all warm-blooded animals may have arisen from “one living filament.”
Darwin later published The Descent of Man, devoted to the workings of natural selection among civilized nations. He saw man as a social animal who from earliest times had practiced division of labor and exchange of goods. He felt that the struggle among races depended entirely on intellectual and moral qualities, rather than physical qualities.
What was it about the Galapagos Islands that stimulated Darwin? Rising above the ocean surface three to four million years ago, each volcanic island developed its own “mini-climate,” and the archipelago was sufficiently distant from the Ecuadorian coast that relatively few animals and plants arrived from the mainland. Consequently, each species that had arrived diverged over time, adapting to its changing environment. For example, Darwin observed that finches on different islands had developed variations in beak size and shape–related to the type of seeds available for food.
These observations can now be explained on the basis of irrefutable scientific facts–as a result of new archeological data and radioisotope-dating of rocks and the fossils therein, combined with the discovery of the DNA helix (1953), techniques to sequence DNA in the 1970s, forty years of advances in molecular biology and genetics, and during the past two decades development of high-throughput genomic DNA-sequencing and powerful bio-informatics software programs. We now know that DNA is the principal genetic material, existing as long chains comprising almost always the same four bases (adenine, guanine, thymine, cytosine) that exist in chromosomes of a cell. Genes are made of DNA, located in linear fashion along each chromosome; they code for proteins, which represent long strings of amino acids. Variations of specific bacterial genes often also exist in yeast, fly, worm, fish, mouse, and also humans; however, mutations in DNA, and thus changes in amino-acid sequence of each protein, have slowly occurred–over millions of years.
If a specific protein is 80% similar between human and mouse, 70% between human and opossum, and 56% between human and fish–then there are mathematical formulae to estimate how long ago that divergence occurred between: human and mouse ~70 million years ago (MYA); human and opossum ~175 MYA; and human and fish ~420 MYA. We also know animals that have been living apart from one another for more than a million years can no longer interbreed and thus are designated as two separate species.
What follows are a dozen examples–among many hundreds that can now be cited–of biological discoveries that support Darwin’s ideas. In every case, the overwhelming reason for an evolving improvement of a species was better survival: finding food, avoiding predators, and reproducing.
Snake legs
Animals having two front legs and two hind legs exhibit regions along their vertebrae that give rise to fore-limbs and hind-limbs. We now know that almost all the same genes (from frogs and salamanders to humans) are used in both arm and leg formation. So, why do snakes have no limbs? Actually, the python’s skeleton contains hundreds of similar vertebrae; rudiments of fore-limbs are absent, but there are vestigial hind-limbs. The expression of one gene is known to stimulate formation of hind-limb buds, while expression of a second gene in snakes prevents activation of hind-limb growth. By blocking this inhibition (that prevents activation of hind-limb growth), scientists in England were able to rescue this pathway—leading to pythons having more than two hundred pairs of hind-legs! Early in the evolution of snakes, therefore, this inhibitory pathway allowed snakes to preferentially evolve without legs. For what reason? Obviously to move more stealthily and become more successful at catching prey or avoiding predators.
Evolution of the eye
It’s now obvious that “sensing light” is extremely important for living things to find food, avoid predators, and reproduce. Even one-celled organisms often have “eyespots,” containing photoreceptor proteins capable of sensing light. Over more than 3.5 billion years of time, eyespots are known to have evolved independently–somewhere between 40 and 65 times! There appear to be two fundamental “designs,” suggesting that two patterns emerged in different locations on the planet, both sufficiently successful to have become fixed and been passed on independently to future generations. One design is carried by protostomes (mollusks, segmented worms, insects, spiders), the other by deuterostomes (starfish, sea squirt, sea urchin, and all animals having a spine including humans). Protostomes have only opsins (light-sensing proteins). In the other lineage, the basic light-processing unit is the photoreceptor cell, consisting of two different types of molecules: opsins, surrounded by chromophores (pigmented cells that distinguish colors). Jellyfish have twenty-four pairs of eyes, one pair of which resembles the rods and cones of the human eye! Sponge larvae are very simple animals without nerve cells, yet even they can detect light.
Why would eyes evolve repeatedly over time? The selective pressure to sense light versus darkness must obviously be extremely strong: the better an organism can “see”, the better that species can survive (find food, avoid predators, locate mates for reproduction).
Antifreeze protein
For decades, scientists have known that fish at the north and south poles are resistant to freezing because of “antifreeze” proteins. Now we know that the Antarctic fish antifreeze protein arose from a pancreas-derived gene encoding a protein within which there are forty-one repeats of several amino acids; this gene was estimated by DNA sequencing studies to have arisen between 10 and 14 million years ago–which correlates well with the estimated archeological date when the Antarctic Ocean froze over.
By contrast, the Arctic fish antifreeze protein is derived from a totally different gene and originated about 2.5 million years ago–most likely because of the Arctic Ocean glaciation at that time (which was later than the south pole). Here we have two different fish species, at the two extremes of the earth, needing a protein (at different planetary times) in response to their environment which suddenly became much colder! Again: these antifreeze genes evolved for reasons of survival.
Whales and dolphins
Whales and dolphins have lived in water for millions of years but, like us, as mammals, they breathe air; and they give birth to and suckle live young. Mammals originally evolved on land. From studying fossils (teeth, but especially bones of the inner ear and limbs), we know there was a series of animals, through time, changing from “land-animal” features to “water-animal” features; one such now-extinct creature–called a raoellid (which would have looked like a very small dog) was closely related to “even-toed ungulates” (modern-day cows, sheep, deer, pigs, and hippos). Recent studies comparing DNA sequences (in genes regulating teeth and bone development between human and whales or dolphins) are consistent with the fossil data.
Evolution of feathers
Archaeopteryx, a dinosaur with feathers, had been the earliest known bird. Why should feathers have evolved? No doubt feathers decreased air resistance while sailing from one tree to another, which became an efficient means of attacking small prey or eluding predators. Recent fossil evidence has now identified Anchiornis, Xiaotingia, and Aurornis also as dinosaur species having feathers and, indeed, having laid eggs in nests similar to modern-day birds. Geological findings (huge crater in Gulf of Mexico off the Yucatan Peninsula) support the idea that large land-dinosaurs became extinct about 66 million years ago because of a meteorite striking the earth and causing sudden and extreme planetary cooling. Small, feathered dinosaurs undoubtedly survived and gave rise–more recently than 66 million years ago–to today’s birds. In fact, by the type of variation in the number of wing feathers and DNA analysis, velociraptor (“raptor” for short) has been shown, among all dinosaurs, to be most closely related to the modern-day turkey.
Mutual benefit: co-evolution
“Co-evolution” is the evolving of two species that depend on one another. Recent studies have shown a particular type of ant that eats a special fungus. The ant benefits by eating the fungus; the fungus benefits by ant excretions for its food. Genes associated with these pathways, in both ant and fungus, have evolved together–over at least 80,000 years–to ensure greater success (in diet and reproduction) for both species.
Another co-evolution example concerns the black swallowtail butterfly. After mating, this insect lays its eggs on plants of the carrot family (e.g. parsley, dill, and fennel) where the developing pupa expresses a unique enzyme (CYP6A) that breaks down otherwise noxious chemicals in these plants, and then uses these plants for food. Almost all other insects avoid plants of the carrot family because they do not have that particular form of CYP6A. Both species benefit: the insect feeds on the plant, and the plant gets pollinated by the insect.
The human spine
The vertebrate spine of nonhuman mammals is best designed for walking on all fours. However, during the past five million years, early human-like hominids began walking upright, as an adaptation (avoiding predators, catching animals, and finding mates for reproduction). Today, by age seventy almost every human being has some degree of arthritic degeneration of the lower spine–because our spines are not properly suited to walking upright. Similar problems with shoulder, hip, knee, and ankle joints are also associated with our ancestors millions of years ago–changing from walking on all fours and climbing trees to walking upright on land. Genes (DNA sequences) involved with embryonic development of these joints are consistent with the fossil data.
Visual stress
Guppies were raised in a tank where they could see (behind thick glass) predator fish. As the guppies continued to breed in the presence of this severe visual stress, their coat color gradually changed, so that they looked “less like guppy prey.” This complete change in guppy coat color took only nine generations to accomplish; this is another example of “adaptive evolution.”
Pesticide resistance
Tobacco budworms in a cotton field, when treated with a pesticide, slowly become resistant to that chemical. These resistant animals were then grown in a Texas lab in the absence of pesticide; after forty-five generations, it was found that–once again–these budworms had become sensitive to that pesticide. These animals could then be placed in the same cotton field and, over time, slowly became resistant once again to that pesticide. Changes in the genes involved in detoxication of that pesticide are consistent with this progression from sensitivity to resistance to sensitivity.
Antibiotic resistance
Bacteria usually double in number every thirty minutes–meaning that one week will give rise to 336 generations of bacteria; this would be about the same as 8,400 years for humans. Most of us have heard of bacteria “becoming resistant” to a particular antibiotic; this is because of mutations in DNA that occur over many generations. Numerous mutations “just happen”, but a beneficial change (to the bacterium, such as resistance to streptomycin while in the presence of that antibiotic) is more likely to be successfully passed on to future generations. Methicillin-resistant Staphylococcus aureus (MRSA) is a modern-day example of evolution that is occurring in hospital patients; although clinically undesirable, this mutation is beneficial to the bacteria. Multi-drug resistant tuberculosis is another recent clinical problem as the result of bacterial evolution.
Chemotherapy resistance
Many cancers likewise give rise to cells that become resistant to chemotherapy. At first, most cells are “killed off” by the anti-cancer agent; some months later, a chemotherapeutic-resistant form of that tumor can develop. Antibiotic-resistance and chemotherapeutic drug-resistance are both examples of “adaptive evolution.”
Conclusion
Today Charles Darwin would be very pleased to see that evolution is alive and well! Cutting-edge genetics and comparative genomics–along with complementary studies in archeology and radiocarbon-dating–continuously build a stronger science to support his ideas. For the past century the topic of “evolution” has remained highly controversial in certain regions of the US, although most living outside the US do not see evolution as a problem. Some Americans say that “one must believe either in evolution or in a divine creation”, implying these two concepts are unrelated and opposite. This notion, however, could not be further from the truth. It is hard for many of us to comprehend how many generations of each species–and therefore opportunities for mutations–occur over billions of years of time. Beyond the scope of this article is “epigenetics” (changes in gene expression that are independent of mutations), which is another chromosomal phenomenon that can advance evolution.
The definition of Life is the insertion of “Order” into our expanding chaotic universe of “Disorder.” One can see Order (increased free energy, decreased entropy) in the formation of a crystal, function of a virus, folding of a protein, or the process by which DNA produces a particular protein that can adapt to environmental changes in order for the organism to better survive. Belief in God (Order, as opposed to Chaos; Good, as opposed to Evil; Love, as opposed to Hate), and our current understanding and acceptance of evolution, are therefore viewed by many of us scientists as mutually compatible.
DANIEL W. NEBERT, BA, MS, MD, completed pediatrics training at UCLA Medical Center and then postdoctoral fellowship in the National Cancer Institute (Bethesda, MD). For the past four decades, he has carried out basic science and clinical research in genetics at the National Institute of Child Health & Human Development, and then as professor at University Cincinnati Medical Center and Cincinnati Children’s Hospital (Ohio). His primary research theme has always been: “Given the same dose of a drug (e.g. phenytoin, valproic acid), or same exposure to an environmental agent (e.g. cigarette smoke, cadmium), why do any two individuals respond differently?” He is the author of more than 640 publications in the scientific literature and has written many dozens of invited “Opinion” articles for The Cincinnati Enquirer and Oregonian newspapers.
Highlighted in Frontispiece Winter 2015 – Volume 7, Issue 1
Winter 2015 | Sections | Science
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