Molecular Phylogenetics: A New Way to Tell the Story of Evolution

The new science of molecular phylogenetics tells the story of evolution with no need to consult the fossil record. It has produced some surprises, including a whole new domain of life, the archaea.

Darwin’s 1859 book On the Origin of Species was a well-written, well-argued introduction to evolution, to the theory that populations evolve and species differentiate through a process of genetic variation, competition for resources, and adaptation through natural selection. It was a tour-de-force supported by a mass of evidence from his observations. But it was far from perfect. Darwin was handicapped by incomplete knowledge. He had no understanding of the laws governing inheritance. Genes, chromosomes, and DNA were unknown. There was no good way to define a species.

Modern science has given us a better, more objective way to tell the story of evolution: molecular phylogenetics. The fossil record is no longer necessary. We can read the deep history of life from the sequence of nucleotide bases and amino acids in certain long molecules: RNA, DNA, and a few select proteins. We thought there were two domains of life, bacteria (prokaryotic organisms that lacked a nucleus) and eukaryotes that had a cell nucleus and constituted all other living organisms, both plants and animals. Molecular phylogenetics has provided us with three big surprises that have fundamentally changed how we think about what we are, who we are, and how life evolved on our planet:

  1. A whole new domain of life known as the archaea.
  2. A whole new mode of hereditary change, horizontal gene transfer.
  3. The strong likelihood that humans probably evolved from creatures that, as recently as 40 years ago, were not known to exist.

Science writer David Quammen tells the story in his new book, The Tangled Tree: A Radical New History of Life.

The players

Quammen brings the story to life through the personalities of the players, showing how each discovery was made, how it was rejected by other scientists, and how it was finally accepted. Francis Crick was the first to suggest, in 1957, that comparing slightly different versions of the same protein in different species could allow inferences about the degree of relatedness between the species; he called it protein taxonomy. In 1963, Zuckerkandl and Pauling suggested using molecular differences as a kind of molecular clock to tell us how much time has passed since lineages split, what the ancestral molecules must have looked like, and what were the lines of descent.

Carl Woese, described by Quammen as a “brilliant crank,” used an elaborate, time-consuming, dangerous process of electrophoresis to study fingerprints of the genetic sequence of ribosomal RNA molecules from different organisms. He learned to immediately recognize fragments that were characteristic of all prokaryote bacteria. In the ribosomal RNA of methanogens, he got weird results that were neither prokaryote nor eukaryote. He commented to a colleague, “these things aren’t even bacteria.” He realized that methanogens must be classified in a hitherto unknown third domain of life, which eventually became known as the archaea. Woese’s breakthrough came in 1977. The scientific world was shocked. Carl Woese was doubted, dismissed, and ridiculed. Acceptance was slow but inevitable as more evidence accumulated.

Another important player was Lynn Margulis, the first wife of Carl Sagan. In 1967 she proposed the idea that living ghosts of other life forms exist and perform functions inside our very own cells. Whole organisms have become engulfed by the cells of other organisms through the process of endosymbiosis. The mitochondria in our cells and the chloroplasts in plant cells are descendants of captured organisms. Margulis was right about this, but wrong about much else. Among other things, she became an AIDS denialist, called 9/11 a false flag operation, and embraced the questionable diagnosis of chronic Lyme disease.

And then there was Barbara McClintock, the visionary corn geneticist who was first to detect transposable elements that jumped from one chromosome to another. In addition to these major players, Quammen tells the stories of many other fascinating characters.

The tree of life?

The traditional idea of a tree of life is no longer valid. Rather than arising from a single trunk, life may have begun as a mound of precellular life, a “common ancestral state”. Genes can be transferred horizontally; they can jump from branch to branch and from organism to organism as well as descend in a vertical, treelike pattern.

A resurrected Shigella serotype from a patient who died in 1915 was resistant to several antibiotics that were unknown at the time. It seems that antibiotics exist in the wild, and bacteria develop resistance to defend themselves in the struggle against other bacteria. Resistant genes can be passed horizontally to other bacteria: this not only contributes to the problem of antibiotic resistance but helps explain bacterial evolution in general. Bacterial evolution is web-like, not tree-like. Bacterial boundaries are blurry. Bdelloid rotifers are strange creatures that have gone without sex for 25 million years. No one has ever seen a male bdelloid rotifer. Yet they are a great success. They have diversified without sex into more than 450 species because they have a strong propensity for horizontal gene transfer.

Bacterial genes have been found lurking in normal human genomes, and they are 210 times more common in tumor cells than in healthy cells. Are they a cause of cancer?


Early in evolution, whole bacteria were engulfed by eukaryotic cells to become mitochondria and chloroplasts. Before capture, they had been recipients of horizontal gene transfer from other kinds of bacteria. Parts of genomes had existed within other genomes before becoming parts of still other genomes, including yours. Quammen compares it to a snarl, a mess, a plate of spaghetti, but clearly not a tree.

Darwin was not wrong

Headlines blared, “Darwin was wrong!” This provided a convenient weapon for creationists and neo-Darwinists and gave comfort to the enemies of science. No, Darwin was not wrong. The new information went beyond Darwin’s thinking without negating that thinking, just as Einstein and quantum mechanics went beyond Newton’s thinking without negating it.

Junk DNA that isn’t junk

We carry a lot of DNA that doesn’t code for genes. Half of the total genome is in the form of relatively short bursts of code that repeat themselves and can not only copy themselves but can jump around to different parts of the genome. Once called “junk DNA”, they are now called “transposable elements” or “transposons” and are far from useless. They can control gene expression and are clues to a rich paleontological trove of information about human evolution. Plus, they add raw genetic material that increases the chance of new genes taking shape, genes that might mean the difference between survival and oblivion if the environment changes.

The origin of eukaryotes remains a mystery

If there are three domains of life, the two prokaryotic domains of bacteria and archaea that lack a cell nucleus, and a third domain of eukaryotes with nuclei, what happened to set the eukaryotes on the path that led to bigness and complexity, to develop into all animals, all plants, all fungi, and all microbes with nuclei? We don’t even know if the Great Mitochondria Capture was a cause or effect. It’s still possible that the eukaryotes developed within the archaea. Some scientists argue that we should go back to a 2-kingdom system, that we are direct descendants of archaea, a form of life unimagined before 1977.

Three errors and a conclusion

This upheaval in thinking has provided three counterintuitive insights that challenge the categorical thinking about aspects of life on earth: species, individual, and tree. Species and individuals can no longer be considered discrete identities, and inheritance doesn’t always flow vertically like a tree.

We are having to re-evaluate what it means to be a human. We are not a unique, separate species. We have been colonized by other organisms; our genomes are one-twelfth virus and also contain bacterial genes; we harbor huge microbiomes with more organisms than we have cells of our own. We are commensal, symbiotic, ecological communities. We contain Neanderthal and chimpanzee genes. We are not alone. As the poet Walt Whitman said, “I contain multitudes.”

This article was originally published in the Science-Based Medicine Blog

Dr. Hall is a contributing editor to both Skeptic magazine and the Skeptical Inquirer. She is a weekly contributor to the Science-Based Medicine Blog and is one of its editors. She has also contributed to Quackwatch and to a number of other respected journals and publications. She is the author of Women Aren’t Supposed to Fly: The Memoirs of a Female Flight Surgeon and co-author of the textbook, Consumer Health: A Guide to Intelligent Decisions.

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