Genetics – Messier than you ever dreamed

kw: book reviews, nonfiction, biographies, short biographies, genetics, domains of life, trees of life, horizontal gene transfer

The Tangled Tree: A Radical New History of Life by David Quammen took me a week to read, and it was a week well spent. From the Acknowledgements section, it apparently took the author four years to research and write, and that was time well spent.

I have read articles and portions of books about the subjects of Tangled Tree, but I hadn't put it all together. One one level it is a biography of the work of Carl Woese. On another it is a record of the tremendous advances in our understanding the breadth of living things and our increasing understanding of just how complex evolutionary history and genetic inheritance really is. Certainly, there is a great deal more to learn.

Triggered by an offhand remark by Francis Crick, early in his career Carl Woese sought to create and to use tools to discern the sequences of chemical units in genetic polymers. He wanted to use genetic material to look deep into time, to find the relatedness of all life and its deep history. He settled on a group of RNA molecules that are strongly conserved and thus ubiquitous in all cells, the 16s RNA unit of the prokaryotic ribosome and the 18s RNA unit of the eukaryotic ribosome. They have the virtue, from this viewpoint, of changing very slowly, so deep relatedness between many organisms can be determined.

The first breakthrough came in 1977, when Woese produced a kind of RNA fingerprint for certain methane-producing microbes. His colleague Ralph Wolfe remembers him saying, "These things aren't even bacteria." Study of several other methanogens confirmed that impression. Then other special microbes were found that were also "not bacteria" and are now grouped with them in this new domain. After a few names were applied and rejected, the new domain of living things is now dubbed Archaea. They differ in several significant ways from Bacteria. Many thought Woese ought to get a Nobel Prize for this discovery. He thought so also; he was never one to even profess humility! Somehow, he didn't get one.

The book presents a tangled web of its own, discussing Woese's many collaborators and students, some of which became opponents, at least in his own mind. By 2000, when the first quasi-complete draft of the sequence of the human genome was presented, molecular biology had advanced so rapidly that Woese never fully understood what was going on, and was kind of left in the dust. The book gently presents his increasing paranoia as discovery after discovery was made by former students and colleagues. A core issue was the shape of the "tree of life".

The family tree of organisms has deep origins, and has been used in more ways than I thought were possible. Darwin included a sketchy tree in The Origin of Species. Trees became expressions of theory and political platforms within the biological community. But such trees got into trouble when certain further developments ensued. Two are key.

Firstly, beginning in 1967, ten years before Woese's discovery of the Archaea, Lynn Margulis (then Sagan) published her first paper about endosymbionts, as they are now called. In brief, these are the mitochondria (energy producing organelles) in all eukaryotic cells, and the chloroplasts (energy conversion—from light plus carbon dioxide to energy plus oxygen—organelles) in plant cells. It took Mrs. Margulis and her colleagues and sympathizers decades to make us all clear that these organelles started out as bacteria that took up residence in slightly larger cells, which then grew even larger, over the eons, and became more and more complex, to become all the Eukaryotes, or critters big enough to see without a microscope (and a great many that are still pretty tiny). You are a Eukaryote. Without a few thousand mitochondria in every cell in your body, you would die. Very fast. Or, rather, you could not exist at all.

A quick aside before going on. I used the work Prokaryote above. It refers to everything that is not a Eukaryote. In particular (so far!), it refers to Bacteria and Archaea, because they don't have a nucleus (the "Kary-" bit refers to the nucleus). Woese hated the term. But it is just too convenient a way to refer to the non-eukaryotic microbes that actually dominate all life on Earth.

Secondly, in the late 1990's, genome sequencing had produced enough data that researchers were able to determine that everywhere they looked (initially only among prokaryotic microbes), they saw DNA sequences that came from other organisms. Horizontal Gene Transfer (HGT) was soon understood to be very common among the Prokaryotes, including across the "domain boundary" between Bacteria and Archaea. Initially, HGT was studied as a mechanism by which pathogens quickly acquire, and share, antibiotic resistance. Now it is understood to be so widespread that some think there is really only one "bacterial species" with a couple of dozen semi-stable forms that we used to call species; and only one "archaean species", similarly. Or maybe they are all just one big mess of microbial soup! Stay tuned…

By the "mid oughts" (prior to 2010), it was becoming clear that Eukaryotes also contain substantial amounts of DNA that were acquired via various mechanisms of HGT. To date, it seems that 8% of human DNA is the complete genomes of hundreds or thousands of retroviruses. Viruses, particularly retroviruses, are one way that HGT operates in Eukaryotes.

There are shorter sequences that are still a puzzle, and many of them tend to be present in multiple copies. One sequence of middling size is apparently found three million times in the DNA of every cell in your body, and mine! Nobody yet knows why, or whether it does anything. If it does do something, it must do a lot of it! Nobody yet knows where they come from, except from "some other critter". The result is a "tree" of life that resembles a web, a network, anything but a tree. It is hard to even use the term "tree of life" in any meaningful way any more.

A typical human body contains about 37 trillion eukaryotic cells, of a few hundred varieties that make up the tissues of the body. That same body is inhabited, without and particularly within, by more than 100 trillion prokaryotic cells, of several thousand "species" of Bacteria and Archaea. They are not just passive. Certain ones enable you to eat certain foods. The prokaryotic "glove" of organisms on our skin actually prevent many pathogens from attaching and attacking us. A similar "glove" lines our digestive tract. There is so much still to learn about all this! One consequence is this: our cells and their nuclei (where the DNA is) are pretty robust, and keep inside and outside separate. But disease and various insults to our body's integrity can allow DNA from outside some of our cells to get inside, and sometimes to be incorporated. That is another variety of HGT.

Carl Woese didn't like his work being eclipsed. He had the misfortune of making a great discovery that was soon just one of many astonishing discoveries, and he sort of got nudged aside. Though he was awarded many prizes and much praised, without a Nobel Prize, it seems he could never be satisfied. Yet he is remembered as a core figure in the great revelations about the way genetics works, that dominated biology in the late 20^th and early 21^st Centuries.