Uprooting the Tree of Life

Image: Ned Shaw The cell--the irreducible unit of life on Earth--has an estimated history nigh on 3.5 billion years. Scientists since Charles Darwin have attempted to trace that history to a so-called last common ancestor. Comparative physiology and fossil records can take one only so far, so many researchers are trying to reach the tree of life's roots with tools of a genetic nature. Yet, the more they dig, the more convoluted those roots appear to be. Lateral gene transfer, the square peg in

Sep 16, 2002
Brendan Maher
Image: Ned Shaw

The cell--the irreducible unit of life on Earth--has an estimated history nigh on 3.5 billion years. Scientists since Charles Darwin have attempted to trace that history to a so-called last common ancestor. Comparative physiology and fossil records can take one only so far, so many researchers are trying to reach the tree of life's roots with tools of a genetic nature. Yet, the more they dig, the more convoluted those roots appear to be. Lateral gene transfer, the square peg in cellular evolution's round hole, casts doubt on the verity of the Darwinian tree with its single point of origin and straight branching. This uprooting leaves room for numerous speculations about life's origins.

These theories are esoteric, often involving hypothetical organisms. The discussions are heated, with epithets such as "sheep" and "crafty buggers" thrown about. The language is at times colorful, even unprintable. "He could be dead ... wrong," says one evolutionary biologist about another, namely, Carl Woese.

Put 10 theorists in a room, and 12 differing opinions will likely emerge. With ideas ranging from an endosymbiotic origin for eukaryotes to a tree depicting such complex cells as the most ancient, the kingpin of much of this discussion is Woese, who, for the past 30-plus years, has stirred the primordial pot to bring forth evocative concepts, challenging Darwin's single-trunk tree of life and making friends and enemies along the way. Woese's latest paper, which suggests that the three types of cells could actually have evolved from a larger pool of prehistoric organisms, does not disappoint.1

PAST AND PRESENT Molecular biology and evolution have combined to support many phylogenetic trees. Woese, a microbiology professor at the University of Illinois, helped consummate this often times rocky marriage in the 1960s. Before then, he says, "Molecular biology thought of evolution merely as an historical accident not worthy of consideration. Compare that to the 19th century when Darwin was the message of the day." Woese traced sequence differences in microorganisms for the molecules he believed to be most central and conserved in life--the ribosomal RNAs responsible for protein translation, the universal language of cells. In so doing, Woese made a textbook-changing discovery, convincing most that archaea exist as a domain of life distinct from bacteria and eukaryotes. From this, Woese constructed the first phylogenetic tree of microorganisms, leaving bacteria at the root, with archaea and eukaryotes branching off at a later date.

Photo: Courtesy of Eugene V. Koonin
 Eugene V. Koonin

The model spurred interest and research. When The Institute for Genomic Research in Rockville, Md., uncovered large sections of archaeal gene sequences within the genome of Thermatoga maritima, a heat-loving bacterium near the base of Woese's tree, the single-gene history method was severely shaken.2 Suddenly, researchers realized that one gene could give one history, while another might paint an entirely different portrait. "Horizontal gene transfer just uproots the tree of life," says Eugene V. Koonin, senior investigator, National Center for Biotechnology Information. Gene transfer has affected nearly every gene family, Koonin says, but he finds that single-gene phylogenetic construction is useful--to a point. "It will tell you the story of a gene family--the story of a gene for short--but it will not necessarily tell you the story of the organism."

Woese says he believes that with few exceptions, organismal history can be traced to a certain point. In his latest paper, he posits this point as a root or last common ancestor that must be considered in a wholly different light.1 Challenging Darwin's theory of common descent, he states that the three cell types emerged not from one, but from many cell types--imagine a tree with three trunks and an interacting root network. The cell types, he theorizes, evolved from a community of cooperative entities freely exchanging genes at unimaginably high rates until particular components became so complex and interconnected that gene transfer stopped. At this point, which he calls the "Darwinian threshold," organisms became less cooperative and followed a more vertical pathway to evolution: Darwin's model of heredity and variation.

Chaotic gene transfer is edged out by what Woese calls a phase change brought on by ever-building complexity. Ribosomal RNA for instance, which has many interacting partners, holds a well-conserved history; the timeline of aminoacyl-tRNA synthetases, with fewer interacting partners, is more clouded by gene-transfer events. "The componentry of the cell can be classified along a spectrum of how interconnected or how well integrated it is into the fabric of the cell," says Woese. Prior to reaching the threshold, a more cooperative environment reigned, what he calls a "boot-strapping process."

One might guess that this cooperative nature belies Darwin's competitive order. Not so, says biochemistry professor W. Ford Doolittle, Dalhousie University, Halifax, Nova Scotia. "The genes are competing like crazy. ... There's no altruism involved here." Doolittle largely agrees with Woese's latest ideas, none of which, he says, are all that new. He and others, however, believe that gene transfer is nearly as prevalent following Woese's threshold. "We think that the overall structure of the prokaryotic world could conceivably owe itself entirely to lateral gene transfer," says Doolittle. Searching for a last common ancestor amid gene-transfer noise like that, however, may be a futile task.

J. Peter Gogarten, professor of molecular and cell biology, University of Connecticut, compares this task to finding "the mitochondrial Eve that never existed and never met the Y-chromosome Adam." He says that the threshold cannot be a strict line where the whole organism crosses, but it might limit the transfer of particular genes. Others believe that the threshold is a more distinct crystallization of the organismal lineages. Charles Kurland, professor of molecular biology emeritus at Uppsala University, Sweden, calls most observed instances of lateral gene transfer after such a threshold a fata Morgana. "You can't broadcast DNA sequences by radio waves," he says, citing long-branch attraction and divergent paths for duplicated genes as alternate explanations for anomalies that many read as gene transfer.

Some take issue with Woese's methodology. Professor Hervé Philippe, University of Montreal, says that over time, repeated substitutions at many nucleotide positions have erased phylogenetic signals even on well-conserved genes like those for elongation factors and ATPase. "What we have done is a reanalysis of these genes using the most slowly evolving positions ... that are less likely to be sensitive to tree reconstruction artifacts." His conclusion: eukaryotes are the tree of life's roots from which archaea and bacteria evolved through simplification while eukaryotes became more complex.3

Photo: Courtesy of National Center for Biotechnology Information
 Lynn Margulis

SAME FOREST, WRONG TREE Using genes as chronometers, some say, gives the molecules too much anthropomorphic weight. "It's an enormous extrapolation to say it's in the tree of life when what it is, is the tree of cytochrome oxidase or it's the tree of 16S ribosomal RNA," says Lynn Margulis, distinguished university professor, University of Massachusetts, Amherst. Margulis and others, who champion an endosymbiotic theory for the eukaryote's origin, say Woese's recent paper belittles such theories. Woese writes, "Biologists have long toyed with an endosymbiotic (or cellular fusion) origin for the eukaryotic nucleus and even for the entire eukaryote." Analyses of eukaryotic translational machinery show a close relationship to archaea. Other eukaryotic proteins have a closer kinship with prokaryotes, suggesting that a past symbiotic relationship gave rise to a chimeric eukaryote.

For Woese, primitive evolutionary time would never have seen such advanced starting components. "They've taken a well-evolved, modern bacterium and a well-evolved archaean and they've put them in the Waring blender and come out with a eukaryotic cell with some hand waving as to how this occurred."

Woese is the hand-waver, says professor Bill Martin. "He's just casually dismissing a huge and substantial body of evidence to indicate that in fact endosymbiosis is a very important factor, possibly for the origin of eukaryotic cells themselves," explains Martin, of Heinrich-Heine Universitaet, Duesseldorf, and the author of the so-called hydrogen hypothesis, which states that an archaebacterium, not a eukaryote, was the first host for primordial mitochondria.4

Martin points out that Woese does not account for energy requirements in the primordial stew of pre-Darwinian-threshold entities. He says a soon-to-be-published hypothesis accounts for these energy requirements, resulting from compartmentation in porous iron sulfide and nickel sulfide matrixes which might have appeared in ancient geothermal vents. These inorganic compartments possibly served as the precursors to cell walls and allowed for the redox reactions that would power the development of mechanisms like those for translation. He agrees that Woese's recent work depicts a useful evolutionary theory for the development of translation, a highly conserved function. But he adds, "Nothing in life is more conserved than compartmentation from the environment."

Not everyone wants to explain the primordial primer. Professor B. Franz Lang, University of Montreal, also studies the evolutionary history of genes, but avoids speculating about life's origins. "It might be easier to test, 'Did life come from Mars?'"

Brendan A. Maher can be contacted at bmaher@the-scientist.com.

References 1. C.R. Woese, "On the evolution of cells," Proceedings of the National Academy of Sciences, 99:8742-7, June 25, 2002.

2. S. Bunk, "Lateral thinking," The Scientist, 15[14]:17, July 9, 2001.

3. P. Forterre et al., "Where is the root of the universal tree of life?" Bioessays, 21:871-9, 1999.

4. W. Martin et al., "The hydrogen hypothesis for the first eukaryote," Nature, 392:37-41, 1998.