Wednesday, November 22, 2006

The Three Domain Hypothesis (part 2)

Jan Sapp sets the tone by outlining the history of bacterial classification and phylogenetic analysis. We’re mostly concerned with the fourth era—the one that begins in the 1990's with the publication of the first bacterial genomes.
By the late 1990's, just when the three-domain proposal and the outlines of a “universal phylogenetic tree” were becoming well established, the microbial order based on rRNA was challenged by data from complete genome analysis of bacteria. Phylogenies based on genes other than those for rRNA often indicated different genealogies, and indeed a somewhat chaotic order. The new genomic data also indicated that archaebacteria and bacteria had many genes in common: perhaps they were not that different after all.
Sapp then goes on to discuss the attack on the Three Domain Hypothesis by Ernst Mayr in an oft-quoted PNAS paper (Mayr, 1998). Mayr’s objections have more to do with classification and taxonomy than with any real dispute over the validity of the molecular data. It’s about the fact that Mayr doesn’t like cladistics. He doesn’t want molecular phylogenies to trump visible phenotypes and “common sense” (Mayr’s, of course). Mayr argues that archaebacteria and bacteria both look like bacteria so they should be lumped together in a single prokaryotic empire.

I’m not interested in that debate. If the gene trees say that archaebacteria form a separate domain then that’s good enough for me no matter how much they resemble other prokaryotes. Woese (1998) has published an adequate reply to Mayr.

The real arguments are based on conflicting gene trees and the increasingly obvious similarity between bacteria and archaebacteria at the molecular level. How do we resolve the conflicts between the ribosomal RNA trees and examples of equally well-supported trees from proteins? The first thing that comes to mind is that some of the gene phylogenies are just wrong. They are artifacts of some sort and don’t really represent the history of the genes. Most of the debate on this topic concerns the validity of the SSU trees since they are based on nucleotide sequences. It’s well-known that ribosomal RNA trees are prone to long branch attraction artifacts to a greater extend than trees based on amino acid sequences. It’s also well-known that there are some famous mistakes in rRNA trees.

For the time being, let’s assume that all genes trees are accurate representations of the gene history, bearing in mind that the opponents of the Three Domain Hypothesis are not prepared to concede that point.

Conflicting gene trees then have to be artifacts of a different sort. Some of them will accurately represent the evolution of the species while others will not. The ones that don’t follow the phylogeny of the species will deviate because the genes have a different history. Either they have been transferred singly from one species to another or they have been transferred en masse by some sort of fusion event. Sapp discusses both these possibilities.

Lateral gene transfer (LTG)—also called horizontal gene transfer (HGT)—is the latest fad in microbial evolution. You can explain away all the conflicting gene phylogenies by invoking interspecies transfer. But here’s the problem: which genes were transferred and which ones represent the “true” species phylogeny? Several papers in the book address this problem and we’ll cover them in separate postings.

Keep in mind that LGT can get you out of a messy situation but there’s a price to pay. If you envisage a time when cells were frequently swapping lots of genes to form a “net” of life, then that, in and of itself, is enough to refute the standard version of the Three Domain Hypothesis. What you’re left with is a hypothesis about the phylogeny of “some” genes and a different phylogeny for others. This gets us into playground fights about “my gene is better than your gene.” Supporters of the Three Domain Hypothesis are willing to go there in order to save the hypothesis. Do their arguments hold up?

The other way of explaining the conflict is to invoke whole genome fusions followed by selective loss of half the genes. There are several models to explain the origin of eukaryotic cells by fusion of a primitive archaebacterium with a primitive bacterium. Such an event would account for the data, which shows that most eukaryotic genes are more closely related to bacteria but some are closer to archaebacteria. There are other interesting models, for example one model postulates fusion of a primitive eukaryotic cell with a primitive bacterial cell to form the first archaebacterium! This also accounts for the data but it pretty much wipes out one of the three domains!

Most people take these fusion models seriously. If one of the fusion models is correct, then the original Three Domain Hypothesis is refuted. (One of the complications is the transfer of genes from mitochondria to the eukaryotic nucleus. We’re not talking about those genes. Those ones are relatively easy to recognize.)

Jan Sapp closes his introduction with a summary of the problems that will be addressed in the rest of the book.
... with the development of genomics, the hitherto unappreciated ubiquity of LGT was postulated to explain many gene histories other than those for rRNA. The species concept was again considered to be inapplicable to bacteria, not because of the absence of genetic recombination, as long thought, but because there seemed to be so little barrier to it. Doubts about the inability to construct bacterial genealogies arose anew because of the scrambling of the genetic record from LGT. While debates continue over which (if any) provide the most reliable phylogenetic guide, so too do debates over the origin of the eukaryotic cell nucleus and over the inheritance of acquired bacterial genomes.


Microbobial Phylogeny and Evolution: Concepts and Controversies Jan Sapp, ed., Oxford University Press, Oxford UK (2005)
Jan Sapp The Bacterium’s Place in Nature
Norman Pace The Large-Scale Structure of the Tree of Life.
Woflgang Ludwig and Karl-Heinz Schleifer The Molecular Phylogeny of Bacteria Based on Conserved Genes.
Carl Woese Evolving Biological Organization.
W. Ford Doolittle If the Tree of Life Fell, Would it Make a Sound?.
William Martin Woe Is the Tree of Life.
Radhey Gupta Molecular Sequences and the Early History of Life.
C. G. Kurland Paradigm Lost.


Mayr, E. (1998) Two Empires or Three? Proc. Natl. Acad. Sci. USA 95:9720-0823.

Woese, C. R. (1998) Default taxonomy: Ernst Mayr’s view of the microbial world. Proc. Natl. Adad. Sci. USA 95:11043-11046.


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