The Caveat of Horizontal Transfer

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What is the point?

  1. To be able to describe why horizontal transfer is a difficultly that phylogenetic analysis must deal with.
  2. To be able to describe the perspective that horizontal transfer is an important aspect of molecular evolution of asexual organisms, but does not invalidate the notion of a phylogeny of these organisms.
  3. To be able to describe how the end of rampant horizontal transfer may have lead to the emergence of the three Domains.

The fly in the ointment of molecular phylogenetic analysis, especially in attempts to sort out its deepest parts, is the issue of horizontal transfer. The trees we've been talking about are based in ssu-rRNA, and these are substantiated by a number of other highly conserved genes. However, we know that genes have "moved" from one organism to another across phylogeny - in fact, gene flow at about the species level is probably the most common source of phenotypic variation in Bacteria. But horizontal transfer isn’t limited to near-relatives; genes on rare occasions have moved across the farthest reaches of the tree. The most substantial examples of this are the movement of bacteria genomes into eukarotes in the endosymbioses that resulted in the mitochondria and chloroplasts. Most of the genes of these organelles, especially mitochondria, have moved to the nucleus.

Dolittle tree

Schematic view of the "Tree of Life", incorporating horizontal gene transfer (W. Ford Dolittle)

Horizontal transfer can be divided into two basic types: intra-specific (between close relatives) and inter-specific (between distant relatives).

Intraspecific recombination

In sexually-reproducing plants and animals, species are defined as breeding populations - groups of individuals that are capable of producing viable, fertile offspring. In Bacteria, Archaea, and many eukaryotes, reproduction and genetic exchange (sex) are not linked. However, Bacteria and Archaea do exchange DNA amongst members of a population of related individuals by intraspecific recombination. DNA is transferred by transducing phage, conjugative plasmids, and direct uptake from the environment (presumably from lysed cells), and this DNA is incorporated into the chromosome by homologous recombination. This is generally specific to closly-related organisms because homologous recombination demands that the sequences be very similar. Many organisms naturally take up DNA from the environment, either non-specifically or by specific recognition of DNA sequence tags that indicate that the DNA is from the same specie.

The advantages of intraspecific recombination is the same as for sexual reproduction - alleles are shuffled, allowing those that are favorable under the circumstances to combine with other genetic backgrounds or favorable alleles without having to re-invent them from scratch, or to lose their connection with dis-advantageous alleles in their 'home' genome.

Distant-species gene transfers

It is also clear that DNA sequences have moved large phylogenetic distances, such as the genes in Thermotoga that seem to come from Archaea. But there are plenty of other examples:

  • genes from the progenitors of chloroplasts and mitochondria have mostly been moved to the nucleus, although some remain in the organelle.
  • Antibiotic resistance genes; we've already talked about this.
  • An importance instance of cross-species gene transfer is pathogenicity islands. These are regions of DNA containing gene important for virulence that appear to come and go in the genomes of many pathogenic Bacteria. For example, the major difference between enteropathogenic E. coli and innocuous E. coli is the presence or absence of a large pathogenicity island. In this particular case the mystery is even deeper, because this pathogenicity island also contains a large chunk of DNA, with no genes of known function, from cyanobacteria!
  • Movement of proteorhodopsin amongst all kinds of oceanic Bacteria
  • and many others....

These seem to occur at rates that are many, many orders of magnitude lower than for intraspecific transfer, but over evolutionary time scales are very significant.

A special case of lateral gene transfer is cell fusion, or hybridization, when the cells of different kinds of organisms fuse, including their genomes, creating a new kind of organism. This is a well-known process in the plant world, but there are probably cases of it in microbes as well.

What impact does horizontal transfer have for "The Big Tree"?

The answer to this is not yet clear. Horizontal transfer is a contentious issue, and a lot of contention is because of historical baggage. For a long time, horizontal transfer was a ready excuse used, without evidence, for any unexpected gene in an organism. As a result, the notion of horizontal transfer acquired a bad name; it was seen as thoughtless hand-waving. When ssu-rRNA trees began to revolutionize how we thought about microbial evolution, the focus was on understanding general phylogenetic relationships, and the issue of horizontal transfer was set aside as being sufficiently rare to be not significant in the evolution of these organisms. But then genome sequences began to become available, and it became clear that horizontal transfer is a general and significant aspect of microbial evolution, and some scientists went so far (as the pendulum swung) as to declare that phylogenetic relationships are meaningless for Bacteria and Archaea; that every gene in an organism has its own evolutionary history and that microbes as a whole are just transient subsets of a big “prokaryotic” gene pool. The notion of “species” of Bacteria and Archaea is meaningless in this view. This remains a topic of harsh argument and personal attacks.

But it seems most likely that although horizontal transfer is a big factor in the evolution of microbes, there is a core of the genome that generally reflects the vertical evolution of the organism. This core is predominantly the genes for the "central dogma" of the cell; in other words, the information-processing system. In contrast, genes for metabolism (and therefore phenotype) seem to be far more susceptible to horizontal transfer. Since these are the things we see and measure about an organism, these are certainly important.

But if the properties of an organism can move horizontally, does that mean that phylogeny is meaningless? Not in my view. When a gene is acquired from some other source by an organism, it begins the rapid process of adapting to it's new genetic environment; in other words, it quickly becomes part of the organism it now resides in. Horizontal transfer is just another source (perhaps the biggest source) of the genetic variation that Darwinian evolution requires.

The SevenI have a old classic car, a 1968 Lotus Super Seven. Over the past 43 years, most of this car has been replaced at one time or another; some parts several times. Yet, according to the North Carolina Department of Motor Vehicles, it is still a 1968 Super Seven. Why? Because every time a new part (or collection of parts) was put in, it had to be incorporated into the existing car. Even replacing the engine (which has been done) or major chunks of the framework (ditto) doesn't void the overall ancestry of the machine. Replacing the generator with the alternator from a Jaguar changed the behavior of the system, and gave it new capabilities, but doesn't make the car specifically Jag-like. Likewise, the material your body is made of cycles in and out on average every 7 years; does this mean you aren't the same individual? Does this mean that adults don't have a meaningful mother or father? Of course not.

The current task, then, at least in my view, is to not throw the baby out with the bathwater, and come up with a theory of microbial species and evolutionary history that incorporates both vertical and horizontal inheritance. This is probably the single most important theoretical problem in Microbiology today. Remember that "The Origin of Species" by Charles Darwin, and everything that has flowed from it, originated from trying to understand what a "species" really is in the macroscopic world. What will we learn from a much-needed understanding of microbial species - the organisms that predominate our world?

Dolittle Tree of Life
The Dolittle Tree of Life, adapted by Perdita Phillipsfrom an image by Jana Brenning in Uprooting the Tree of Life, J. Ford Dolittle

Here is the Dolittle tree again, colorized to highlight the main "trunks" of the tree containing the bulk of the genes. These represent the main lines of descent, and you can easily see the 3 Domain tree it reveals. The original image was intended to emphasize horizontal transfer, but the cross-branches represent a minority of genes compared to the main lines of descent. If this tree were drawn with the thickess of the branches representing genetic content, it might convey a very different picture.

Horizontal transfer and the origin of the Domains from the Last Common Ancestor

There is reason to believe that horizontal transfer was more common in the deep past, before the emergence of the three Domains, than it is today. In fact, the emergence of the Bacteria, Archaea, and Eukarya from their common ancestor may actually represent the emergence of more-or-less independently evolving lineages from a prior amalgamated gene pool. Perhaps those who think that microbes exist as a continuous gene pool are correct after all, but only for organisms before the emergence of distinct lineages and the three Domains. Notice on the tree above that the three Domains emerge from a network of branches, and that ancestry gets harder to distinguish the deeper in the tree you get. The last common ancestor probably was not a specific organism, or even species, but a communal system with very different evlutionary properties than those of modern organisms.

(By the way, the same sort of arguement from a tree network can be used to show that there was no meaningful "mitochondrial Eve". The last common ancestor of humans, following the mitochondrial genes and therefore the maternal lineage, was no doubt an unexceptional female member of the breeding population of proto-humans. Only chance resulted in her, and only her, mitochondrial lineage persisting into the far future. Nothing at the time, or for a long time thereafter, singled our her lineage. It had to be someone.)