Oct. 15, 1999 ATHENS, Ga. -- Viruses are Trojan Horses, reproducing in animals and plants with sometimes deadly consequences. Since viruses can't reproduce by themselves, they exploit living host cells and use them to produce viral nucleic acid and proteins, then reassemble these into new virus particles.
Particularly dangerous are retroviruses, which use an enzyme called reverse transcriptase to copy themselves into host genomes and replicate. Only recently did scientists discover that a complex retrovirus they named Human Immunodeficiency Virus or HIV caused AIDS. A new study by geneticists at the University of Georgia, however, argues that retroviruses may have been lurking around in animal genomes for millennia.
"It's like thinking that we discovered the use of tools as humans rather recently and then finding out that ancient primates used them, also," said Dr. John McDonald, head of the genetics department. "Scientists had thought that complex retroviruses evolved recently, but our work indicates a possible ancient origin."
The study, led by doctoral student Nathan Bowen, is being published this week in the journal Genome Research.
Retroviruses and related free-moving pieces of genetic material called retrotransposons are extremely important in the genetic makeup of plants and animals, despite the fact they were not discovered until about 50 years ago. For example, half of the maize genome is made up of retroelements, and in some plants such as wheat and pine trees, 90 percent of the genome may be constructed around these "movable genes."
Researchers now believe that these "retroelements" are major causes of genetic mutations and are significant factors in genome evolution. McDonald's laboratory and several others are using the relatively new science of genomics to study how these elements have changed plants and animals. By analyzing the sequences of nucleic acids in certain genomes, they can better understand which retroelements have been highly conserved through species and over time.
Which brings us to worms.
McDonald and Bowen had the advantage of studying the near-complete genome for a tiny unsegmented and transparent worm called Caenorhabditis elegans, commonly known as the nematode. These worms, which are both free-living and parasitic, live almost everywhere, though they flourish in rotting vegetation in many parts of the world.
Hundreds of scientists are studying C. elegans around the globe. Though it is a somewhat primitive organism, it shares many of the essential characteristics of human biology. Scientists consider C. elegans to have a "brain," and it exhibits behavior and is even capable of rudimentary learning. Its life starts with embryonic cleavage, it grows and develops, ages and dies. All of these functions are controlled by genes. The worms are no more than one millimeter long and live only two or three weeks.
And yet they have become enormously important to scientists, especially geneticists, and two teams are nearing completion of the sequence of all the genes in C. elegans, showing where each gene is located on a chromosome and its likely function. McDonald and Bowen were thus able to use the C. elegans genome sequence to analyze the entire complement of retrotransposons in the worm's genome.
"We analyzed a class of elements called long terminal repeat retrotransponsons or LTR retrotransposons," said Bowen, "and we found that there are no less than 12 distinct families of them in the C. elegans genome. "These include one novel family that displays many features characteristic of complex vertebrate retroviruses such as the spumaviruses and the lentiviruses, to which HIV belongs. This unexpected finding suggests that infectious vertebrate retroviruses may have a remarkably long ancestry and may have been components of ancient eukaryotic genomes." (Eukaryotes are organisms composed of one or more cells that contain well-defined nuclei.)
This biological detective story began with programs that are used to identify and align the sequences of amino acids so they can be compared. Bowen and McDonald studied 12 families of LTR transposons in C. elegans named "Cer elements." Since they knew already that the reverse transcriptase (an enzyme, remember) domains have the slowest rate of change among all retroelement proteins, they could look to these areas for clues to the evolutionary relationships among retroelements.
"We quickly focused on an element we called Cer7, which displays many of the features of retroviruses," said Bowen. "We found there are many structural similarities between Cer7 and other retroviral proteins." In fact, Cer7 has features similar to complex vertebrate retroviruses such as the human T-cell leukemia/bovine leukemia group and the lentiviruses such as HIV.
So what? The finding is significant because the retroviral-like Cer7 is in a worm, and researchers had previously believed that complex retroviruses had originated about the same time as mammals.
"Our findings suggest that the ancestor of vertebrate retroviruses may have had an early metazoan origin," said Bowen.
While the discovery of the possible ancient origin for vertebrate retroviruses is significant, the paper in Genome Research goes even farther, proposing a new LTR retroelement nomenclature. New classes and subgroups show the relations among retroelements much more clearly, the authors assert. (A color slide of the new phylogeny is available on request from the authors.)
"The genome sequencing of model experimental organisms like C. elegans and humans is providing an unprecedented opportunity to examine the evolutionary relationships that exist among retroelements," said McDonald. "The presence in C elegans of elements displaying a number of characteristics previously thought to be unique to vertebrate retroviruses suggests an ancient lineage for this important class of infectious agents."
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