Evolution of Retroviruses: Fossils in Our DNA1

Article excerpt

UNIQUE AMONG INFECTIOUS AGENTS, retroviruses provide the opportunity for studying their own evolution, evolution of the host-virus relationship, and evolution of the host. This utility stems from the property that retroviruses must, as a normal and essential part of every cycle of replication, cause their genetic information, in the form of a DNA molecule called the provirus, to be joined with, or integrated into, the permanent genetic information of the host cell (figure 1). In a sense, the provirus becomes a gene that codes for the RNA and protein components of the virus, that can persist as long as the cell survives, and that will be passed on to the descendants of that cell as it divides. If this process occurs in a germ line cell (the precursor of a sperm or egg), then all cells of the progeny derived from this cell will contain the provirus, which will then be passed on as an endogenous provirus to the descendants of the individual in whom the infection took place, and can, sometimes, become fixed in the species as a whole. Although all viruses, including retroviruses, evolve very rapidly and frequently appear in and disappear from the species they infect, changes in the genomic DNA of a species take place very slowly. For example, humans and chimpanzees, which diverged from a common ancestor some 5 million years ago, differ in their genome DNA sequences by only a few percent. Analogous to bones of extinct species fixed in geologic strata, proviruses fixed in the germ line can provide us with a fossil record of viruses long extinct in the population. As in the case of fossil shells and bones in stone, reading the record of proviruses fixed in our DNA requires the application of paléontologie reasoning: The record is necessarily incomplete, and has suffered damage from the sands of time in the form of deletion, recombination, and mutation. This damage is not necessarily a bad thing for the interested scientist. As with fossils used to understand the geologic history that has shaped our planet, changes that have happened to fossil retroviruses can also provide valuable indicators for understanding the evolutionary history that has shaped our genome. As I will explain in subsequent sections of this paper, our ability to read the record in this way stems from specific properties shared by all retroviruses.


Studies on the coexistence of viruses (and other infectious agents) with their host species have implied the kind of process cartooned in figure 2. A well-evolved host-virus relationship, in general, allows efficient infection and spread of the virus without causing sufficient morbidity or mortality to significantly impair the function of the host in this process. In some cases, the relationship may be completely without pathogenic consequences; in others, there may be relatively limited disease (such as common cold, warts, gastrointestinal symptoms) from which the host recovers fully; in still others there might be severe disease (such as rabies or influenza) that might lead to the death of the host, but, at the same time, promote the spread of the virus. Genetic factors that affect this process tend to be highly species-specific, so that transmission of a virus into a new species is often associated with considerable morbidity and mortality. Indeed, most of the time this morbidity and mortality will lead to extinction of the virus in the new species, so that most emerging viruses (Ebola is a good example) rapidly disappear from the new host. In the rare case, the virus will be able to spread in the host at a rate sufficient to ensure its survival. In this instance, pathogenic effects unrelated to transmission efficiency will put considerable selective pressure on both host and virus in the direction of a more benign relationship, and genetic changes in both host and virus that contribute to reduced pathogenicity will be selected. Following transmission to a third species, however, the process will, most likely, begin again. …


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