Origin of Viruses (2024)

According to this hypothesis, viruses originated through aprogressive process. Mobile genetic elements, pieces of genetic materialcapable of moving within a genome, gained the ability to exit one cell andenter another. To conceptualize this transformation, let's examine thereplication of retroviruses, the family of viruses to which HIV belongs.

Retroviruses have a single-stranded RNA genome. When thevirus enters a host cell, a viral enzyme, reverse transcriptase, converts thatsingle-stranded RNA into double-stranded DNA. This viral DNA then migrates tothe nucleus of the host cell. Another viral enzyme, integrase, inserts thenewly formed viral DNA into the host cell's genome. Viral genes can then betranscribed and translated. The host cell's RNA polymerase can produce newcopies of the virus's single-stranded RNA genome. Progeny viruses assemble andexit the cell to begin the process again (Figure 2).

This process very closely mirrors the movement of animportant, though somewhat unusual, component of most eukaryotic genomes: retrotransposons.These mobile genetic elements make up an astonishing 42% of the human genome(Lander et al. 2001) and can movewithin the genome via an RNA intermediate. Like retroviruses, certain classesof retrotransposons, the viral-like retrotransposons, encode a reversetranscriptase and, often, an integrase. With these enzymes, these elements canbe transcribed into RNA, reverse-transcribed into DNA, and then integrated intoa new location within the genome (Figure 3). We can speculate that theacquisition of a few structural proteins could allow the element to exit a celland enter a new cell, thereby becoming an infectious agent. Indeed, the geneticstructures of retroviruses and viral-like retrotransposons show remarkablesimilarities.

In contrast to the progressive process just described,viruses may have originated via a regressive, or reductive, process.Microbiologists generally agree that certain bacteria that are obligateintracellular parasites, like Chlamydiaand Rickettsia species, evolved fromfree-living ancestors. Indeed, genomic studies indicate that the mitochondriaof eukaryotic cells and Rickettsiaprowazekii may share a common, free-living ancestor (Andersson et al. 1998). It follows, then, thatexisting viruses may have evolved from more complex, possibly free-livingorganisms that lost genetic information over time, as they adopted a parasiticapproach to replication.

Viruses of one particular group, the nucleocytoplasmiclarge DNA viruses (NCLDVs), best illustrate this hypothesis. These viruses,which include smallpox virus and the recently discovered giant of all viruses,Mimivirus, are much bigger than most viruses (La Scola et al. 2003). A typical brick-shaped poxvirus, for instance, maybe 200 nm wide and 300 nm long. About twice that size, Mimivirus exhibits atotal diameter of roughly 750 nm (Xiao etal. 2005). Conversely, spherically shaped influenza virus particles may beonly 80 nm in diameter, and poliovirus particles have a diameter of only 30 nm,roughly 10,000 times smaller than a grain of salt. The NCLDVs also possesslarge genomes. Again, poxvirus genomes often approach 200,000 base pairs, andMimivirus has a genome of 1.2 million base pairs; while poliovirus has a genomeof only 7,500 nucleotides total. In addition to their large size, the NCLDVsexhibit greater complexity than other viruses have and depend less on theirhost for replication than do other viruses. Poxvirus particles, for instance,include a large number of viral enzymes and related factors that allow thevirus to produce functional messenger RNA within the host cell cytoplasm.

Because of the size and complexity of NCLDVs, somevirologists have hypothesized that these viruses may be descendants of morecomplex ancestors. According to proponents of this hypothesis, autonomousorganisms initially developed a symbiotic relationship. Over time, therelationship turned parasitic, as one organism became more and more dependenton the other. As the once free-living parasite became more dependent on thehost, it lost previously essential genes. Eventually it was unable to replicateindependently, becoming an obligate intracellular parasite, a virus. Analysisof the giant Mimivirus may support this hypothesis. This virus contains arelatively large repertoire of putative genes associated with translation — genes that may be remnants of a previously complete translation system. Interestingly,Mimivirus does not differ appreciably from parasitic bacteria, such as Rickettsia prowazekii (Raoult et al. 2004).

The progressive and regressive hypotheses both assume thatcells existed before viruses. What if viruses existed first? Recently, severalinvestigators proposed that viruses may have been the first replicatingentities. Koonin and Martin (2005) postulated that viruses existed in a precellularworld as self-replicating units. Over time these units, they argue, became moreorganized and more complex. Eventually, enzymes for the synthesis of membranesand cell walls evolved, resulting in the formation of cells. Viruses, then, mayhave existed before bacteria, archaea, or eukaryotes (Figure 4; Prangishvili et al. 2006).

Most biologists now agree that the very first replicatingmolecules consisted of RNA, not DNA. We also know that some RNA molecules,ribozymes, exhibit enzymatic properties; they can catalyze chemical reactions.Perhaps, simple replicating RNA molecules, existing before the first cellformed, developed the ability to infect the first cells. Could today'ssingle-stranded RNA viruses be descendants of these precellular RNA molecules?

Others have argued that precursors of today's NCLDVs ledto the emergence of eukaryotic cells. Villarreal and DeFilippis (2000) and Bell (2001) describedmodels explaining this proposal. Perhaps, both groups postulate, the currentnucleus in eukaryotic cells arose from an endosymbiotic-like event in which acomplex, enveloped DNA virus became a permanent resident of an emerging eukaryoticcell.