VIRUSES: IMPORTED GENETIC SOFTWARE

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VIRUSES: IMPORTED GENETIC SOFTWARE
Viruses today spread genes among bacteria and humans and other cells, as they always have... We are our viruses — Lynn Margulis, 1998 (0)
May we not feel that in the virus, in their merging with the cellular genome and their re-emerging from them, we observe processes which, in the course of evolution, have created the succesful genetic patterns that underlie all living things? — Salvador Luria, 1959 (.5)

Herpesvirus by Linda Stannard via All the Virology on the WWW
The neo-Darwinian paradigm holds that copying mistakes and the shuffling of existing genes are sufficient to write the new genes needed for evolutionary advances. Cosmic Ancestry holds that these processes cannot write useful new genes. Instead, for a species to evolve, new genes must first be installed into its genome from outside. We will discuss well-known processes which can install new genes into the genome of a given species. Then we will look at viruses.
Recombination

Mutation is the mechanism of genetic change that we hear the most about. Every known example of mutation, however, is either neutral or deleterious in its effect. The rare exception is the back-mutation, which merely undoes the damage of a previous mutation and restores the affected strand of DNA to its original condition.
Recombination is a much more powerful way for DNA to change. If an organism's genome were written out as text, mutations would be single-letter mistakes, whereas recombination takes whole words, sentences, paragraphs, pages or groups of pages and moves them to different locations. These new locations could be elsewhere in the same paragraph, page, bookshelf, or library. Obviously a powerful mechanism like recombination should be incorporated into anyone's understanding of the theory of evolution. There are three kinds of recombination:

When two strings of similar DNA line up with each other and swap sections, it's called homologous recombination.
When shorter pieces of similar DNA line up to initiate a swap of longer, dissimilar pieces (of which the shorter pieces can be part), that's called site-specific recombination.
Transposition enables a piece of DNA to move within the same chromosome, or to a different chromosome, to a location with which it has no similarity.

The Transfer of DNA Across Species Boundaries

Bacteria trade genes more frantically than a pit full of traders on the floor of the Chicago Mercantile Exchange — Lynn Margulis and Dorion Sagan (1)

While recombination moves whole blocks of genetic instructions within a cell, other processes move whole blocks of genetic information from one bacterium to another bacterium of a different kind. In the analogy between genes and written text, this move is a transfer of paragraphs or pages from one library to another.

One such process is transformation. Here pieces of genetic instructions are released by a bacterium into its environment. Another bacterium, not necessarily of the same strain, picks up the DNA and incorporates it into its own genome. For example, Streptococcus pneumoniae that are not pathogenic can become so by transformation (2). As an illustration of transformation, think of a passenger who jumps overboard from one ship and is later picked up by another one.

Conjugation is the bacterial version of sex. In conjugation, bacterial cells actually connect, and the "male" donates a piece of DNA to the "female." The piece of DNA in this case was excised earlier from the bacterial chromosome. Such excised pieces of DNA are called plasmids. (Plasmids, being able to pass out of one cell and into another, are similar to viruses. But they have no protein coat and no "life cycle" different from that of their host cell; in this respect they resemble small chromosomes.) If the transferred genetic material is a passenger on a ship, in the transfer of plasmids by conjugation the ships come alongside each other and the passenger walks across a gangplank to the new ship.

Transduction is yet another way for bacteria to exchange genetic material. In transduction, a virus takes up a piece of DNA from its bacterial host and incorporates it into its own viral genome. After the virus has multiplied, many copies of the virus erupt from the infected cell. Depending on the kind of transduction, some or all of the daughter viruses take copies of parts of the bacterial DNA with them. When one of them infects a new cell, it inserts the stolen DNA into the new cell, where the stolen piece becomes integrated into the new cell's DNA. (The stolen piece may be a whole gene with which the cell acquires a new function, as was reported in June, 1996, by two scientists at Harvard Medical School (3).) In transduction, the passenger resorts to hiding inside some freight, hoping to get aboard a different ship that way.

Transduction by viruses works in eukaryotic organisms as well. The discovery that large blocks of genetic instructions can be swapped and transferred among creatures is a clue that the insertion of new genes could be the mechanism behind evolution. If viruses can transfer eukaryotic genes across species boundaries, and can install their own genes into their hosts, the case for the new mechanism is even stronger. As we will see, viruses do just that.

Viruses are mobile genetic elements (3.5)

It was an absolutely stunning surprise to us that something as strange as viruses carrying genes from one cell to another can happen — Joshua Lederberg (4)

If your computer suddenly begins to greet you, at various times, with a vulgar message, you will automatically know that the computer has contracted a virus. It might have arrived via the modem, it might have come with a new program on a disk, or someone might have stealthily keyed it in. It might even have been there when you originally acquired the computer. However it got there, it is definitely a computer virus, and your computer did not spontaneously generate it.

Computer viruses are called viruses because they are analogous to real viruses, the ones that infect living cells. Because viruses are simpler than cells, biologists used to think that maybe viruses were the precellular life forms that neo-Darwinism requires. Today even the neo-Darwinists themselves don't think that viruses are this link. Viruses are not independently capable of metabolism or reproduction. Biologists now think that viruses evolved after cells. What is a virus?

T4 virus A virus is a piece of genetic instructions in a protective coat. Virus particles are tiny; a cell can manufacture and contain as many as a thousand of them before breaking open. They were first discovered when biologists observed that some disease-causing agents were able to pass through a filter too fine for bacteria. They can be small because they have almost none of the machinery of a cell, only a smallish quantity of DNA (or RNA) and a protective coat.

Viruses are not living things. When they are outside of their host cell, they are just very complex molecular particles that have no metabolism and no way to reproduce. In our computer metaphor, they're like software with no hardware, floppy disks or diskettes without a computer. Having no independent metabolism they can remain viable indefinitely, under the right circumstances. "Some of them can even be crystallized, like minerals. In this state they can survive for years unchanged—until they are wetted and placed into contact with their particular hosts" (5).

The viruses that infect bacteria are more specifically called bacteriophages, or simply phages. The kind and amount of genetic instructions in phages vary from 3,600 RNA nucleotides to 166,000 DNA nucleotide pairs (6). To restate these dimensions in terms of our computer analogy, the computer viruses that infect handheld calculators range in size from 900 bytes to over 40 kilobytes. For comparison, the simplest handheld calculator (bacterium) has about 200 kilobytes of stored programs.

poliovirus by A. Nicholls via All the Virology on the WWW
The viruses that infect eukaryotic cells vary in size also. The poliovirus has 7,600 RNA nucleotides; the vaccinia (cowpox) virus has 240,000 DNA nucleotide pairs (7). To use computer terms again, the computer viruses that infect personal computers range in size from 1.9 kilobytes to 60 kilobytes. For comparison, a very simple personal computer (a yeast cell) has genetic instructions equivalent to about 8 megabytes. An advanced personal computer (a human cell) contains about 1.5 gigabytes of stored programs, counting the backup copy and the unused programs (silent DNA).

When a virus attaches to its host cell, the host may take the whole virus into its cytoplasm where the virus's protective coat is removed. Some bacteriophages use a different invasion method. They remain outside the cell and a chemical trigger causes them to inject their genome into the host's cytoplasm. Either way, the virus's genome enters the cytoplasm of the host cell.

Once inside, the virus causes the machinery of the host cell to enter one of two cycles, the lytic cycle or the lysogenic cycle. In the lytic cycle, which leads to cell degradation, the host begins to carry out the reproductive instructions in the invading virus's genome. Those instructions are, in summary, "make more of me." The host becomes a slave to the invader; it drops everything and begins to manufacture copies of the virus. After many copies have been made, the cell breaks open and dies, and many viruses are released. This is the normal way in which a virus causes symptoms of disease in its host.

In the lysogenic cycle the host cell does not make more viruses, but simply harbors the entire viral genome in the cell, usually by incorporating it into the cell's genome. If the virus is an RNA virus, as many are, the RNA must first undergo "reverse transcription" into DNA. While harboring the viral genes, the cell may grow and multiply normally, carrying the new instructions harmlessly along with it. A virus carried in this manner is said to be latent. Recently scientists have learned that even during latency, some of the virus's genes can be expressed (8).

Transduction
Sometimes after lysogenic integration of the viral genome into the host's DNA, an "induction event" can cause the viral infection to revert to the lytic cycle, in which the cell makes many copies of the virus and dies. After this happens, the numerous new virus particles can then infect many other cells. If the new infections are lysogenic, the virus's genes may again become integrated into the DNA of the new cells without harm to them. Lytic infection of one host followed by such lysogenic infection in another is also called transduction. When we discussed transduction earlier, we said viruses could tranduct a cell's genes to another cell. Here we see that the virus's own genes can also be transducted into cells.

This method of acquiring genes is not in doubt. Among bacteria, for example, "There are some well-documented cases of homologies between viral genes and their host counterparts. ...Some past exchanges have occurred between distantly related phages and between phage and host" (9). Eukaryotes are also known to acquire viral genes, and the phenomenon is not rare. "Endogenous retroviruses and retroviral elements have been found in all vertebrates investigated.... As a general rule, the number of groups of viral sequences found within a given vertebrate species is proportional to the effort spent searching that species" (9.5).

And it has now been shown that some of the genes that viruses install have a beneficial function for the host. In fact, doctors now use viruses to install genes in the new field of "gene therapy." Even the virus that causes AIDS, if properly disabled, may become useful this way (10, 10.1).

When the genome of Bacillus subtilis was completely sequenced and published in July, 1997, the sequencers noticed another interesting example of gene transfer. "...Some of the bacteriophages in B. subtilis also appear to contribute genes that aid the host bacterium by helping it resist harmful substances such as heavy metals" (11). This evidence confirms that genes installed by a virus into the genome of the host can be beneficial, even essential, for the evolution of the host.

One example of a benefit conferred by viral genes comes from humans. A sequence installed by a retrovirus regulates the amylase gene cluster, allowing us to produce amylase in our saliva. This sequence that we share with a few other primates enables us to eat starchy foods we otherwise couldn't (12.5).

In August, 1997, another whole-genome sequencing, of Helicobacter pylori, found that many genes in it are more similar to those of eukaryotes or archaea than other bacteria (12). "Such observations... are often interpreted as evidence of lateral gene transfer in the evolutionary history of an organism," say the sequencers.

Additional evidence that genes can move across species boundaries even in eukaryotes comes in the June 13, 1997, issue of Science. A report there by Frederico J. Gueiros-Filho and Stephen M. Beverley of Harvard describes the "Trans-kingdom Transposition" of a gene-size piece of DNA known as a transposable element (13). The particular transposable element they studied, called mariner, has already been found in planaria, nematodes, centipedes, many insects, and humans (14). Until recently, transposable elements were considered to be functionless, or "junk DNA." But John McDonald, a professor in the department of genetics at the University of Georgia, concludes, "It now appears that at least some transposable elements may be essential to the organisms in which they reside. Even more interesting is the growing likelihood that transposable elements have played an essential role in the evolution of higher organisms, including humans" (15). Another team of biologists has demonstrated that by transformation (discussed above in bacteria) a mariner element can become installed into the inherited genome of zebrafish (16). So viruses are not the only mobile genetic elements.

In conclusion, viruses could easily provide a way for new genes never before encountered by a species to become part of its genome. That viruses install new genes into their hosts is not speculative — it is a well known fact. That transferred genes are important in evolution is becoming well established. According to Cosmic Ancestry, the horizontal transfer of genes by viruses and other means is essential for evolution.

References

0. Margulis, Lynn. Symbiotic Planet: A New Look at Evolution. Basic Books, 1998. p 64.

.5. Luria, Salvador E. Virus Growth and Variation, A. Isaacs and B.W. Lacey, eds., Cambridge University Press, 1959. p 1-10.

1. Margulis, Lynn and Dorion Sagan. What Is Life? Simon and Schuster 1995. p 73.

2. Campbell, Neil A. Biology, 3rd edition. The Benjamin/Cummings Publishing Company, Inc. 1993. p 301.

3. Waldor, Matthew K. and John J. Mekalanos. "Lysogenic Conversion by a Filamentous Phage Encoding Cholera Toxin" p 1910-1914 v 272 Science. June 28, 1996. Also see comments by Nigel Williams, p 1869-1870; and see "Harvard researchers find cholera bacterium may take instruction from a virus," by Misia Landau and Keren McGinity at EurekAlert!, June 27, 1996.

3.5. Alberts, Bruce; Dennis Bray; Julian Lewis; Martin Raff; Keith Roberts and James D. Watson. The Molecular Biology of the Cell, 3rd edition. New York: Garland Publishing, Inc. 1994. p 274.

4. Lederberg, Joshua. "Interview with Prof. Lederberg, Winner of the 1958 Nobel Prize in Physiology and Medicine," conducted by Lev Pevzner, March 20, 1996. An Internet transcript is available.

5. Margulis, Lynn and Karlene V. Schwartz. Five Kingdoms, 2nd edition. W. H. Freeman and Company 1988. p 16.

6. Brown, T.A. Genetics: A Molecular Approach, 2nd edition. Chapman and Hall 1992. p 221.

7. Brown, T.A. Genetics: A Molecular Approach, 2nd edition. Chapman and Hall 1992. p 234.

8. Baserga, Susan J. and Joan A. Steitz. "The Diverse World of Small Ribonucleoproteins" p 359-381. The RNA World, R.F. Gesteland and J.F. Atkins, eds. Cold Spring Harbor Laboratory Press 1993. p 374.

9. Campbell, Allan M. "Bacteriophage Ecology, Evolution and Speciation" p 81-83 Encyclopedia of Virology, Robert G. Webster and Allan Granoff, eds. Academic Press. 1994.

9.5. Coffin, John M.; Stephen H. Hughes and Harold E. Varmus, eds. Retroviruses, Cold Spring Harbor Laboratory Press, 1997. p 346.

10. Cohen, Jon. "A New Role for HIV: A Vehicle For Moving Genes Into Cells" p 195 v 272 Science. 12 April 1996.

10.1. Pollack, Andrew. "Scientists Enlist H.I.V. to Fight Other Ills" The New York Times. 19 January 1999.

11. Williams, Nigel. "Gram-Positive Bacterium Sequenced" p 478 v 277 Science. 25 July 1997.

12. Tomb, Jean-F., et al. (41 others). "The complete genome sequence of the gastric pathogen Helicobacter pylori" p 539-547 v 388 Nature. 7 August 1997.

12.5. Coffin, John M.; Stephen H. Hughes and Harold E. Varmus, eds. Retroviruses, Cold Spring Harbor Laboratory Press, 1997. p 403.

13. Gueiros-Filho, Frederico J. and Stephen M. Beverley. "Trans-kingdom Transposition of the Drosophila Element mariner Within the Protozoan Leishmania" p 1716-1719 v 276 Science. 13 June 1997.

14. Hartl, Daniel L. "Mariner Sails into Leishmania" p 1659-1660 v 276 Science. 13 June 1997.

15. Williams, Phil. "Transposable Elements May Have Had A Major Role In The Evolution Of Higher Organisms" at EurekAlert!, 9 February 1998.

16. Fadool, James M.; Daniel L. Hartl and John E. Dowling. "Transposition of the mariner element from Drosophila mauritiana in zebrafish" p 5182-5186 v 95 n 9 Proceedings of the National Academy of Sciences of the USA. 28 April 1998.