Part Human, Part Virus

Mitochondria.jpgA lot of people think of viruses and bacteria in our bodies as nothing more than pests. It's certainly true that a lot of them do an excellent job of making us ill. But some viruses and bacteria merged with our ancestors over the course of billions of years, and if you were to have them removed from your body today, you'd die faster than if you'd gotten a massive dose of Ebola.

In order to breathe, we depend on sausage-shaped blobs in our cells called mitochondria. When I say we, I mean not just humans or animals, but a vast group of species known as eukaryotes, which also includes plants, fungi, algae, slime molds, and various amoeba-like creatures. Mitochondria use oxygen and other chemicals to create the fuel our cells use. When mitochondria were first discovered at the end of the 1800s, many scientists were struck by how much they looked like bacteria. Some even went so far as to say that they were bacteria--that somehow every cell in our body was invaded by oxygen-breathing microbes, providing them shelter in exchange for fuel.

Scientists already knew that other bacteria could live inside animals or plants. Some bacteria live inside cows, where they digest the tough tissues of the grass their hosts eat; the cows then eat some of the bacteria. Still, it was one thing to say that bacteria lived inside our bodies, and another to say that they lived inside our cells.

But meanwhile more bacteria-like things were turning up inside cells. Plants, for example, have a second set of blobs in their cells that they use to carry out photosynthesis. Known as chloroplasts, they capture incoming sunlight and use its energy to combine water and carbon dioxide into organic matter. And like mitochondria, chloroplasts bear a striking resemblance to bacteria. Some scientists became convinced that chloroplasts were, like mitochondria, a form of symbiotic bacteria--specifically, that they descended from cyanobacteria, the light-harnessing microbes that live in oceans and fresh water.

 Until the early 1960s, the symbiotic theory sputtered in and out of the scientific fashion like a weak flame. But in the 1960s, scientists discovered that mitochondria and chloroplasts have genes of their own. They use their DNA to make their own proteins, and when they duplicate themselves, they make extra copies of their DNA, just as bacteria do. Yet scientists still lacked the tools for finding out exactly what sort of DNA mitochondria and chloroplasts carried. Skeptics suggested their genes had originated inside the nucleus, and at some point evolution had moved it into outlying shelters.

But in the mid-1970s two teams of microbiologists, one headed by Carl Woese of the University of Illinois, and the other by W. Ford Doolittle at Dalhousie University in Nova Scotia, showed that this was not so. They studied the genes inside the chloroplasts of some species of algae, and they found that they bore little resemblance to the genes in the algae's nucleus. Chloroplast DNA, it turns out, is cyanobacteria DNA. In the late 1970s Doolittle's team showed that mitochondria were also bacterial genes, and in the years that followed, other scientists zeroed in on exactly which kind of bacteria they belonged to. In 1998, Siv Andersson of Upsalla University in Sweden and her colleagues discovered the closest relative of mitochondria yet known: Rickettsia prowazekii, a vicious bacteria that causes typhus.

At some point in the distant past, the evidence now indicates, a long-lost oxygen-breathing bacterium gave rise to the ancestors of both Rickettsia and mitochondria. Both lineages were originally free-living microbes, feeding on the nutrients that surrounded them. At some point, each lineage began to live inside other organisms. The ancestors of Rickettsia evolved into a ruthless parasite that could plunge into its hosts and ravage them. But the bacteria that invaded our ancestors ended up in a kinder relationship. Proto-mitochondria may have hung around early eukaryotes to feed on their wastes, and the eukaryotes--which could not use oxygen for their metabolism--came to rely in turn on the wastes of the oxygen-breathing proto-mitochondria. Eventually the two species merged together, and the exchanges between them began to take place with a single cell.

Over time, mitochondria lost a lot of their genes. Although they had once been essential for the free-living ancestors of mitochondria, they now were useless, since their hosts could already take care of a lot of the work involved in staying alive. When these genes were accidentally cut out of the mitochondrial genome by a mutation, the mitochondria (and their hosts) did not suffer. Many other genes became incorporated into the DNA in the nucleus of eukaryotes. Even after these single-celled eukaryotes evolved into much more complex species--oak trees, truffles, people--mitochondria continued to play their essential role. (I go into more detail on all this in my book Evolution.)

The story does not stop here, though. Jonathan Filee and Patrick Forterre, two French biologists, have a paper in press in Trends in Microbiology reporting on some surprising results from their new studies of mitochondrial DNA. Some of the surviving genes in mitochondria produce enzymes whose job it is to build new mitochondrial DNA, as well as RNA, a single-stranded version of DNA that acts as a genetic messenger among other jobs. Unlike the rest of the genes in mitochondria, these DNA and RNA-building genes don't resemble the corresponding genes of related bacteria. They are genes from viruses.

How did viruses contribute genes that are now essential for our survival? Filee and Forterre searched for the most closely related version of the virus genes in mitochondria. They found that the genes resembled DNA and RNA building genes from a large family of bacteria-infecting viruses called bacteriophages T3/T7. This was a surprising result at first, because T3/T7 viruses that were known at the time were a nasty bunch of parasites that invade bacteria, making a lot of new copies of themselves with the help of their of their hosts' cellular machinery, and then explode out of the bacteria, leaving them to die.

But a continued search brought another surprise. The scientists found the genomes of some T3/T7 viruses stitched into the DNA of some free-living bacteria. So-called "cryptic" viruses are pretty common, and it's likely that they are the result of defective genes that failed to make new copies of them. The invading virus's DNA simply became a harmless part of its host's genome. In many cases, the genes of cryptic viruses have suffered major damage from later mutations and many of their genes have been cut out of their host genomes altogether. But a few remnants still survive, and they're enough to allow Filee and Forterre to get some clues to the origin of the virus genes in our own mitochondria.

Here's the history as they now see it: the free-living, oxygen-breathing ancestors of mitochondria were infected with some nasty T3/T7 viruses. Most of the time the viruses were fatal. But some mutant tried to replicate itself inside a proto-mitochondrion and failed. Its genes were trapped in the genome of its host. Its host was able to reproduce, and one of its descendants took up residence inside the cell of a eukaryote. At some point after this merger, a mutation caused the virus's DNA and RNA copying genes to come back online. They took over the job of making these molecules, and the mitochondria's own genes for this job were later stripped out of its genome.

It's a plausible hypothesis for a number of reasons. Filee and Forterre didn't just pull the notion that viral genes can become active again out of a hat; this sort of viral resurrection has been documented in other species. Not only is the hypothesis plausible, but it's a tantalizing as well. It suggests that we are chimeras built from the DNA of eukaryotes, bacteria, and viruses, all mixed together through a natural version of genetic engineering. Forterre even argues that these sorts of results are going to turn out to be the tip of the iceberg. Like many scientists, he believes that before life was based on DNA, the Earth was inhabited by RNA-based life. He argues that DNA was an invention of viruses of these RNA-based organisms, which the RNA-based organisms then seized for their own use. All this may not make you any fonder of the chickenpox you may have had as a kid, but it may at least give you a feeling of kinship.

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Does this mean I am "Frankenfood"? Are Greenpeace activists in white haz-mat suits going to be protesting me?

Great. Just what I need.

i think that you made all of this up

By creckbaby (not verified) on 15 Sep 2005 #permalink

Once again, you have put together a great precis of a particularly interesting aspect of biology. Your blog goes higher on my MyYahoo pecking order RSS list. Keep up the good work!

Fantastic hypothesis!!! You might be next biological genius like Darwin!

Oh this is just GREAT. You mean I now have to tell my creationist friends that not only are they "slime", they are a "virus"? I don't know, it's getting harder and harder...

A very plausible story indeed, but then so is Michael Crichton's The Andromeda Strain.
His idea came from Gaylord Simson's "The Major Features of Evolution".

You just get done making fun of Michael Medved's anthropomorphic tale of penguin love, and here you go personifying the kinship of genetic material. I can just visualize little virus with horned rim glasses, pocket protector, and clipboard designing their next chimeras.

The personification of genetic material:

"The ancestors of Rickettsia evolved into a ruthless parasite that could plunge into its hosts and ravage them. But the bacteria that invaded our ancestors ended up in a kinder relationship.

"Some of the surviving genes in mitochondria produce enzymes whose job it is to build new mitochondrial DNA, as well as RNA, a single-stranded version of DNA that acts as a genetic messenger among other jobs."

"This was a surprising result at first, because T3/T7 viruses that were known at the time were a nasty bunch of parasites that invade bacteria, making a lot of new copies of themselves with the help of their of their hosts' cellular machinery, and then explode out of the bacteria, leaving them to die."

"It suggests that we are chimeras built from the DNA of eukaryotes, bacteria, and viruses, all mixed together through a natural version of genetic engineering."

"He argues that DNA was an invention of viruses of these RNA-based organisms, which the RNA-based organisms then seized for their own use. All this may not make you any fonder of the chickenpox you may have had as a kid, but it may at least give you a feeling of kinship."

Remember that Star Trek episode where the silicon based Horta mother is protecting
her round silicon eggs from the miner's on Janus VI? Maybe somewhere is the Mother
Virus, protecting here genetic material from foreign invaders. She is kind by nature,
but when those nasty parasites are destroying her offspring, she is ruthless in
protecting them, through her best engineered machinery.

Joel, I hope that was tongue in cheek. You are not seriously suggesting that this article in any way anthropomorphizes the virus? Saying other life "acts like" humans (the penguins) and saying that there is a distant evolutionary relationship (in this case, a virus) is not the same thing. I'm guessing you were being cute, like I was in my earlier post about my creationist friends. That WAS a good Star Trek episode though. Would never have remember that they were called Hortas, but it DOES ring a bell!

It gets even better.

Nearly 50% of your DNA is retroviral in origin (i.e., the retroelements), and much of your DNA consists not simply of the relics of retroviruses, but of endogenous retroviruses in proviral form (30,000 retroviruses per haploid genome = 1-3% of your DNA) -- which is in the same neighborhood as the percentage of coding DNA. Moreover, three of these retroviruses play complementary roles in creating a barrier to the mother's immune system in the placenta, thus protecting the developing embryo -- which would otherwise be recognized as a foreign body by the immune system since it differs genetically from the mother. Moreover, these three are expressed in normal embryonic tissue development in a variety of organs, including the kidneys, testes, lungs, and nervous tissue. Moreover, your haploid genome has approximately fifty copies of a retrovirus which appears to be closely related to HIV-1 -- HERV K. And there is much, much more -- but at present we are probably still just scratching the surface.

By Timothy Chase (not verified) on 16 Sep 2005 #permalink

The information you provide is interesting and usefull. All the various species, and, in a removed sense, even viruses, are a marriage of information and life. So what you describe are outcomes of some extremely complex interacting information technology processes, which have factored into them items such as environmental requirements and efficiency of operation. You are describing something that is mind-blowing. If you wish your writings to become something other than a quaint whimsey, in the eyes of future readers, either admit we don't yet see how this information outcome came about (i.e., admit the mechanisms of evolution are currently little understood) or start looking for the mechanisms. Information outcomes demand information technology. Nothing written above, and nothing in Neo-Darwinism, goes within a light-year of accounting for the information processes that by definition were involved. Biology needs to come to an understanding of technologies such as Quantum Physics, Nanotechnology, Advanced Computation, and so on. Darwin lived in the 19th Century. Regards, P.H..

Great article.

By Danniel Soares (not verified) on 17 Sep 2005 #permalink

Philip Bruce Heywood wrote:

If you wish your writings to become something other than a quaint whimsey, in the eyes of future readers, either admit we don't yet see how this information outcome came about (i.e., admit the mechanisms of evolution are currently little understood) or start looking for the mechanisms. Information outcomes demand information technology. Nothing written above, and nothing in Neo-Darwinism, goes within a light-year of accounting for the information processes that by definition were involved. Biology needs to come to an understanding of technologies such as Quantum Physics, Nanotechnology, Advanced Computation, and so on. Darwin lived in the 19th Century. Regards, P.H..

Ah... yes..., you have to understand everything before you can understand anything. Omniscience is the only guarantee of knowledge.

Empirical science doesn't work that way, friend. And Intelligent Design "theorist" William Dembski's so-called approach to information theory has been thoroughly debunked.

But here are some articles at varying levels which those who are actually interested in science might enjoy:

Human endogenous retroviruses in health and disease: a symbiotic perspective
Frank P. Ryan
J R Soc Med 2004; 97:560-565
December 2004
http://www.rsm.ac.uk/new/pdfs/j_art_dec04.pdf

The role of retroviruses in human life and disease
http://www.medicalnewstoday.com/medicalnews.php?newsid=17320

Human endogenous retroviruses: transposable elements with potential?
P.N. Nelson, P. Hooley, D. Roden, H Davari Ejtehadi, P. Rylance, P.
Warren, J. Martin & P.G. Murray
Clin Exp Immunol 2004; 138:1-9

Beneficial Role of Human Endogenous Retroviruses: Facts and Hypotheses
E. Larson & G. Andersson
Scan. J. Immunol. 48 pp. 329-338
Accepted 15 Jun 1998

The human endogenous retrovirus K Rev response element coincides with
a predicted RNA folding region
Jin Yang, Hal Bogerd, Shu-Yun Le, and Bryan R. Cullen
RNA (2000), 6: p. 1551-1564
www.rnajournal.org/cgi/content/abstract/6/11/1551

Periodic Explosive Expansion of Human retroelements Associated with
the Evolution of the Hominoid Primate
Tae-Min Kim, Seung-Jin Hong, Mun-Gan Rhyu
J Korean Med Sci 2004; 19: 177-85
http://jkms.kams.or.kr/2004/pdf/04177.pdf

'Punctuated' evolution in the human genome
http://www.medicalnewstoday.com/medicalnews.php?newsid=26283

"Five retroelement families, L1 and L2 (long interspersed nuclear
element, LINE), Alu and MIR (short interspersed nuclear element,
SINE), and LTR (long terminal repeat), comprise almost half of the
human genome...."

Constructing primate phylogenies from ancient retrovirus sequences
Welkin E. Johnson and John M. Coffin
Proc. Natl. Acad. Sci.
Vol. 96, pp. 10254-10260, August 1999
http://www.pnas.org/cgi/content/abstract/96/18/10254

Phylogenetic relationships among cetartiodactyls based on insertions
of short and long interersed elements: Hippopotamuses are the closest
extant relatives of whales
Masato Nikaido, Alejandro P. Rooney, and Norihiro Okada
Proc. Natl. Acad. Sci.
Vol. 96 pp. 10261-10266, August 1999
http://www.pnas.org/cgi/content/abstract/96/18/10261

An ancient family of human endogenous retroviruses encodes a
functional homolog of the HIV-1 Rev protein
Jin Yang, Hal P. Bogerd, Sheila Peng, Heather Wiegand, Ray Truant, and
Bryan R. Cullen
Howard Hughes Medial Institute and Department of Genetics
Approved September 28, 1999
http://www.pnas.org/cgi/content/abstract/96/23/13404

Identification of endogenous retroviral reading frames in the human genome
Palle Villesen, Lars Aagaard, Carsten Wiuf and Finn Skou Pedersen
Retrovirology 2004, 1:32
October 2004
http://www.retrovirology.com/content/1/1/32/abstract

The Solitary Long Terminal Repeats of ERV-9 Endogenous Retrovirus Are
Conserved during Primate Evolution and Possess Enhancer Activities in
Embryonic and Hematopoietic Cells
Jianhua Ling, Wenhu Pi, Roni Bollag, Shan Zeng, Meral Keskintepe,
Hatem Saliman, Sanford Krantz, Barry Whitney, and Dorothy Tuan
Journal of Virology,p. 2410-2423, Mar. 2002
http://jvi.asm.org/cgi/content/full/76/5/2410

(Infers the family tree (phylogenetic relationships) for human,
chimpanzee, gorilla, orangatan, gibbon, old world monkeys, new world
monkeys from ERV-9 subfamily divergences)

Insertional polymorphisms of full-length endogenous retroviruses in humans
Geoffrey Turner, Madalina Barbulesu, Mei Su, Michael I. Jensen-Seaman
Current Biology 2001, 11:1531-1535
2 October 2001
http://info.med.yale.edu/genetics/kkidd/403.pdf

HERV-K113 may still be capable of infection

Evolution of Retroviruses: Fossils in our DNA
John M. Coffin
Proceedings of The American Philosophical Society Vol. 148, No.3, pp. 264-280
September 2004
http://www.aps-pub.com/proceedings/1483/480302.pdf

Expressions and Functions of Human Endogenous Retroviruses in the
Placenta: An Update
A. Muir, A. Lever and A. Moffet
Placenta (2004), 25, Supplement A, Trophoblast Research, Vol. 18 S16-S25
Accepted 5 January 2004

Can Viruses Make Us Human?
Luis P. Villarreal
Proceedings of the American Philosophical Scoiety Vol. 148, No. 3,
September 2004, pp. 296-323
http://www.aps-pub.com/proceedings/1483/480304.pdf

The viruses in all of us: Characteristics and biological significance
of human endogenous retrovirus sequences
Roswitha Lower, Johannes Lower, and Reinhad Kurth
Poc. Natl. Acad. Sci USA Vol. 93, pp. 5177-5184
May 1996
http://www.pnas.org/cgi/content/abstract/93/11/5177

By Timothy Chase (not verified) on 17 Sep 2005 #permalink

Thanks! Just a couple weeks ago I had been trying to explain these ideas to a friend of mine. Now I'll have a cogent and extremely easy to follow explanation in writing I can pass on to him (with accreditation, of course).
I'm also going to post the link to this story to a paleoanthropological newsgroup to which I belong. No one really ever takes into account exactly how wild evolution can be.

Michael Burns

By Gerard Michael Burns (not verified) on 17 Sep 2005 #permalink

Thankyou, Mr. Chase. I will check some of those references, although I don't know whether they will or will not assist a layman such as myself in seeing how humans can be descended from monkeys yet not be giving birth to monkeys. When people were building an earth - centered solar system they relied on various celestial bodies to turn in secondary circles whenever and wherever necessary. The solar system would never quite solve, so more and more of these epicycles were added, and as demand for a rational system increased, so did the obfuscating epi's. Eventually, the system began to disappear under the weight of them. One gets the feeling that's about where biology is, now. But I'll try to follow some of the references. P.H..

Estou verdadeiramente fascinado pelo seu livro "Evolução, o triunfo de uma idéia", que acabei de ler.
Parabéns! Eu era um ateu "político", agora posso dizer que sou um ateu "científico". Vou ler mais e disseminar suas idéias entre os jovens em minha cidade e região.

Cumprimentos!

João Carmo
joaocarmo@terra.com.br

By João Carmo (not verified) on 18 Sep 2005 #permalink

Just wanted to translate what Joao Carmo wrote:

Truly I am fascinated by its book "Evolution, the triumph of an idea", that I finished to read. Congratulations! I age an atheist "politician", now can say that I am "a scientific" atheist. I go to read more and to spread its ideas between the young in my city and region.

Compliments!

--

My own response:

I demasiado, am fascinado pela evolução. Entretanto, eu acredito que o relacionamento entre a teoria evolucionária e a religião é complicado. Para o exemplo, muita daqueles que são tomada religiosa um a leitura mais allegorical do genesis, em que se compreende não como um treatise científico, mas como falando diretamente à alma no formulário da poesia sobre as verdades fundamentais a respeito do relacionamento entre o deus e homem. Este não é algo que você naturalmente tem que em toda a maneira aceitar. Mas o que é importante é que, não obstante que diferenças exista entre opiniões religiosas do pessoa, aquelas vistas religiosas podem ser reservadas ao incorporar o esforço cooperativo sabido como a ciência empírica, onde a evidência (melhor que a fé religiosa) são o que importa verdadeiramente!

Os mais melhores desejos, meu amigo!

--

And the original english:

I too, am fascinated by evolution. However, I believe the relationship between evolutionary theory and religion is a complicated one. For example, many of those who are religious take a more allegorical reading of Genesis, in which it is understood not as a scientific treatise, but as speaking directly to the soul in the form of poetry about fundamental truths regarding the relationship between God and man. This is not something which you of course have to in any way accept. But what is important is that, regardless of what differences exist between people's religious views, those religious views may be set aside when entering the cooperative endeavor known as empirical science, where evidence (rather than religious faith) is what truly matters!

Best wishes, my friend!

By Timothy Chase (not verified) on 18 Sep 2005 #permalink

No doubt some things were "Lost in Translation."

In any case, it should be possible to respect one another's religious beliefs, yet preserve the separation between religion and science which makes scientific progress possible.

For one possible view, people might be interested in the article which formed the basis for a discussion at:

"Religion and Science"
http://www.evcforum.net/cgi-bin/dm.cgi?action=msg&f=32&t=4&m=1

By Timothy Chase (not verified) on 18 Sep 2005 #permalink

I think I'm going to look into that palaeoanthropological publication.

Ah, here we go. "Modern Sci-Ants". Illuminating.

There was this ant, going along the track, and he fell into a sort of a cross-ditch. Then he got out, and then he fell into another one! This kept happenning. A-bye-and-bye, he observed a regularity and a similarity in these trenches. He furthermore observed that although they were in many ways similar - he fell into all of them with a sort of a crash - they were all a little different. A-bye-and-bye, he observed that they differed according to the environment in which they occurred. Some were steeper-sided than others, depending on soil-type, and some were rougher to fall into than others. Bye-and-bye he advanced a theory about these very obvious, similar, yet differing, features of his world. Having observed that the ones he first fell into were a little shallower than many of those he subsequently encountered (the ground was harder back there)he formulated a theory that they were in some way ancestral to those that followed. This ingenious ant postulated some sort of harmonic effect,involving the aethereal aether, coupled with the effect of various debris randomly striking the ground. It actually went some of the way towards providing a theoretical engine to drive this observed progression in well-formed trenches. In time, our hero formulated his ideas into a comprehensive thesis, which said thesis became commonly read and discussed at many learned gatherings. It gained popularity, although some ants were antagonistic. (Sorry!)

The 'dozer driver reversed, and squashed the poor guy.

So how do I know this happened?
I was told it by this ant's aunt. She is eloquant. Or was it the aunt's ant? The ant's aunt undoubtedly elucidated elegantly the extinct ant's anthropology. Or was it that the aunt's ant's absentminded excursion led to the extinct ant's undoing? Ah, now I remember. The absentminded ant's aunt undoubtedly advized me with admirable elocution.
That sci-antist sure thought he had all the antswers!
But did he have a full grasp of palaeoANThropology (sorry, again)!

Hey, this gets better. The next issue is headed, "Was Darwin Jack the Ripper?" Dashed interesting. Yes, certainly they should dig up Westminster Abbey to find if it's really him buried there! It's quite obvious his death was faked, and he went on stangling pigeons and feverishly dissecting specimens in an uncontrolled way in the dead of night, long after this transparent fake of a funeral. OOH, it's creepy! Aaaah! I must go. Palaeoanthropology is so exciting. It's wild, all right.

My compliments to Carl Zimmer.

While of course I was well-aware of the origins of mitochondria and chloroplasts, I did not know that a single-stranded DNA bacteriophage was involved. Reminds me of the single-celled eukaryote employed in termite digestion, which itself plays host to bacteria which are responsible for its mobility (the bacteria row together in synchronicity). In any case, I have brought up both mitochondria and chloroplasts with a number of my friends, and this will give one more interesting detail to the story I tell.

Additionally, I really enjoy your writing. Beyond all of the details (and there are plenty of them), there is something about the style which is really smooth -- the reader doesn't in any sense get the feeling that he is being talked down to (which seems somewhat common in much of science writing), and it has more of the feel of listening to a friend. I find that impressive. Judging from the stories you have written, your book will be very enlightening, but judging from how they are written, it should be a most enjoyable read.

(Still might like to see a story on retroviruses, though -- there is a great deal of potential material in that topic.)

By Timothy Chase (not verified) on 19 Sep 2005 #permalink

I realize this argument has petered out, but I just can't resist pointing out that I'm descended from my Grandmother, and yet, I don't expect I'll be giving birth to her any time soon.

:)

Nitpick: It is Uppsala (up-saa-la) University.

Phillip: A simple experiment would show that the tracks are not antsy but stillborn. Posterior creationist theories has no scientific value; they must be ant-erior to facts.

By Torbjorn Larsson (not verified) on 10 Oct 2005 #permalink

Great article. I have heard this chimera theory before. For all the ID activists; maybe this article will change your mind.