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Friday, 7 November 2008

Viruses-the power of DNA

A very detailed article on the amazing life of viruses.
I loved most the phrase "But in truth we're all leaky vessels, and DNA knows no bounds.". It definitely make you think what exactly we are. We're not a body, because we're more than that. But we're also a body. A body that has so complex and profound history. It's very very interesting thing to ponder on.
And if you close your eyes and look carefully inside your body, you almost can hear the voice of your ancestors and all the other people-their hopes, their dreams, their emotions-all of that, encoded on a piece of genome attached to your cells. It's so personal and in the same time-impersonal. You have a part of all those people and creatures that lived on our planet, and in the same time, it's not them. It's just a piece of machinery, a piece of matter. A matter that we are not. And in the same time, we are.
After reading this, how could you consider animals less than us, when we share so much with them. How could you regard your fellow humans as enemies when you cannot tell the boundary between you and them.
Understanding Nature is really a spiritual experience.

Viruses: The unsung heroes of evolution


27 August 2008
NewScientist.com news service
Garry Hamilton

Since the discovery of DNA, biologists have insisted they have the answer: complexity arises as the result of small errors that occur when genomes are copied and passed down the generations. Although individually small, these mutations can add up to enormous change across the vastness of time.

This view of evolution has held sway for about 50 years, but now biologists are sensing that it is missing a major element - viruses. For close to a century, these genetic parasites have been regarded as little more than a biological afterthought, notable mainly for their ability to cause death and disease. However, the era of genomics has unexpectedly revealed a much richer picture of viruses as a creative evolutionary force of unparalleled reach and power. "Everywhere you look, viruses seem to be playing a crucial role in evolution," says Luis Villarreal, director of the Center for Virus Research at the University of California, Irvine. "I would argue that they are the most creative genetic entities that we know of."

Viruses by definition are parasites, utterly dependent on their hosts for survival, and viral infections have been responsible for some of the worst epidemics in human history.

In the late 1980s, however, this view began to change. Researchers started exploring the size and diversity of the viral world, or "virosphere", by taking samples from different environments and counting the viruses. A millilitre of water from the Barents Sea turned out to contain 60,000 virus particles, and a similar sample from Lake Plussee in Germany contained 254 million. These and other results suggested viruses were up to 10 million times more common than previously estimated.

Subsequent research has confirmed that viruses are everywhere, in great abundance. They are found in hot springs, deserts, polar lakes and rocks 2000 metres below ground - anywhere there are life forms to infect. "There are more bacteriophages [viruses that infect bacteria] in the biosphere than all other life forms added together," says Graham Hatfull of the University of Pittsburgh in Pennsylvania."The world is mostly viral. They are the most abundant and diverse genetic entities."

This diversity in the virosphere is also coming as a surprise. There are now thought to be around 100 million types of virus. They boast a more varied biochemistry than cellular life, storing their genetic information as both single and double-stranded DNA and RNA. Recent virus-hunting expeditions have uncovered one with a unique hybrid genome structure, part single-stranded and part double-stranded DNA, plus a menagerie of novel forms - bottle-shaped viruses, viruses with tails at both ends, viruses shaped like droplets and viruses that resemble stalk-like filaments. Most astonishing of all is the giant mimivirus , which is bigger than some bacteria (New Scientist, 25 March 2006, p 37). And we have only scratched the surface. "In terms of diversity, I don't think we even have an inkling yet what's out there," says Curtis Suttle, a microbiologist at the University of British Columbia in Vancouver, Canada.

Perhaps most surprising of all, the more virus genomes we comb through, the more we are discovering hundreds of genes never seen anywhere else - not in any other virus, nor any living cell. According to Villarreal, these make up an amazing 80 per cent of viral genes, yet their function remains a mystery.

Such diversity comes as a surprise partly because viruses have long been considered cast-offs from the tree of life - shards of non-living genetic material that somehow escaped from cellular life forms and became parasites. As the number of sequenced viral genomes climbs towards 1000, however, there is a growing belief that viruses have a more interesting story to tell. "Most virologists no longer believe that viruses derived from host genome sequences, but instead that they arose as independent life forms, probably prior to bacteria," says science writer Frank Ryan, author of Virus X: Tracking the new killer plagues.

One important piece of the story emerged when Hatfull and his colleague Roger Hendrix compared the genomes of dozens of bacteriophages to map their evolutionary history. They found that instead of assorting into a family tree based on common ancestry, each phage appears to be a patchwork of randomly assembled fragments of DNA. Their conclusion was that viruses are genetic grab-bags whose genomes are constantly being mashed up with DNA from other viruses infecting the same host.

This genetic pick 'n' mix is no localised affair. Identical viral genes have been found in vastly different habitats on opposite sides of the world, suggesting that sequences are constantly being copied and pasted from virus to virus around a global DNA superhighway. "Viral genetic information is essentially being distributed all around the planet, presumably by different viruses recombining when they infect the same cells," says Shuttle. Add in a rapid mutation rate, and viruses quickly emerge as life's most fertile breeding ground for novel DNA sequences.

It turns out that this genetic productivity isn't confined to the viruses, but reaches deep into the cells of their hosts too. The first hints of this emerged in the 1950s, when researchers discovered that not all phage infections are the same. While many such viruses follow a scorched-earth policy - destroy one cell then move on to the next - others employ a longer-term strategy, inserting themselves into their host's genome and multiplying only when the cell divides. These "prophages" can sometimes re-emerge as virus particles, but they can also bed down as permanent additions to the bacterial DNA.

Such intrusions were considered freak events until recently, when genome sequencing revealed that between 10 and 20 per cent of DNA in most bacteria is prophage. In addition to that is a subset of bacterial genes called ORFans that bear no resemblance to genes seen anywhere else.

"When you sequence a [bacterial] genome, you always end up with genes that are unknown, usually around 10 per cent," says Patrick Forterre at Paris-Sud University in Orsay, France. "Even today, after more than 500 genomes, whenever you sequence a new one you still get 10 per cent ORFans." Forterre has found that ORFans tend to be small, much like viral genes, and many are located close to a common site of prophage integration. His conclusion is that 90 per cent of ORFans probably have viral origins.

It's not just bacteria that are full of virus genes. Geneticists have discovered that the genomes of every living organism appear to be laden with the remains of ancient viral infections. In eukaryotes, the most complex domain of cellular life including humans, the main source of this DNA is retroviruses - RNA viruses that, after infecting a cell, convert their genome into DNA and integrate it into the host. Sometimes they become a permanent addition, called an endogenous retrovirus, or ERV.

ERVs have been known of since the 1970s, but the full extent of their infiltration did not become apparent until 2003, when genome sequencing revealed that our DNA is absolutely dripping with them. At least 8 per cent of the human genome consists of clearly-identifiable ERVs. Another 40 to 50 per cent looks suspiciously ERV-like, and much of the rest consists of DNA elements that multiply and spread in virus-like ways. Taken together, virus-like genes represent a staggering 90 per cent of the human genome. ERVs have also been found in rodents, apes, monkeys, koalas - essentially everywhere geneticists look. "

The curious thing about all this viral DNA is that it isn't just taking up room - a significant amount of it is functional. "Most [viral genes] don't play a role and they're eliminated," says Forterre. "But from time to time, when a protein does become useful to the cell for whatever reason, it can be retained, and then it can sometimes really change the story of the lineage - it can change the cell's evolutionary direction."

Radical evolution

Prophage genes also turn out to be useful in other settings. For example, Hatfull has identified one that gives bacteria the ability to get together in communal groups called biofilms.
Harald Bressow, a microbiologist at Nestlee? in Lausanne, Switzerland, has suggested that viral DNA provides bacteria with an evolutionary "second gear" that allows them to respond rapidly to short-term environmental pressures by acquiring radical new capabilities.

Evidence is mounting that viruses contribute to the biology of multicellular life forms too, including humans. The most dramatic example is the mammalian placenta, whose evolution is thought to have been pivotal to the rise of modern mammals. One of the key genes involved in placenta formation is called syncytin. In 2000, researchers at the Genetics Institute in Cambridge, Massachusetts, reported that the gene came from an ERV (Nature, vol 403, p 785).

The cytoplasm of human cells is brimming with messenger RNA derived from viral genes, and the European Molecular Biology Laboratory in Heidelberg, Germany, recently published a list of 35 viral genes that appear to play a vital role in human biology. Viruses also appear to have played crucial roles in the evolution of the ability of our immune system to respond rapidly to pathogens it has never encountered before - one of the most important innovations of the past 500 million years. Sequences derived from ERVs also appear to be heavily involved in gene regulatory networks, which control when and where genes are switched on and off. Again, this fingers them as a key driver of evolution: the main difference between closely related species is not in genes themselves but how they are expressed.

Perhaps viruses' most dramatic claim to a starring role in evolution involves events in the dim and distant past. According to Forterre and others, viruses were responsible for some or even all of the main events in early evolution, including the invention of cells.

In the 1970s, Forterre began studying the molecular machinery involved in DNA replication. Scientists had only just learned that cellular life comprises three domains - bacteria, archaea and eukaryotes - and thought that comparing universal biochemical processes such as DNA replication could yield insights into how the domains were related.

But the results were perplexing. While some components showed the expected signs of common ancestry across all domains, others displayed more puzzling relationships. For example, DNA replication enzymes in archaea and eukaryotes are clearly related, but the bacterial versions are totally different. Other components were found to be the same in archaea and bacteria, but different in eukaryotes. This patchwork of shared features means it is impossible to arrange the three domains in a standard family tree.

This suggested to Forterre that the three domains might be the survivors of a much more diverse primordial biosphere that predates the evolution of cells (Proceedings of the National Academy of Sciences, vol 103, p 3669). Forterre and others have since built up evidence that early life was a period of wild biochemical experimentation in which molecular systems were constantly being invented and thrown together into new and increasingly complex ensembles (Virus Research, vol 117, p5). Once cells evolved, the experimentation continued, driven by innovation and gene transfer by the first viruses. The result was the creation of numerous alternative living systems, built up from random combinations of the available components. Only three of these systems survive to this day in the form of the three domains of cellular life; much of the rest lives on in the virosphere.

That puts viruses right at the heart of early evolution. "If you consider that viruses have always been more abundant than cells, you should conclude that the flow of genes has always been higher from viruses to cells," says Forterre.

Forterre now believes that the creative power of viruses lies behind many early leaps in complexity, such as the transition from the RNA world to that of DNA and the invention of the cell nucleus.

All in all, biologists are confronting what may be the biggest advance in evolutionary thinking since the discovery of the gene. Our emerging knowledge of viruses challenges many tenets of evolution, not least that it is driven by competition between selfish genes. Viruses provide a strong argument for the idea that evolution is also driven by fitness boosts gained through give and take.

Nor is evolution necessarily a gradual process. The rate at which viruses shuffle DNA around suggests that life is capable of acquiring fresh new material out of the blue, and also of making dramatic leaps in the time it takes to catch a cold.

Perhaps the most profound change will be in our concept of organisms and species. Individuals are supposed to be distinct packages of genetic information that have been passed along an unbroken line of ancestors extending back millions, if not billions, of years. But in truth we're all leaky vessels, and DNA knows no bounds. Garry Hamilton is a writer in Seattle, Washington

From issue 2671 of New Scientist magazine, 27 August 2008, page 38-41 source

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