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Women in Science: Genome Invaders – Friend or foe?

genome 300x300 Women in Science: Genome Invaders   Friend or foe?

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Ravinder Kanda is a researcher in the Department of Zoology, University of Oxford. Since her PhD at Imperial College in human evolutionary genetics, she has spent time working in industry (paternity testing / forensic science) and as a schoolteacher, but found that she couldn’t stay away from her passion and eventually returned to research science. Her research focuses on the various evolutionary processes that shape genomes, in particular the endogenous retroviruses that infest the genomes of humans and other vertebrates. Ravinder took part in Soapbox Science 2013, on 5th July where she stood on a soapbox on London’s Southbank and spoke to the public about her work and to help promote the role of women in science. www.soapboxscience.org

I remember when I was younger, my mother returning at 1am from a call out (she was a midwife). She had woken me at 11, to let me know she’d been called out. I’d lain awake, drifting in and out of sleep, awaiting her return. She looked exhausted and unhappy when she got back.

I asked her if everything was OK, and she explained to me that the baby she had just delivered was stillborn, as it didn’t have a skull (anencephaly), and couldn’t survive the birthing process—it had come as a huge shock to both her and the mother, as neither was aware there was a problem. She pulled out her textbooks and showed me a picture and we spoke at length about the various disorders that some of the babies that she delivered were born with, mainly genetic. For me, this 1am science lesson, was the spark that ignited my passion for genetics.

Evolutionary genetics is where I found my real interest lay. Less than 2 per cent of our genome is actually coding—and by that I mean the genes that describe your hair colour/eye colour/ height etc. The rest of the genome is a veritable graveyard of “junk”, consisting of old genes that have lost their function, repetitive strings of DNA whose function is not fully understood, and various other recognisable repeat elements. One such element is a virus; to be specific, something we call endogenous retroviruses (ERVs).

ERVs are all descended from viruses, very like those that cause disease today, like HIV, which have managed to insert themselves into our ancestors’ DNA in the distant past, millions of years ago. They are fairly ancient, and over time, have lost their function. But they do make up a significant proportion of the genome—approximately 8% in humans. We are not unique in this respect—ERVs are present in many other species.

You might be asking yourself at this point, why do we bother to look at these bits of DNA that are ancient, with no function—what’s the point? These integrated viruses are the equivalent of fossils in our genome—they provide a record of what has happened in our genome, and looking at these “fossil viruses” allows us to better understand how our genome (or any genome for that matter) has evolved.

The way this particular group of viruses, called retroviruses, infect a cell involves inserting themselves into the DNA of the cell – they become part of our DNA. Once inside the DNA of a cell, new copies of the retrovirus can be produced using the cell’s machinery. These new copies can then leave the cell and go on to infect other cells.

Occasionally, a retrovirus will infect the germ-line cells – the cells that produce sperm and eggs. In this instance, the virus is now part of the DNA of that sperm or egg cell. When fertilisation occurs, this one cell divides to become two. Both cells now contain a copy of the virus. Two cells go on to make four – all have the viral DNA too. When that fertilised egg develops into an adult, every single cell in that individual’s body contains the viral DNA. When this happens this virus is known as an endogenous retrovirus, meaning it is within our genome. It is inherited by all the offspring of that individual.

There are around 100,000 copies of these ERVs in our genome. By comparing the DNA of other primates and mammals, we can estimate how long ago these ERVs inserted into the DNA of our ancestors. For example, it is estimated that the common ancestor of our closest relative, the chimpanzee, and modern day humans existed approximately 8 million years ago. If a particular ERV is present in the DNA of both humans and chimpanzees, we can say that it must have inserted into the DNA of our ancestor more than 8 million years ago.

We can then look at the next closest relative, the gorilla, and see if the ERV is present in their DNA. If it is present in the gorilla, the common ancestor of humans, chimpanzees and gorillas is thought to have existed around 15 million years ago and so we can say that the ERV inserted into the DNA of our ancestors 15 million years ago. Some of the ERV insertions are ancient, dating back 100 million years.

In some instances, we have managed to ‘steal’ some of the viral genes and use them for our benefit. The most famous example is a gene that is involved in pregnancy (syncitin), specifically with the formation of the placenta. This gene comes from a virus and is essential for the formation of the placenta. Without it we would not be able to reproduce as we do.

In other species, there are instances where having a particular ERV gives you some protection against infection from other related retroviruses. For example, sheep have a particular ERV that can block the receptors of a cell, preventing entry into the cell and therefore infection by other related viruses. With the wealth of data emerging from the various genome sequencing projects we hear so much about in the news, numerous examples are emerging whereby a retroviral insertion provides an immunological advantage, in a variety of different species.

For me personally, it is this aspect of ERVs that fascinates me—the role that ERVs play with regards to offering immunity against infection from other viruses. The idea of using viruses against themselves is an intriguing strategy. I use mathematical models to better understand the conditions under which these “genome invaders” might successfully invade and proliferate within our genomes. Perhaps in some instances, this might be the only way in which we can defend ourselves from the onslaught of viral infection… if you can’t beat them, join them!

Many ERVs in our DNA are ancient, indicating that these invasions have been occurring for millions of years. By comparing those viruses that are present in genomes, to viruses that currently infect and cause disease, we can glean clues as to how these viruses might change and evolve. For example, a HIV—like virus has been found in the Madagascan gray mouse lemur genome, which has been isolated for 14 million years, so we know that the HIV family of viruses has been infecting primates for at least that long. The subgroup of viruses to which HIV belongs – lentiviruses – has recently been discovered in the rabbit genome. Which tells us that this is clearly an ancient family of viruses; it’s been around for a long time.

But we also have to consider that if a virus can go into a genome –could it also come out in the same way? The ones we have found in the human genome are all very old and have been inactive for many years, but there are species which do have active ERVs; the virus is incorporating into their genomes today, where this could be a distinct possibility. Mice are known to have many active retroviruses.

A more recent discovery is the Koala RetroVirus (KoRV) that currently plagues the koala population in Australia. Interestingly, this virus also seems to be incorporating into the genome of the koala in the North of Australia, but it hasn’t yet spread through the entire population; there are still some groups of koalas in Southern Australia, that do not yet have the virus in their genome. KoRV is very similar at the DNA level, to another virus that has been identified in the gibbon (Gibbon Ape Leukemia Virus—GaLV), indicating that this particular virus has somehow managed to jump out of the gibbon and into the koala. Emergent infectious disease is a possibility we need to consider.

Some of these viruses are very good at jumping and infecting different species to those in which they were originally found; cross-species transmission, as is the case with KoRV. And we see numerous examples of this phenomenon in many different species. Perhaps one of the best studied examples is the cross-species transmission of HIV from primates to humans. We know that HIV was a virus that originally infected primates. It has been transmitted to humans several times independently, from chimpanzees, gorillas, and lemurs.

All of these discoveries challenge our understanding of how these viruses might change and evolve. However, we need a better understanding of exactly how, where, and why this occurs. Everything we know so far raises more questions: Are some species more susceptible to infection/transmission of these viruses? And if so, are there “hotspots” — perhaps geographical areas where these species exist — where cross-species transmission and subsequent emergent infection may pose more of a risk? Are some viruses better at playing these kinds of games, and if so which ones?

And all that, is what makes these genome invaders so interesting!

There is a noticeable lack of women at the higher levels of science, which is a problem that needs to be addressed. I think I was fortunate that at home I had a strong female role model in my mother, who made no distinction between men and women in ability, aspiration or expectation, and was raised in an enlightened middle-class community where women are expected to follow their ambitions—opportunities that were certainly not available to my mother.

Not everyone is that fortunate though. There are a number of issues that affect the chances for succeeding as a woman, many of which have been highlighted in the various blogs from the speakers at Soapbox Science (see www.soapboxscience.org). Soapbox Science aims to address this problem by helping to improve the visibility of women in science. It was a fantastic opportunity to play a part in something so important. We had an excellent turnout, with people from all walks of life stopping to listen and ask questions. A fun day where I got to stand a soapbox and engage with the public, speaking about something I feel passionate about—my research… what more could a girl ask?

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  • Captain Yossarian

    Very interesting and well-explained, thanks.

  • Christine Ballone

    very important work and i actually understood, thank you!

  • disquschester

    Many thanks. Although I am fairly knowledgeable, this addressed one of the many areas of my ignorance! More please.

  • Hill244

    Height is a variable – poverty equals shortness and is not a genetic factor.

  • disquschester

    Don’t get confused. Poverty can lead to stunted growth, which is not the same thing. My parents were of short stature, so am I. We were all well-fed. The important thing is to ensure that children get good nutrition, so that they can achieve their genetic potential. Your heart is in the right place, just keep learning.

  • Hill244

    Ta!


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