Some notes on the Atlantic cod genome, and fish genomes in general

Teleost fish genome sequences have been absolutely essential to our understanding of vertebrate genome evolution, and to vertebrate evolution in general. Last month I welcomed the addition of the Atlantic cod genome to the sequenced fish genomes, and highlighted some of the main findings of the first analysis of the whole genome sequence. The preliminary genome database is now available for browsing at the Pre!Ensembl database.

After I had written that post, I had some notes left over because I didn't want to make my text too long. But I think they're interesting enough for me to revisit the cod genome and write a new post.


The Atlantic cod, Gadus morhua

The Atlantic cod genome is available

Great news for those of us who are interested in comparative genomics, and fish genomes in particular - yesterday the Atlantic cod genome was made public at the cod genome project website to coincide with the description of the genome, published online in advance by Nature (reference below).

I've been pottering about in the genome since yesterday morning, looking for the gene families I'm researching in my own work, but the database is still quite rudimentary and tricky to use. Most of the sequences I've searched for come back in fragments, and since the genome hasn't been mapped to chromosomes in the database, it's difficult to find out where in the genome individual sequences are, and to "get to know the neighborhood" of the sequence you're interested in, which is essential for comparative genomics. Thankfully it will (probably) get a more user-friendly interface soon, when it becomes integrated with the Ensembl genome browser, where the other five sequenced fish genomes are already available.

I also made this illustration for my collection of genome species.


The Atlantic cod, Gadus morhua

The basic genome stats reveal a pretty standard vertebrate genome, if there is such a thing. The total (haploid) size is estimated at approx. 830 million base pairs, a bit lower than previous estimates, and the number of identified genes is 22,154 (20,095 protein coding). The closest related fish species with a sequenced genome is the three-spined stickleback, Gasterosteus aculeatus, with a genome of approx. 446 million base pairs and 20,787 identified genes. The best studied fish genome, that of the zebrafish Danio rerio is quite a bit longer, with about 1.5 billion base pairs, but the gene content is similar with about 26,000 identified genes.

Quote: Walter Gilbert predicting personal genomics

I'm catching up on my reading this weekend. Right now I'm getting through Misha Angrist's "Here Is A Human Being" and getting increasingly jealous for every page. Angrist had his genome sequenced as a part of the Personal Genome Project, something I wouldn't mind having done myself.

I found this lovely 1992 quote from Walter Gilbert in the book. The number of bases of the human genome was pretty accurate even back in the early nineties.

Three billion bases of DNA sequence can be put on a single compact disc and one will be able to pull a CD out of one's pocket and say, "Here is a human being; it's me!"

This year marks the first decade since the "full" (more or less) sequence of the human genome was announced. But the advancements (and nightmarish visions) many expected still form an alluring horizon. One day, I want to be able to get my genome sequence out and say "Here I am; it's me!" Some people see all kinds of problems with personal genomics, but I can hardly wait for the day.

Still not "new" or "artificial"

After having headed the efforts to transplant a bacterial genome from one species to the other and to create a synthetic bacterial genome from scratch, Craig Venter predicts to finally have a synthetic species created before the end of the year. Judging by the results published in advance on the Science express website last week (find it on the print issue of Science soon), it seems his J. Craig Venter Institute (JCVI) is well on its way.

In a post from last year I commented on the JCVI's creation of a synthetic Mycoplasma genitalium genome and lamented the media coverage's choice of terms ("playing god", "man-made life", "creating life from scratch", et c.) to describe the in and of themselves impressive results. I wrote:

... terms like "playing god" or "creating new life from scratch" are inaccurate because technically you'd have to insert the artificial genome into a host cell and produce a viable organism, one that could replicate itself, before you'd have created life. Theoretically this isn't impossible or even particularly incredible, but it poses a whole lot of technical demands. And would this life actually really be "new" or even entirely synthetic?

With these latest results it seems we're a step closer to just that, even if it still doesn't fulfill the criteria I'd use to characterize a completely new or artificial or even synthetic organism.

By cloning a transformed version of a Mycoplasma mycoides genome in yeast cells, then transplanting it into a recipient cell of a closely relates species, Mycoplasma capricolum, and producing viable colonies of engineered M. mycoides, basically "re-booting" cells with a new genome (how cool is that!?), the team at JCVI developed a protocol through which it would be possible to take a completely synthetic genome, clone it and introduce it into "empty" receptor cells to produce a "new" and engineered species.

The difficulty had been to successfully transplant the engineered bacterial genome from the yeast cells to the final receptor bacterial cell. The use of yeast cells to engineer the genome is essential since there are well-established genetic tools for yeast that are not available for the bacteria used. To solve this issue the team destroyed the recipient cell's defense against foreign DNA, a restriction endonuclease that cleaves foreign DNA into pieces, and modified the donor genome so that it exhibited the same methylation pattern as native M. capricolum DNA. Methylation is a secondary modification of the DNA molecule that affects gene expression and is used by bacterial cells to prevent their own DNA from being cleaved by endonucleases.

It's going to be very interesting to see if JCVI will be able to combine their ability to synthesize a bacterial genome with these latest achievements to create a synthetic species before year's end. Whenever they do it, the question still remains if this would constitute "new" or "artificial" life. In my opinion it would still very much be "old life" put together in new ways, which is still a great feat and an important advance in science, don't get me wrong; but "new life" or "artificial life" are nothing by hype-y buzzwords. I've written two posts about it.

The media reports this time around have so far been better than last year, without hyperbolic mentions of "playing god" or anything like that. There's the article I link to at the top of this post from The Times Online, and another at MIT's Technology Review. Meanwhile a post at a Discover Magazine blog opens with:

Although scientists may not have come close to cataloging all the different kinds of life on the planet, genetics pioneer Craig Venter is pressing ahead with his plans to create biology version 2.0.

Biology version 2.0!? That makes no sense whatsoever.

Lartigue, C., Vashee, S., Algire, M., Chuang, R., Benders, G., Ma, L., Noskov, V., Denisova, E., Gibson, D., Assad-Garcia, N., Alperovich, N., Thomas, D., Merryman, C., Hutchison, C., Smith, H., Venter, J., & Glass, J. (2009). Creating Bacterial Strains from Genomes That Have Been Cloned and Engineered in Yeast Science DOI: 10.1126/science.1173759

Swedish blog tags: Vetenskap, Biologi
Technorati tags: Science, Biology, Genomics, Venter

The new naturalists?

Some time ago I watched a documentary called Lord of the Ants (clips available online) about the brilliant Ed O. Wilson, a born Naturalist whom I've also had the pleasure of hearing in person, and I was struck by his enthusiasm for natural history and the traditional exploratory naturalist work. It fed my imagination and made me think about my own work as a biologist. I'm probably as far away as you can come from a field biologist, working as I do with online genome databases and DNA sequences, but I realized that maybe we still have a lot in common. After watching the documentary I reached for my ever present pad of post-it notes and jolted down "a naturalist in the new world of genomes?"

Note my amusement when I'm scanning through the latest issue of Bioessays and find the following passage in a commentary about recent findings in the field of transposable elements and conserved noncoding sequences (reference below).

Charles Darwin and Alfred Russel Wallace were naturalists. They observed diverse landscapes, noted heritable variations within species, and suggested that challenges and opportunities in the environment would favor the fittest variants. Wallace and Darwin did not, however, understand the source of the variations in morphology that they observed. Evolutionary theory grew out of attention to this variation, but early discussions of evolution generally referred only in passing to the mechanisms that generate variation (as random mutation), and instead focused on selection and drift.

It was not until the discovery of the structure of DNA, about a century after Darwin's Origin of Species was published, that the biochemistry of genetic variation could begin to be understood. However, over the course of the past decade, as genome sequences began to fill the literature, even the most molecular and computational of biologists have become like naturalists. They wander through diverse landscapes of As, Ts, Gs, and Cs, comparing genomes and wonder about the origin of the distinct classes of variation found there.

That's exactly right. For everyone that has spent some time wading through what seems to be never ending stretches of genetic code from several different species, prodding and probing here and there as you go, lifting up interesting or colorful stretches of DNA sequence, looking for new exciting genes perhaps or just trying to make sense of how it all comes together and how it all relates, the likeness to an ecological system is striking. It does require a measure of curiosity and an exploratory vein.

It's probably one of the most accurate descriptions of the kind of work that we do, and one that's easy to subscribe to.

Caporale, L. (2009). Putting together the pieces: evolutionary mechanisms at work within genomes BioEssays, 31 (7), 700-702 DOI: 10.1002/bies.200900067

Swedish blog tags: Biologi, E.O. Wilson
Technorati tags: Genomics, Biology, E.O. Wilson

Sunday science sum-up: More Darwiniana, the neanderthal genome sequence

In response to the fact that I have less time than I would like to sit down and write longer in-depth entries, I thought I'd try posting shorter commentaries on a semi-regular basis.

This week has of course been dominated by Darwin Day, and I would like to amend the list of recommendations in my previous post with a few more entries:

- Leave it to Carl Zimmer to write the most informative and enjoyable summary of Darwin's significance. Most importantly, it addresses what giant leap forward we have taken since - The Ever Evolving Theories of Darwin.

It's only fitting to recognize the accomplishments of a great biologist. But there's a risk to all this Darwinmania: some people may come away with a fundamental misunderstanding about the science of evolution. Once Darwin mailed his manuscript of On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life to his publisher, the science of evolution did not grind to a halt. That would be a bit like saying medicine peaked when Louis Pasteur demonstrated that germs cause diseases.

Today biologists are exploring evolution at a level of detail far beyond what Darwin could, and they're discovering that evolution sometimes works in ways the celebrated naturalist never imagined.

- Little known fact is that many biologists, while well-versed in evolutionary theory, actually haven't read the whole volume that set it all in motion. Out of those that have, few have read the whole thing more than once. This feature in the latest issue of Current Biology departs from that - a group of scientists sit down to re-read 'On the Origin of Species' and write down their impressions from their own unique experiences and perspectives - (Re)Reading The Origin.

Another interesting thing that happened this week, on Darwin Day actually, was the announcement of the first rough draft of the neanderthal genome by researchers from the Max Plank Institute for Evolutionary Anthropology. The work was announced by Svante Pääbo in a press conference this past Thursday. You can watch a video here. Several news stories in the latest issue of Science highlight the details and the potential of this work.

I had the opportunity to hear Svante Pääbo talk at the "Building Complex Brains" symposium last June and this is what I wrote regarding the neanderthal genome in a previous post.

Finally, we heard from Svante Pääbo of the Max Planck Institute for Evolutionary Anthrolopogy in Leipzig on the subject of the genomic perspectives on human origins. I've written about his research on the FOXP2 gene before, but this was a more general talk, only using FOXP2 as an example. A lot of it was on the progress of the sequencing of a neanderthal genome, but also of course about how comparative analyses of the human genome and the neanderthal genome will shine a light on a very crucial point of our evolution. Will we be able to identify genes that were important in our evolution? Will we be be able to define what it is that makes us specifically human? It's difficult to pinpoint what makes us "so special" when more and more of those traits we jealously guarded as "ours" appear in traces in other animals - perhaps looking at the genome, rather than looking at our behaviors and abilities, will be the key. But to do so we need to know more about that last step in the road to where we are today.

It's unquestionably a hugely interesting development and the technology advanced in order to make it possible is impressive. The challenges of virtually "reviving" an extinct genome are humbling - first of all you need to identify a fossil in which ancient DNA has been preserved then the small fragment of bone from which the DNA was extracted needed to be positively identified as neanderthal, and even then only approx. 4% of the total DNA in the sample is of interest as extensive contamination from modern human DNA as well the the decay of DNA into small fragments will do their part.

Reactions to this report have been enthusiast but careful, with reason. They don't have the whole genome sequence so far, "only" approx. 60%, and they have only covered these regions 1,2 times on average. Due to degradation and low coverage it's reasonable to expect a lot of corrupted sequences and sequencing errors. Many genome sequences with higher coverage from existing species are quite problematic in this respect, which makes me question the extent of the analysis we will be able to make before a genome sequence with higher coverage is published. Pääbo seems to think that a 15-20-fold coverage will be possible in the future but even now he hints at many very interesting findings, including signs of selective sweeps in humans compared to the neanderthal genome. This means that they have found parts of the genome and maybe analyzed specific genes that have mutated in the modern human lineage and given such advantage that they are now fixed in the entire human population.

So far no actual publication is clearly in sight, although I can detect several hints that the publication is pretty close. I think most of us will wait and see what answers they deliver with a deeper analysis before cheering loudly.

Swedish blog tags: Vetenskap, Biologi, Evolution, Darwin, Människan
Technorati tags: Science, Biology, Evolution, Darwin, Neanderthal, Genome, Genomics

Nobel season '08: Physiology or Medicine

The Nobel season is upon us! Starting today with the announcement of the physiology or medicine laureates. This year's prize goes to Françoise Barré-Sinoussi and Luc Montagnier for the discovery of the human immunodeficiency virus HIV, and to Harald zur Hausen for the discovery of the human papilloma virus HPV causing cervical cancer. Today over 30 million people live with AIDS and roughly half a million women battle cervical cancer (of which nearly all cases involve HPV infection). Rarely has a Nobel prize winning discovery directly affected the lives of so many and addressed such a current problem.

Their social impact aside, these discoveries were decisive in our understanding of the complex molecular interactions between viruses and their hosts, of the causative agency of viruses in human disease, of how viral diseases spread and of their ecology and evolution. Even of how our genomes work: The replication of both HPV and HIV involves complex genomic interaction between the virus genomes and the host genomes.

HIV replicates by inserting its genome into the genomes of lymphocytes and "fooling" the cell's own molecular factory to produce more virus particles, to the ultimate bane of the host cell. HPV is a different kind of virus, but one of the major discoveries made by zur Hausen is that parts of the HPV DNA does become integrated in the host genome and is expressed in the cervical tumors. So further insight into the complex genomic mechanisms that are behind HIV replication and HPV pathogenesis will undoubtedly help reduce the fatalities from the AIDS pandemic and from cervical cancer, but it will also let us know a bit more about what it is genomes are capable of doing.

Very worthy recipients in a very interesting and relevant field.

Here's a more detailed summary from the advanced information published on the Nobel website.

Professor Harald zur Hausen, emeritus Scientific Director and Chairman of the Management Board of the German Cancer Research Center in Heidelberg, has made seminal observations that identify novel human papilloma viruses as key contributors to cervical cancer. Cervical cancer is the second most common cancer among women. Professor zur Hausen's discoveries include detection of novel human papilloma virus types, isolation of the human papilloma virus types 16 and 18 genomes, and expression of specific papilloma virus DNA genes integrated into the tumour host cell genome. These findings have led to an understanding of cervical carcinogenesis, a characterization of the natural history of the human papilloma virus infection, and paved the way for the development of preventive vaccines.

Professor Francoise Barré-Sinoussi, director of the "Regulation of Retroviral Infections" Unit, Virology department at the Institut Pasteur, Paris, and Professor Luc Montagnier, President of the World Foundation for Aids Research and Prevention, Paris, discovered human immunodeficiency virus-1 (HIV-1), the first human lentivirus. They characterized the virus based on its morphological, biochemical and immunological properties and demonstrated the capacity to induce massive virus replication and cell damage to lymphocytes. The initial discovery of Barré-Sinoussi and Montagnier was a basis for subsequent identification of this virus as the aetiological agent of acquired human immunodeficiency syndrome (AIDS). The discovery has led to epidemiologic surveys, tracing of the origin of HIV-1, identification of novel steps in the retroviral replicative cycle and generation of therapeutic as well as prophylactic options.

Swedish blog tags: Vetenskap, Biologi, Nobel, Nobelpris, HIV, HPV
Technorati tags: Science, Biology, Nobel prize, Medicine, HIV, HPV

Genome Biology on race

The concept of race is something that's often held against biology and evolutionary biology in particular. Genuine concerns based on the use of science (or pseudoscience) in the past to promote racism are mixed with misinterpretations of evolutionary theory to produce a divide between the public and scientific conceptions of race. Deluded creationists and opponents of evolution in particular like to play up and expand this divide by claiming that modern evolutionary theory negates the idea that all humans have equal worth; promoting the ridiculous misconception that evolution reduces us to simple pawns in the "survival of the fittest" and therefore justifies racism, discrimination and genocide.

It's welcome then that multidisciplinary group of scientists from Stanford University has put together an open letter in the latest issue of Genome Biology posing 10 statements that very clearly lay down what's what when discussing race in terms of biology, evolution, genetics, medical research and science in general. It's really worth reading all of it, but there are some points worth highlighting:

We believe that there is no scientific basis for any claim that the pattern of human genetic variation supports hierarchically organized categories of race and ethnicity.

We recognize that individuals of two different geographically defined human populations are more likely to differ at any given site in the genome than are two individuals of the same geographically defined population.

We recognize that racial and ethnic categories are created and maintained within sociopolitical contexts and have shifted in meaning over time.

We caution against making the naive leap to a genetic explanation for group differences in complex traits, especially for human behavioral traits such as IQ scores, tendency towards violence, and degree of athleticism.

If we only could get this through to some thick skulls out there, we'd all be better off.

Lee, S., Mountain, J., Koenig, B., Altman, R., Brown, M., Camarillo, A., Cavalli-Sforza, L., Cho, M., Eberhardt, J., Feldman, M., Ford, R., Greely, H., King, R., Markus, H., Satz, D., Snipp, M., Steele, C., Underhill, P. (2008). The ethics of characterizing difference: guiding principles on using racial categories in human genetics. Genome Biology, 9(7), 404. DOI: 10.1186/gb-2008-9-7-404

Swedish blog tags: Vetenskap, Biologi, Racism
Technorati tags: Science, Biology, Race, Racism

More platypus

I've been poking about a little bit extra in the platypus genome for a week now in response to the platypus genome release article I wrote about in my previous post. It was a pleasant surprise to notice that so many of the gene families we are interested in in our lab have distinguishing features in the platypus. It has the neuropeptide Y7 receptor, which is absent from other mammals; it has a unique galanin receptor that I've been looking into some more; it has the shortwave-sensitive-2 opsin gene, the visual pigment that detects blue light, which is absent in other mammals (we have modified the ultraviolet-light-detecting opsin to see blue light instead)... it's pretty interesting stuff.

I missed this BBC article last week. It's not spectacular, but it has a nice audio interview with professor Jenny Graves at Australian National University, co-author of the genome release paper. I liked this highlight of what we are able to learn about evolutionary transitions by looking into and comparing genomes:

The platypus is a mammal, it makes milk and it has fur so it is defined as a mammal, but it left the rest of the mammals a long time ago. It diverged 166 million years ago from a common ancestor that probably looked more like a reptile than a mammal. So it's not a reptile, it is a mammal but it's retained a lot of reptilian characteristics like laying eggs for instance... Of course one of the things we wanted to look at was egg-laying and making milk because we want to retrace the steps in how did we get to be mammals? and so first of all we looked at the egg yolk proteins and indeed there is an egg yolk protein there, but there's only one of them whereas birds have three for instance. So it looks as though the platypus is already shifting its allegiance from nurturing their young inside an egg and nurturing their young with milk.

There have also been quite a few blog posts concerning the platypus, which is fun. Pharyngula and Adaptive Complexity both have very comprehensive posts and both also take issue with the purported image of the platypus as a composite creature, "part bird, part reptile, part mammal"; Genomicron and Nimravid focus on the problem with calling the platypus "primitive" or defining its characteristics as "reptilian" or "avian"; Carl Zimmer just wants to know where the platypus' stomach went and The Digital Cuttlefish shares with us a few inspired words.

Swedish blog tags: Vetenskap, Biologi
Technorati tags: Science, Biology, Genomics, Platypus

Ph34r the platypus!

Proof that god has a sense of humor? Or simply an amazing creature whose unique combination of features are the result of an intriguing evolutionary history? You guessed it.

Not that we needed another reason to love the platypus - looking something like the cross between a beaver and a duck, being venomous, endemic to Australia and one of the two mammals that lay eggs is awesome enough - but now that we have its genome sequence (the release-paper having been published yesterday in Nature) we have the chance to learn a lot about how modern mammals evolved from more reptile-like beginnings.

The New York Times writes:

If it has a bill and webbed feet like a duck, lays eggs like a bird or a reptile but also produces milk and has a coat of fur like a mammal, what could the genetics of the duck-billed platypus possibly be like? Well, just as peculiar: an amalgam of genes reflecting significant branching and transitions in evolution.

In short, there are elements and patterns in the genome that are very similar to those in birds and reptiles and others that are decidedly mammal.

Several "reptilian" genes involved in vision, circadian rhythm and food intake are present in the platypus but have been lost other mammals, while of course the genes for the milk proteins caseins and their arrangement are as mammal as can be. Some of the genes for the proteins that coat the egg-cell before fertilization are shared with other mammals while others have only previously been found in fish, amphibians and birds - just to give some examples.

But even though its apparent mix of features is reflected in its genome, the platypus is not "part bird, part reptile, part mammal" like some popular science outlets sloppily have written. Science Daily and New Scientist really should know better. The platypus is a representative of a group of mammals that diverged from the rest of the mammal lineage at an important transition from more reptile-like creatures towards modern mammals. By comparing, for instance, our genome with the platypus genome we get an insight into how that transition took place. That's precisely why it's a beautiful addition in our understanding of how evolution has put genomes together. Not because it's a "lizard-bird-mammal" in any sort of way.

There are also some pretty cool unique features to the platypus genome. It has a lot of genes for odorant receptors that cannot be found in other animals - possibly to detect water soluble odorants when it forages underwater, or maybe as part of a highly advanced pheromonal system? I mentioned in the beginning that platypuses were venomous (the males inject the venom through a spur on their hind legs) - it turns out that the proteins that make up the platypus venom are not a "reptilian" character but have evolved independently in reptiles and in the platypus.

I have been using the preliminary platypus genome sequence in my research for a while now, trying to figure out how the genes that make up part of the brain's endocrine systems have evolved. It's been a nice addition to my evolutionary trees and I count on it to continue to be very useful in the future.

>> Edited May 16, 2008.

Warren, W.C. et. al. (2008). Genome analysis of the platypus reveals unique signatures of evolution. Nature, 453(7192), 175-183. DOI: 10.1038/nature06936

Swedish blog tags: Vetenskap, Biologi
Technorati tags: Science, Biology, Genomics, Platypus

"New life" pt. 2 and the minimal genome

In my last post I discussed why "new" or "man-made" life wouldn't really be all that new and I ended with the suggestion that the road towards making "new" synthetic life might be a goal all in itself. I would like to elaborate a little bit on that and then write something about why Mycoplasma genitalium is so interesting in this respect.

The end of creating "synthetic organisms" (a term used loosely) would be something like "engineered" bacteria that would produce specific substances or maybe even catalyze particularly interesting biochemical reactions. This is not that different from what we're already capable of doing, granted it would be in a larger scale. Putting synthesized DNA, especially designed for a purpose, into living cells and having them express that DNA is common practice in molecular biology, even though it has its limitations. You can buy the cells from catalogs and the whole process is carried out with ready-made kits by just following the instructions in the box.

The strength of producing "synthetic organisms" would be that you could create entire systems and not just get the bacterium to produce one or a few substances. You could design the biochemical cellular environment of that organism on a larger scale and gear it towards one preset goal. This is because theoretically you could control every aspect of that organism's genome: not only everything that the cell produces but also how it regulates itself. But the key thing to look out for here is "every aspect". We are still far away from having a complete understanding of how genomes are made up. So a scenario where we have absolute control of an organism's biochemical processes seems far ahead in the future - another reason why the headlines of "new" or "man-made" life are exaggerations - but getting there we will undoubtedly have to learn more about how evolution has built genomes and what exactly is needed to constitute a functioning genome. A very exciting prospect.

It's in this regard that Mycoplasma genitalium is important. It has the smallest known genome of any self-replicating organism and it's one of the simplest free-living bacteria there are. It only has 482 protein-coding genes, compared to us humans' approx. 20,000 (at the last count). In 1995 it became the second genome to be sequenced for this reason and no doubt this is what makes it such a good candidate to be the stepping stone towards the creation of a "synthetic" organism. By looking at Mycoplasma we can deduce what the minimal requirements are for a genome to work: how many genes are necessary for sustaining life?

At the last count in Mycoplasma genitalium from 2006, 387 out of 482 protein-coding genes and 43 structural RNA genes are essential for the growth of this bacterium. This was deduced by mutating gene after gene, making them useless one after the other, and seeing whether or not the mutant bacteria could live and grow. The real interesting number though, is 110. 110 of the 387 essential genes still have unknown function. The genes have been identified in the DNA, but it's still unknown what they do or what hypothetical proteins are produced from them.

So we're not yet in a time where we know every aspect of what an organism does, not even one of the simplest ones, and we're not yet in a time where we can design an entire viable genome in our interest and thus control every aspect of an organisms biochemical processes, or in other words, "play god".

If or when that day comes, there's no doubt that many exciting and useful applications will be available to us. But let's not forget that during the process we will have acquired a wealth of knowledge about ourselves and indeed life itself that will be difficult to overestimate. Then the answer to the question whether or not we should "create life" (again, using the term very loosely) just because we can, gains a whole new dimension.

Glass, J.I. (2006). Essential genes of a minimal bacterium. Proceedings of the National Academy of Sciences, 103(2), 425-430. DOI: 10.1073/pnas.0510013103

Gibson, D.G., Benders, G.A., Andrews-Pfannkoch, C., Denisova, E.A., Baden-Tillson, H., Zaveri, J., Stockwell, T.B., Brownley, A., Thomas, D.W., Algire, M.A., Merryman, C., Young, L., Noskov, V.N., Glass, J.I., Venter, J.C., Hutchison, C.A., Smith, H.O. (2008). Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science DOI: 10.1126/science.1151721

Swedish blog tags: Vetenskap, Biologi
Technorati tags: Science, Biology, Genomics, Venter

"New life"

There's been a lot of interest in the media concerning the results published by the J. Craig Venter institute last week in Science - the synthesis of a completely artificial genome, or rather, the synthesis of a down-sized replica of the genome of the bacterium Mycoplasma genitalium.

The words "playing god", "man-made life" and "building new life from scratch" have been thrown around, unfortunately; not only because it makes synthetic biology more controversial than it needs to be, but because in essence they're wrong. Carl Zimmer has written two excellent pieces explaining the actual achievement and clearing out the misconceptions; but in short, terms like "playing god" or "creating new life from scratch" are inaccurate because technically you'd have to insert the artificial genome into a host cell and produce a viable organism, one that could replicate itself, before you'd have created life. Theoretically this isn't impossible or even particularly incredible, but it poses a whole lot of technical demands. And would this life actually really be "new" or even entirely synthetic?

Aside from this, actual living organisms, "old life", are still required to carry out the essential parts of the process for us. Both E. coli bacteria and baker's yeast, Saccharomyces cerevisiae, common biological model organisms, were required in this case. They're like little biochemical factories doing the job for us, putting the artificially synthesized blocks of DNA together to form the genome, basically a bigger ring-shaped DNA molecule. It's still largely unknown how they do it.

I'd also put the extra demand that this new organism would have to "do" something new in order to be called a true new organism. Its genome would have to be engineered in a way that allowed it to do something that no other living organism before it has done. Something like producing new "engineered" gene products or catalyzing new and exciting biochemical reactions. That would be seriously awesome. The J. Craig Venter institute speculates:

Scientists foresee many potential positive applications including new pharmaceuticals, biologically produced (“green”) fuels, and the possibility of rapidly generating vaccines against emerging microbial diseases.

So all in all it seems we are quite a bit away from "playing god". Not even when an artificial genome has been introduced into a host cell, creating a viable "new" organism, will we be even close to knowing how evolution has built genomes and how all of its parts interact to produce life. We're not making life, we're cheating by using bits and pieces of "old" life and putting it together in "new" ways. Carl Zimmer writes:

When and if Venter’s team does create a viable synthetic life form, our ignorance will still remain profound. <...> Scientists have gotten very good at manipulating genes--at copying them or using them to make biotechnology products like insulin--but they still know relatively little about how genes work together in living things.

Who knows if we will ever be able to create something entirely new. But the journey there seems like a pretty decent goal all in itself.

Gibson, D.G., Benders, G.A., Andrews-Pfannkoch, C., Denisova, E.A., Baden-Tillson, H., Zaveri, J., Stockwell, T.B., Brownley, A., Thomas, D.W., Algire, M.A., Merryman, C., Young, L., Noskov, V.N., Glass, J.I., Venter, J.C., Hutchison, C.A., Smith, H.O. (2008). Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science DOI: 10.1126/science.1151721

Swedish blog tags: Vetenskap, Biologi
Technorati tags: Science, Biology, Genomics, Venter