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The human genome 10 years on – so what?
Matthew Cobb   Apr 12, 2010   Why Evolution is True  

The genome has turned out to be a much more complicated place than many people expected. Nevertheless, we are living through an astonishing revolution in science, and young biologists should be grabbing the opportunity to make some amazing discoveries about the evolution of life.


On June 25, 2000, Bill Clinton, flanked by Francis Collins of the National Human Genome Research Institute and Craig Venter of Celera Genomics, with Tony Blair incongruously at the end of a satellite feed, stood at the White House. Clinton announced that “the international Human Genome Project and Celera Genomics Corporation have both completed an initial sequencing of the human genome – the genetic blueprint for human beings.” They claimed that the genome “promises to lead to a new era of molecular medicine, an era that will bring new ways to prevent, diagnose, treat and cure disease”.

In this week’s issue of Nature (which published the draft sequence in February 2001), there is the first of what will undoubtedly be a series of articles and books looking at what has happened over the last 10 years [these articles are open access].

Or maybe there won’t be any such flood of publications, for the simple reason that, despite all the hype, the contribution of the genome to human health has been pretty negligible. In other words, from a purely medical point of view, there isn’t much to celebrate.

Part of the reason for this slight sense of disappointment can be found in that first, triumphal declaration: a genome is not a “blueprint”, in the sense of a plan that can be read off to deduce a particular structure or behaviour. You cannot look at the chicken genome and deduce that a cockerel will go “cock-a-doodle-doo”. And there are no “cancer genes”.

The genome has turned out to be a much more complicated place than many suspected (I would argue that many of us who actually worked on how genes function in whole organisms predicted this). Genes regulate other genes and, above all, interact with the environment. Organisms are not simply the expression of the genome, they are constructed through myriad interactions between the environment and the genes.

And those interactions turn out to be incredibly complicated. Although computing power has also increased over the last 10 years, attempts to model what all these genes are doing have floundered, and people who work in these areas are in danger of drowning in a sea of data. Those who thought there were big bucks to be made have still to make their fortune; many have lost their shirts. My hunch is that it will be a long time before the promised health benefits turn up.

On the other hand, the prospect of lots of money – and health benefits – did mean that a massive amount of attention was paid to sequencing, and the result has been an unprecedented explosion of information about the evolution of life. Over 3,800 organisms (including around 200 humans) have had their entire genomes sequenced, while sequence information on more than 200,000 species has been obtained. This figure is growing all the time, as the price of sequencing plummets and the ease of obtaining entire genomes increases.

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We are living through an astonishing revolution in science, and young biologists should be grabbing the opportunity to make some amazing discoveries about the evolution of life. For example, I am interested in the evolution of the sense of smell. These databases contain the sequences of genes that code for olfactory receptors; it is relatively straightforward to see how they evolved in different lineages, and above all, to gain insight into the role of this sense in the life of a given organism.

Up until 2004, it was argued that birds didn’t have much of a sense of smell (there was no real basis for this prejudice, but it was widely held). Then the chicken genome revealed that there were over 500 olfactory receptor genes (more than in a human). And this week, the genome of the zebra finch reveals that this songbird has about 215 functional olfactory receptor genes. This should be leading people to start finding out what exactly birds are doing with their sense of smell – finding food, navigating, finding mates?

For any young scientists reading this – not just biologists, but computer scientists, mathematicians, chemists – the current revolution in genomics should be seen as a new ocean to explore, a sea of unexploited knowledge that they can play in. It really is that amazing. As the poet William Wordsworth wrote with regard to a rather more bloody revolution – the French revolution of 1789:

“Bliss was it in that dawn to be alive,
But to be young was very heaven!”




COMMENTS

“Complexity is in the eye of the bewildered”. Trajectories of planets looked incredibly complex while assuming that everything rotated around the Earth. PostModern Genomics (called HoloGenomics where Genomics is unified with Epigenomics, expressed in Informatics) is focusing on a “Galilean combination; Simplification, Unification and Mathematization”. One of such novel (2002) concept is “FractoGene” that is “the fractal DNA governs growth of fractal organelles, organs and organisms”. For instance, a Mandelbrot Set looks maddeningly complex as far as visuals are concerned - though it is fully determined by the astonishingly simple equation: Z=Z^2+C (mind you, Z is not an ordinary real value, but a complex number).

Also on a positive note, probably Francis Collins (M.D., Ph.D., Director of the NIH) disagrees that “the contribution of the genome to human health has been pretty negligible”. In his early 2010 book he cites evidence how his lifestyle and wellness program was drastically changed (as well as many other named or pseudonamed individuals’) in view of very partial genome interrogation.

Even more hopefully, just a single letter of A,C,T,G (out of the 6.2 Bn bases) of Sergey Brin already compelled him to both changing his lifestyle to prevention, as well as to mobilize significant amounts of his wealth in order to turn vast amount of knowledge (available) into understanding in terms of informatics (the kind Samsung is aiming for with Korean genomics…)

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