A new announcement from the Human Genome Project

Posted 20 October 2004 by PZ Myers

The human genome project has reached another landmark, the effective completion of the euchromatic sequence. It's still not 100% done, but the remaining small bits are going to require some new tricks to ferret out. You may recall announcements all over the place back in 2001 that the genome had been sequenced, but that was the draft sequence; 90% of the euchromatic genome was done, but there were still about 150,000 gaps scattered through it. You have to think of this project as something like assembling a colossal jigsaw puzzle—when the draft was done, we had a pretty good idea of the structure of the picture, and maybe had the borders done, but there were still these broad patches of solid colors that hadn't been pieced together yet. At this point, though, most of those have been filled in and the gaps are smaller and sparser.

Some numbers: the completed sequence so far consists of 2,851,330,913 nucleotides. There are only 341 gaps left in the sequence. and 33 of those are in the heterochromatin (the mildly boring, repetitive chunks of the genome, which correspond to those regions of solid color in a jigsaw puzzle), representing 198 megabytes of stuff that still has to be sequenced. In the euchromatin (the more interesting and complex stuff) there are more gaps, 308, but they are much smaller, so only 28 Mb of mystery remains. The total length of the genome is 3.08 Gb, with 2.88 Gb of it in the form of euchromatin.

The new, better defined sequence allows for a more accurate count of total gene number, and that number has dropped once again. We're down to 20-25,000 protein-coding genes. Some may think that knocks us off our pedestal a bit more, but that sounds like plenty to me.

One thing that leaps out at anyone reading the announcement is the importance of evolution in analyzing and understanding the genome. They used alignment with the chimpanzee draft sequence, for instance, to search for deletions. They are identifying recent duplications by their degree of divergence from neighboring genes, and have found 1,183 new genes that have arisen since the human and rodent lineages split. They're tracking the death of genes by identifying sequences with small numbers of disabling mutations (we seem to be losing olfactory genes at a rapid clip, relative to rodents).

The bottom line is that the HGP has provided us with a better tool for all kinds of research.

Nonetheless, the euchromatic human genome can now be regarded as effectively known. The accuracy and completeness of the current near-complete human genome sequence has important consequences for biomedical research. It allows systematic searches for the causes of disease—for example, to find all key heritable factors predisposing to diabetes or somatic mutations underlying breast cancer—with confidence that little can escape detection. It facilitates experimental tools to recognize cellular components—for example, detectors for mRNAs based on specific oligonucleotide probes or mass-spectrometric identification of proteins based on specific peptide sequences—with confidence that these features provide a unique signature. It allows sophisticated computational analyses—for example, to study genome structure and evolution—with confidence that subtle results will not be swamped or swayed by noisy data. At a practical level, it eliminates tedious confirmatory work by researchers, who can now rely on highly accurate information. At a conceptual level, the near-complete picture makes it reasonable for the first time to contemplate systems approaches to cellular circuitry, without fear that major components are missing.

International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931-945.

20 Comments

Jeff Fourmyle · 21 October 2004

Of course, the HGP is "done" only if the human population has no genetic variability. It's the variability that provides phenotypic variations for natural selection to operate upon.

Only when the diversity of the human genome is characterized will we understand who we really are. People whose lives depend on naive understanding or who profit from misunderstanding are justifiably terrified at the thought.

Great White Wonder · 21 October 2004

Only when the diversity of the human genome is characterized will we understand who we really are.

Not even then. "Understanding who we really are" is a meaningless phrase.

Mike Hopkins · 21 October 2004

Human genome: End of the beginning is online for free. It is the "News and Views" commentary on the research paper in the same issue.

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charlie wagner · 25 October 2004

Paul wrote:

One thing that leaps out at anyone reading the announcement is the importance of evolution in analyzing and understanding the genome. They used alignment with the chimpanzee draft sequence, for instance, to search for deletions. They are identifying recent duplications by their degree of divergence from neighboring genes, and have found 1,183 new genes that have arisen since the human and rodent lineages split. They're tracking the death of genes by identifying sequences with small numbers of disabling mutations (we seem to be losing olfactory genes at a rapid clip, relative to rodents).

I wouldn't be so quick to pass out the party hats and the noisemakers. While the HGP has made fabulous strides towards sequencing the human genome, they have only scratched the surface of it's complexity and organization. One thing that has become clear is that it is not the genes themselves that are most important. (You may recall me saying this some time back). Since the same genes turn up over and over again in a wide range of organisms, one is hard pressed to attribute differences between various diverse organisms to genes alone. The organization and interrelatedness between genomic components is far more complex that anyone ever expected and it will take decades to unravel it's secrets. The bottom line is that regulation and expression are far more important than the genes themselves, and research in this area is in its infancy. Perhaps it would go faster if people could break away from the darwinian paradigm of mutation and selection that has been an impediment to understanding for far too long. Nevertheless, when a gene activates, when it turns off, and under what circumstances these events occur will turn out to be far more important than the coding of proteins. All of the variation we see may well be the result of regulatory differences in similar genetic sequences. What we are slowly learning is that it is practically impossible to predict gene expression from sequences alone. http://www.sciencemag.org/cgi/content/full/306/5696/632

Creationist Timmy · 25 October 2004

Perhaps it would go faster if people could break away from the darwinian paradigm of mutation and selection that has been an impediment to understanding for far too long.

That's why I'm eagerly awaiting Pasquale's immanent mathematical disproof of evolution. Then we can ditch the worthless Darwinism crap. Since Darwinism was introduced, we've hardly made any progress in biology. It's holding us back. That's how you can tell we're using the wrong paradigm--we can't get anywhere with it. Biology has hardly advanced beyond where it was in 1860.

Great White Wonder · 25 October 2004

Charlie writes

All of the variation we see may well be the result of regulatory differences in similar genetic sequences.

Assuming that is true, then surely you agree that small changes in gene sequences which are regulatory in nature may affect the expression patterns of many different genes. Whether you agree or not, scientist have this was true for years.

Perhaps it would go faster if people could break away from the darwinian paradigm of mutation and selection that has been an impediment to understanding for far too long.

A complete non-sequitur Charlie. The only impediment to scientists understanding of the genome and the proteome is technology and the ability of the human brain to teach computers how to analyze the vast amounts of information that is currently being obtained about the expression patterns of particular cells at particular times (not to mention the correlation of those patterns with the concentrations in human sera and tissue of various chemicals, and the correlation of those patterns and concentrations with disease states of interest to physicians and their patients). I wonder what the contribution of ID apologists will be to all of these studies, Charlie. Actually I know what the contribution will be: ZILCHO. Do you disagree, Charlie? If so, please put your money where you mouth is. Gambling isn't sinful. Bill Bennett said so.

Bob Maurus · 25 October 2004

Charlie,

I too am fascinated with the potential role Hox genes might have played in evolutionary history. Great possibilities there.

charlie wagner · 26 October 2004

Great White Wonder wrote:

Do you disagree, Charlie?

I was born into rock and roll and I grew up with folk music. The thought of listening to hip-hop or rap music was abhorent.... until today. http://launch.yahoo.com (click on Eminem video "Mosh")

charlie wagner · 26 October 2004

GWW wrote:

surely you agree that small changes in gene sequences which are regulatory in nature may affect the expression patterns of many different genes.

That is true.

The only impediment to scientists understanding of the genome and the proteome is technology and the ability of the human brain to teach computers how to analyze the vast amounts of information that is currently being obtained about the expression patterns of particular cells at particular times.

The human brain is a far more advanced computer than any now in existence. It has the additional advantage (yes, advantage) of being an analog computer, rather than a digital computer. Human insight is the most important tool in deciphering the "other" code in the genome, the regulatory code that is far more complex and inscrutable. Having a dogmatic, preconceived notion of how things ought to be cannot help but slow the process.

charlie wagner · 26 October 2004

GWW wrote:

I wonder what the contribution of ID apologists will be to all of these studies, Charlie. Actually I know what the contribution will be: ZILCHO. Do you disagree, Charlie?

Of course I do. ID apologists (as you call them) have already made huge contributions to these studies. You just refuse to acknowledge them. As I explained on several other occassions, it is not the research or the data that is the problem, it's the interpretation of this data. At the present time, much of the interpretation has been slanted towards the darwinian "weltanschauung" or world view. While many ID theorists don't do any actual lab research (neither do theoetical physicists and cosmologists), their input is gradually changing the way we look at the data and have gone a long way towards eroding a 19th century paradigm that is obsolete and useless in the 21st century.

Pim van Meurs · 26 October 2004

Of course I do. ID apologists (as you call them) have already made huge contributions to these studies. You just refuse to acknowledge them. As I explained on several other occassions, it is not the research or the data that is the problem, it's the interpretation of this data. At the present time, much of the interpretation has been slanted towards the darwinian "weltanschauung" or world view. While many ID theorists don't do any actual lab research (neither do theoetical physicists and cosmologists), their input is gradually changing the way we look at the data and have gone a long way towards eroding a 19th century paradigm that is obsolete and useless in the 21st century.
— Charlie

What have these ID apologists contributed other than an appeal to ignorance. How do we look at data differently when all ID apologists do is doubt any regularity/chance pathway without proposing anything scientifically relevant. Of course much of the interpretation has been 'slanted' towards Darwinian worldview because the theory is so well founded in fact and observation. Until ID can propose its own hypotheses there is little to be taken seriously scientifically Charlie. Claiming that life looks designed is just begging the question.

Russell · 26 October 2004

Charlie Wagner: ID apologists ... have already made huge contributions to these studies.*

*[for antecedent of "these studies" see comment #9105].

Oh lord. Here we go again. Can you name one? (Note: the contribution has to, in some way, flow from or depend on the ID perspective.)

charlie wagner · 26 October 2004

Russell wrote:

Can you name one?

Of course. My own work has clearly demonstrated that intelligent input is necessary for the evolution of highly organized structures, processes and systems. http://www.charliewagner.com/casefor.htm http://enigma.charliewagner.com

Great White Wonder · 26 October 2004

Charlie

I was born into rock and roll and I grew up with folk music. The thought of listening to hip-hop or rap music was abhorent . . . .

Damn, Charlie. Where were you when Public Enemy was huge?

Russell · 26 October 2004

Charlie Wagner: My own work has clearly demonstrated that intelligent input is necessary for the evolution of highly organized structures, processes and systems.

We went down that road before and concluded that "Nelson's Law" shows that life had to be engineered by humans.

I'm not convinced that's a "huge contribution". What else do you have?

Russell · 26 October 2004

(A "huge contribution" should be at the very least a publication in a respected peer-reviewed journal.)

PZ Myers · 26 October 2004

And not some lame repetitive review article that says nothing new, but only distorts prior work, either. Primary research. Data. Evidence. Real science.

Charles Darwin launched his big theory on the world with 30 years of careful, obsessive research behind it. The Discovery Institute can't be bothered with science when trying to promote their view, and instead put their case in the hands of lawyers.

charlie wagner · 26 October 2004

Russell wrote:

(A "huge contribution" should be at the very least a publication in a respected peer-reviewed journal.)

A peer-reviewed journal is about the *last* place I would look for new ideas.

Russell · 26 October 2004

A peer-reviewed journal is about the *last* place I would look for new ideas.

The old "bait'n'switch" appears again! We were talking about "huge contributions" (the definition of which, it seems to me, involves at least someone who recognizes him/herself as the "recipient"). Now we're looking for "new ideas". (Or, as the case may be, old ideas pitched as new ones).

steve · 26 October 2004

Charlie Wagner said: A peer-reviewed journal is about the *last* place I would look for new ideas.

I think we all could have guessed that.