BehindTheMedspeak: 'You're dumb as a plant'

A new report, published today in Nature magazine by the International Human Genome Sequencing Consortium, gives evidence for why that might be.

Turns out humans have about 25,000 genes, about the same number as small flowering plants or pufferfish.

This radical downsizing of the human genome - up to now it was thought we had around 30,000-40,000 genes - makes us more or less run-of-the-mill in terms of numbers.

As Francis Collins, director of the National Human Genome Research Institute at the National Institutes of Health said, "We humans don't look very impressive in the competition."

Just goes to show it's what you do with what you have that matters.

Here's Nicholas Wade's story about the new findings, from today's New York Times.
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Human Gene Total Falls Below 25,000

A new and perhaps final report from the international consortium of laboratories that decoded the human genome has revised the estimated number of human genes sharply downward.

About 20,000 human genes have been identified, and up to 5,000 more may await discovery, the group is reporting today in the journal Nature.

This tally is considerably less than the 30,000 or so predicted by the consortium and its commercial rival, Celera, when they first described their draft genome sequences in February 2001.

The 30,000 figure was itself a surprising downgrade from the 100,000 human genes commonly said to exist as recently as five years ago, before the exact sequence of DNA units in the genome was decoded.

Coincidentally, French researchers are reporting in the same issue of Nature that they have decoded the genome of a biologically important fish, the spotted green pufferfish.

They say it has 20,000 to 25,000 genes, the identical range now estimated for humans.

How can it be that humans, seen by some as the apotheosis of creation, have the same number of genes?

The question is the more pressing because genes are subject to a rigorous "use it or lose it" rule.

Those not vital to an organism are quickly rendered useless by mutations.

Also, the human brain seems particularly dependent on genetic complexity, because about half of all human genes are active in brain tissue.

From the fishes' point of view, the problem may seem rather less acute.

Their large number of genes "may relate to the fact that fish today are one of the most successful families of vertebrate on earth," Dr. Hugues Roest Crollius of the French team said.

Along with Dr. Jean Weissenbach and colleagues, Dr. Crollius is reporting that sometime after 450 million years ago, when the ancestors of people and pufferfish took separate evolutionary paths, the puffer and most other fish doubled up their genome in some freak cellular accident.

Though some duplicate genes were shed, many were put to alternative uses, giving fish a special evolutionary advantage.

Humans have enjoyed no such doubling in the last half billion years, Dr. Crollius said.

People presumably overcame the relative poverty of their genetic patrimony by other means.

"Clearly, the complexity of the nervous system must derive from some other feature than the gene count," said Dr. Francis S. Collins, director of the federal agency that supports genome decoding in the United States.

One such feature is alternative splicing, the mechanism through which a single gene can generate several kinds of protein by selecting different combinations of the same set of building blocks.

More alternative splicing occurs in human cells than in those of lower animals like flies and worms, Dr. Crollius said.

Another way in which humans may get more out of their genes is through more sophisticated control.

Cells have a small set of regulatory genes that control the activity of all the other genes.

Although the main human genes have recognizable counterparts in fish, the regulatory genes seem to be different, Dr. Collins said.

Presumably human regulatory genes are more sophisticated and can construct greatly more complex structures like the human brain.

The lower number of human genes "doesn't disturb me in a conceptual way at all," Dr. Richard Axel, a biologist at Columbia, said.

Through alternative splicing and regulatory control, a few thousand genes can make trillions of combinations of proteins.

So starting with 20,000 or 30,000 genes makes no great difference to the complexity of what the cell's machinery can generate, Dr. Axel said.

At the time of its first report, the consortium that decoded the human genome had failed to close 147,821 gaps in the DNA sequence of the 24 pairs of human chromosomes.

These gaps, stretches of DNA resistant to the usual sequencing methods, have now been reduced to just 341.

The total size of the human genome is 3.08 billion units of DNA, the consortium now estimates.

Besides the 341 gaps, a special structural DNA at the center and tips of each chromosome continues to defy current sequencing.

The international consortium, principally laboratories in Britain and the United States, with contributions from China, France, Germany and Japan, spent $300 million to prepare the draft sequence of the human genome.

Trying to fill the gaps and other finishing work has taken $320 million more, Dr. Collins said.

The article today is probably the final report on the genome as a whole, he said, although work continues on specific aspects.

Closing the remaining 341 gaps is a research project for the future.

Celera's version of the human genome was not taken beyond the draft stage, in part because the company had difficulty finding subscribers when the government, believing that access to the human genome should be free, was making the consortium's work available free.

Celera's novel sequencing, however, has now become standard in decoding other genomes.

"Celera proved that the whole genome shotgun technique is both technically feasible and provides a dramatic cost-saving over the clone-by-clone approach," the consortium's method, Dr. Lincoln Stein of the Cold Spring Harbor Laboratory in Laurel Hollow, N.Y., writes in Nature.