Friday, September 19, 2008

An Example of Faulty Logic from Cold Spring Harbor

 
A press release from Cold Spring Harbor Laboratory promotes the work of Michael Zhang and Adrian Krainer who work with splicing factors. In a typical attempt to hype the significance of the work, the press release claims that each human gene has many different variants produced by alternative splicing [CSHL team traces extensive networks regulating alternative RNA splicing].

That may or may not be correct—I happen to think it's mostly an artifact of EST cloning—but that's not the point I want to make here. The main point is the rationalization explained thus,
Biologists involved in the Human Genome Project were frankly astonished to discover that everything that makes us human is the product of a set of only 23,000 or so genes.1 That number in itself, though several times smaller than prior estimates, is not shocking; it is the relative size of other genomes that surprised scientists.

The common fruit fly that hovers over your ripening bananas, for instance, possesses some 14,000 genes. It's perfectly obvious that human beings are vastly more complex, biologically, than a fly. Molecular biologists have demonstrated in recent years that it is not the number of genes that is the key to complexity but rather the number and diversity of gene products that a given set of genes can instruct cells to manufacture.

Rather than a single gene ordering the production of a single kind of protein, as scientists used to assume, it turns out that individual genes can in some cases give rise to dozens or even thousands of different proteins, thanks to a phenomenon called alternative splicing.
This is one version of what I call The Deflated Ego Problem. The "problem" is that some people are really, really, upset about the fact that humans may only have a few thousand genes more than a fruit fly.

So they look for some way to reflate their egos and one of the most common arguments is the one shown above. (It's excuse #1 on the list.) It goes like this.... Humans are so much more complex that fruit flies even though they have only a few thousand more genes because each human gene does double, or triple duty. Each human gene makes several different proteins by alternative splicing of the primary RNA transcript.

Viola! Problem solved.

Except for one little nasty fact. Drosophila genes also show abundant levels of alternative splicing. In fact they produce just as many variants per gene as humans, if you believe the EST data (which I don't).

Oops. There goes that solution. Humans don't have that many more proteins than fruit flies after all.

This is such an obviously bogus argument that I'm surprised it still appears in the scientific literature. Doesn't anyone realize that in order for it to salvage deflated egos there has to be no—or much less— alternative splicing in fruit flies?


Some people were surprised and embarrassed by the "low" number of genes in the human genome but others were pretty happy that their estimates were close to the mark [Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome].

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