I Don't Have Time for This!

 

The banner headline on the front page of The Toronto Star says, "U of T cracks the code." You can read the newspaper article on their website: U of T team decodes secret messages of our genes. ("U of T" refers to the University of Toronto - our newspaper thinks we're the only "T" university in the entire world.)

The hyperbole is beyond disgusting.

The work comes from labs run by Brendan Frey and Ben Blencowe and it claims to have discovered the "splicing code" mediating alternative splicing (Barash et al., 2010). You'll have to read the paper yourself to see it the headlines are justified. It's clear that Nature thought it was important 'cause they hyped it on the front cover of this week's issue.

The frequency of alternative splicing is a genuine scientific controversy. We've known for 30 years that some genes are alternatively spliced to produce different protein products. The controversy is over what percentage of genes have genuine biologically relevant alternative splice variants and what percentage simply exhibit low levels of inappropriate splicing errors.

Personally, I think most of the predicted splice variants are impossible. The data must be detecting splicing errors [Two Examples of "Alternative Splicing"]. I'd be surprised if more than 5% of human genes are alternatively spliced in a biologically relevant manner.

Barash et al. (2010) disagree. They begin their paper with the common mantra of the true believers.

Transcripts from approximately 95% of multi-exon human genes are spliced in more than one way, and in most cases the resulting transcripts are variably expressed between different cell and tissue types. This process of alternative splicing shapes how genetic information controls numerous critical cellular processes, and it is estimated that 15% to 50% of human disease mutations affect splice site selection.

I don't object to scientists who hold points of view that are different than mine—even if they're wrong! What I object to is those scientists who promote their personal opinions in scientific papers without even acknowledging that there's a genuine scientific controversy. You have to look very carefully in this paper for any mention of the idea that a lot of alternative splicing could simply be due to mistakes in the splicing machinery. And if that's true, then the "splicing code" that they've "deciphered" is just a way of detecting when the machinery will make a mistake.

We've come to expect that science writers can be taken in by scientists who exaggerate the importance of their own work, so I'm not blaming the journalists at The Toronto Star and I'm not even blaming the person who wrote the University of Toronto press release [U of T researchers crack 'splicing code']. I'll even forgive the writers at Nature for failing to be skeptical [The code within the code] [Gene regulation: Breaking the second genetic code].

It's scientists who have to accept the blame for the way science is presented to the general public.

Frey compared his computer decoder to the German Enigma encryption device, which helped the Allies defeat the Nazis after it fell into their hands.

“Just like in the old cryptographic systems in World War II, you’d have the Enigma machine…which would take an instruction and encode it in a complicated set of symbols,” he said.

“Well, biology works the same way. It turns out to control genetic messaging it makes use of a complicated set of symbols that are hidden in DNA.”

Given the number of biological activities needed to grow and govern our bodies, scientists had believed humans must have 100,000 genes or more to direct those myriad functions.

But that genomic search of the 3 billion base pairs that make up the rungs of our twisting DNA ladders revealed a meagre 20,000 genes, about the same number as the lowly nematode worm boasts.

“The nematode has about 1,000 cells, and we have at least 1,000 different neuron (cells) in our brains alone,” said Benjamin Blencowe, a U of T biochemist and the study’s co-senior author.

To achieve this huge complexity, our genes must be monumental multi-taskers, with each one having the potential to do dozens or even hundreds of different things in different parts of the body.

And to be such adroit role switchers, each gene must have an immensely complex set of instructions – or a code – to tell them what to do in any of the different tissues they need to perform in.

I wish I had time to present a good review of the paper but I don't. Sorry.

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Barash, Y., Calarco, J.A., Gao, W., Qun Pan, Q., Wang, X., Shai, O., Benjamin J. Blencowe, and Frey, B.J. (2010) Deciphering the splicing code. Nature 465: 53–59. [doi:10.1038/nature09000] [Supplementary Information]