Hey phenotypes – get with it!

With that headline I’m chiding myself – see Donna wrote today saying:

Wasn’t the Tues. Science Section in the Times amazing….the one about genes? Take that huge diagram of human chromosome 23, I believe it was, and its extraordinary minute levels of organization, and to think that this informational unit guides the formation of the phenotype*, or, of all of us folks emailing each other out here.

*phenotype - "the visible appearance or set of traits of an organism, resulting from the combined action of genotype and environment" (Yeah, I had to look it up so maybe some of you did as well. 😉

Whoops – missed that one – and what stories to miss. What the heck was I doing Tuesday, anyway? If you missed them as well, here’s a little of the flavor with some appropriate links.

I owe an apology to my genes. For years I offhandedly blamed them for certain personal defects conventionally associated with one’s hereditary starter pack — my Graves’ autoimmune disease, for example, or my hair, which looks like the fibers left behind on the rim of an aspirin bottle after the cotton ball has been removed, only wispier.
Now it turns out that genes, per se, are simply too feeble to accept responsibility for much of anything. By the traditional definition, genes are those lineups of DNA letters that serve as instructions for piecing together the body’s proteins, and, I’m sorry, but the closer we look, the less instructive they seem, less a “blueprint for life” than one of those disappointing two-page Basic Setup booklets that comes with your computer, tells you where to plug it in and then directs you to a Web site for more information.

Scientists have learned that the canonical “genes” account for an embarrassingly tiny part of the human genome: maybe 1 percent of the three billion paired subunits of DNA that are stuffed into nearly every cell of the body qualify as indisputable protein codes. Scientists are also learning that many of the gene-free regions of our DNA are far more loquacious than previously believed, far more willing to express themselves in ways that have nothing to do with protein manufacture.

and I love this. . . wonder if she’s thinking of Cheney or Biden . . .

In fact, I can’t even make the easy linguistic transition from blaming my genes to blaming my whole DNA, because it’s not just about DNA anymore. It’s also about DNA’s chemical cousin RNA, doing complicated things it wasn’t supposed to do. . . RNA is like the vice presidency: it’s executive, it’s legislative, it’s furtive.

OK – I’m in danger of quoting the whole article – but I’ve been having conversations about DNA with a very bright, very articulate biologist friend for years – been reading some basic books lately as well – yet this perspective is news to me:

Dr. Keller is a big fan of the double helix considered both in toto and in situ — in its native cellular setting. “DNA is an enormously powerful resource, the most brilliant invention in evolutionary history,” she said. “It is a far richer and more interesting molecule than we could have imagined when we first started studying it.”

Still, she said, “it doesn’t do anything by itself.” It is a profoundly relational molecule, she said, and it has meaning only in the context of the cell. To focus endlessly on genes, she said, keeps us stuck in a linear, unidirectional and two-dimensional view of life, in which instructions are read out and dutifully followed.

Here’s the full article.

Happy birthday, dear Gene, though we hardly know you!

WHile the first article whetted my appetite – the second one filled me up and then some. It covers similar ground, but with a little more history and a lot more detail.

It turns out, for example, that several different proteins may be produced from a single stretch of DNA. Most of the molecules produced from DNA may not even be proteins, but another chemical known as RNA. The familiar double helix of DNA no longer has a monopoly on heredity. Other molecules clinging to DNA can produce striking differences between two organisms with the same genes. And those molecules can be inherited along with DNA.

The gene, in other words, is in an identity crisis.

This crisis comes on the eve of the gene’s 100th birthday. The word was coined by the Danish geneticist Wilhelm Johanssen in 1909, to describe whatever it was that parents passed down to their offspring so that they developed the same traits. Johanssen, like other biologists of his generation, had no idea what that invisible factor was. But he thought it would be useful to have a way to describe it.

And does this strike you as ambitious?

Hundreds of scientists are carrying out a coordinated set of experiments to determine the function of every piece of DNA in the human genome. Last summer they published their results on 1 percent of the genome — some 30 million “letters” of DNA. The genetic code is written in letters, like the title of the movie “Gattaca,” with each letter standing for a molecule called a base: guanine (G), adenine (A), thymine (T), cytosine (C). The Encode team expects to have initial results on the other 99 percent by next year.

Let’s see – 1 percent equals 30 million, so that leaves only about 2,970 million to go – hmmmm, 40 hours a week, 52 weeks minus vacation, minus sick days, minus water cooler time – yeah, i think we can get it done in a year. Wow! Kurzweil would be proud of these folks!

Encode’s results reveal the genome to be full of genes that are deeply weird, at least by the traditional standard of what a gene is supposed to be. “These are not oddities — these are the rule,” said Thomas R. Gingeras of Cold Spring Harbor Laboratory and one of the leaders of Encode.

Got it – weird is the new normal, so normal must be weird. Sounds like my life. Can we get Sarah Palin in to explain this for me? or maybe Joe the Plumber?

No – I’m not really making light of this – that’s just a defense mechanism to protect me from an overload of awe. I’m used to exploring unimaginably large – and complex -things and occasionally I look into the unimaginably small (as in quantum theory) and complex – and here we have the unimaginably small and living and complex and . . . well, where we’re going today in so many ways with so many bright people all at once just is numbing . . . if nothing else it lends tremendous credence to Kurzweil’s theories about exponential growth.

And now zombie genes!

But the line between the useless baggage and the useful DNA is hard to draw. Mutations can make it impossible for a cell to make a protein from a gene. Scientists refer to such a disabled piece of DNA as a pseudogene. Dr. Gerstein and his colleagues estimate that there are 10,000 to 20,000 pseudogenes in the human genome. Most of them are effectively dead, but a few of them may still make RNA molecules that serve an important function. Dr. Gerstein nicknames these functioning pseudogenes “the undead.”

There are some great graphics with this second article – but I find myself staring at them the way I do at Hubble Space Telescope photo – amazed, but dazed.

For example – if you understand this, bless you. When I look at this graphic I just go “wow” – yep, it’s complicated. But I include it here for all you folks who are better informed than I am.

If this all leaves you feeling you need to go back to square one, you’ll find me there. I’m still wrestling with “The Cartoon Guide to Genetics” by Larry Gonick & Mark Wheelis. It was recommended by my biologist friend, so I have confidence in its accuracy. And most important, it starts and pretty much stays on a level I can understand. 😉