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, or my hair, which looks like the fibres left behind on the rim of an aspirin bottle after the cotton ball has been removed, only wispier.
The map just got lost
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 line-ups 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 come with your computer, tell you where to plug it in and then direct you to a website for more information.
Illustration by Jayachandran / Mint
Scientists have learnt that the canonical “genes” account for an embarrassingly tiny part of the human genome: Maybe 1% of the three billion paired sub-units 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.
Blueprint in ‘excess baggage’
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. Not long ago, RNA was seen as a bureaucrat, the middle molecule between a gene and a protein, as exemplified by the tidy aphorism “DNA makes RNA makes protein”. Now, we find cases of short clips of RNA acting like DNA, transmitting genetic secrets to the next generation directly, without bothering to ask permission. We find cases of RNA acting like a protein, catalysing chemical reactions, pushing other molecules around or tearing them down. RNA is like the US vice-presidency: it’s executive, it’s legislative, it’s furtive.
For many scientists, the increasingly baroque portrait of the genome that their latest research has revealed, along with the muddying of molecular categories, is to be expected. “It’s the normal process of doing science,” says Jonathan R. Beckwith of Harvard Medical School. “You start off simple and you develop complexity.”
Nor are researchers disturbed by any linguistic turbulence that may arise, any confusion over what they mean when they talk about genes.
“Geneticists happily abuse ‘gene’ to mean many things in many settings,” says Eric S. Lander of the Broad Institute, a collaboration of Massachusetts Institute of Technology (MIT) and Harvard University, based in Cambridge, Massachusetts. In Lander’s view, it’s an occupational hazard. “We’re trying to parse an incredibly complex system,” he says. “It’s like the US economy. What are your functional units? Employees and employers? Consumers and producers? What if you’re a freelancer with multiple employers? Where do farmers’ markets and eBay map on to your taxonomy?”
“You can never capture something like an economy, a genome or an ecosystem with one model or one taxonomy,” Lander adds. “It all depends on the questions you want to ask. You have to be able to say, this is Tuesday’s simplification; Wednesday’s may be different, because incredible progress has been made by those simplifications.”
The new genetic language
For other researchers, though, the parlance of molecular biology is desperately in need of an overhaul, starting with the gene. “The language is historical baggage,” says Evelyn Fox Keller, a science historian and professor emeritus at MIT. “It comes from the expectation that if we could find the fundamental units that make stuff happen, if we could find the atoms of biology, then we would understand the process.”
“But the notion of the gene as the atom of biology is very mistaken,” adds Keller, author of The Century of the Gene and other books. “DNA does not come equipped with genes. It comes with sequences that are acted on in certain ways by cells. Before you have cells, you don’t have genes. We have to get away from the underlying assumption of the particulate units of inheritance that we seem so attached to.”
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 says. “It is a far richer and more interesting molecule than we could have imagined when we first started studying it.” Still, she says, “It doesn’t do anything by itself.” It is a profoundly relational molecule that has meaning only in the context of the cell.
“What makes DNA a living molecule is the dynamics of it, and a dynamic vocabulary would be helpful,” Keller says. Writing last year in the journal PloS One, Keller and David Harel of the Weizmann Institute of Science, Rehovot, Israel, suggested as an alternative to “gene” the word “dene”, which they said could be used to connote any DNA sequence that plays a role in the cell. So far, Keller admits, it has yet to catch on.
Complex as our genome is, it obviously can be comprehended: Our cells do it every day. Then again, physician and essayist Lewis Thomas once noted, his liver was much smarter than he was, and he would rather be asked to pilot a 747 jet 40,000ft over Denver than assume control of his liver. “Nothing would save me or my liver, if I were in charge,” he wrote.
GENES: THE LANGUAGE THAT USED TO BE
CHROMOSOME: A package of DNA. The human genome—all the DNA in the nucleus of each cell—is contained in 23 pairs of chromosomes.
DNA: The double-stranded molecule that contains all genetic information in almost all organisms. Deoxyribonucleic acid.
EPIGENETIC: An epigenetic influence is something other than the structure of DNA that affects inherited traits.
EPIGENETIC MARKS: Molecules attached to DNA that can determine whether genes are active and used by the cell.
EXON: What might be considered the heart of the classic gene—a segment of a gene that is transcribed by RNA as a first step in making a protein.
GENE: Originally, a gene was a factor that was passed down from parents to offspring and determined hereditary traits. By the 1960s, the gene was conceived of as a segment of DNA that carried the instructions for making a protein molecule. Offspring developed particular traits because they inherited certain versions of genes.
GENOME: All the genetic material in an organism. In humans, the genome contains at least three billion “letters” of DNA. The letters GATC stand for the nucleotide bases guanine, adenine, thymine and cytosine, which are read by the cell when genes are active.
INTRON: A segment of a protein-coding gene that is edited out of an RNA transcript.
NON-CODING RNA: Molecules of RNA produced from DNA that are not used to produce proteins.
PROTEIN: A molecule (like collagen or haemoglobin) composed of amino acids. The instructions for building a protein are encoded in several exons. Proteins carry out many of the chemical reactions in the body, including switching genes on and off.
PSEUDOGENES: Genes that can no longer produce proteins after being disabled by mutations. Some pseudogenes can still produce non-coding RNA.
RNA: Ribonucleic acid. A single-stranded molecule transcribed from DNA. RNA can act as a template for building proteins, a sensor for detecting signals, or a switch for turning genes off or on.
TRANSCRIPT: An RNA molecule copied from a segment of DNA.
©2008/ The New York Times
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