Tag Archives: Central Dogma of Molecular Biology

Maybe there really is junk DNA

Until about 20 years ago, molecular biology was incredibly protein-centric.  Consider the following terms — nonsense codon, noncoding DNA, junk DNA.  All are pejorative and arose from the view that all the genome does is code for protein.  Nonsense codon means one of the 3 termination codons, which tells the ribosome to stop making protein.  Noncoding DNA means not coding for protein (with the implication that DNA not coding for protein isn’t coding for anything).

The term Junk DNA goes back to the 60s, a time of tremendous hubris as the grand biochemical plan of life was being discovered. People were not embarrassed to use the term ‘central dogma’ which was DNA makes RNA makes protein. It therefore came as a shock once we had a better handle on the size of the genome to discover that less than 2% of it coded for protein. Since much of it was made of repetitive sequences it was called junk DNA.

I never bought it, thinking it very dangerous to dismiss as unimportant what you did not understand or could not measure. Probably this was influenced by my experience as an Air Force M.D. ’68 – ’70 during the Vietnam war.

But now comes a sure to be contentious but well reasoned paper arguing that junk DNA does exist, even though it is occasionally transcribed [ Cell vol. 183 pp. 1151 – 1161 ’20 ]. The paper discusses all RNAs in the cell not part of the ribosome, or small nucleolar RNAs (snoRNAs) or microRNAs.

They note that no enzyme is perfect acting on only the substrate we think evolution optimized it for — they call this promiscuous behavior. So a transcription factor which binds to a particular promoter sequence will also bind to near miss sequence. Moreover such near misses are constantly being generated in our genome by random mutation. This is why they think that the ENCODE (ENCyopedia Of Dna Elements) found that the entire genome is transcribed into RNA. The implication made by many is that this must be functional.

However many random pieces of DNA can activate transcription [ Genes Dev. vol. 30 pp. 1895 – 1907 ’16 ] producing what the authors call transcriptional noise.

There is evidence that the cell has evolved a way to stop some of this. U1 snRNP recognizes the 5′ splice site motif. It is present in nuclei at an order of magnitude higher than other spliceosomal subcomplexes, so it monitors for RNAs which have a 5′ splice site motif but which lack the 3′ splice site. These RNAs are subsequently destroyed, never making it out of the nucleus.

They think the primary function of lncRNA is chromatin remodeling affecting gene expression — this is certainly true of XIST which silences one of the two X chromosomes females carry.

There is a lot more very technical molecular biology and close reasoning in the paper, but this should be enough to whet your interest. It is well worth reading. Probably, like me, you’ll be mentally arguing with the authors as you read it, but that’s the sign of a good paper.

Now for a question which has always puzzled me. Consider the leprosy organism. It’s a mycobacterium (like the organism causing TB), but because it essentially is confined to man, and lives inside humans for most of its existence, it has jettisoned large parts of its genome, first by throwing about 1/3 of it out (the genome is 1/3 smaller than TB from which it is thought to have diverged 66 million years ago), and second by mutation of many of its genes so protein can no longer be made from them. Why throw out all that DNA? The short answer is that it is metabolically expensive to produce and maintain DNA that you’re not using

If you want a few numbers here they are:
Genome of M. TB 4,441,529 nucleotides
Genome of M. Leprae 3,268,203 nucleotides

Clearly microorganisms are under high selective pressure, and the paper says that humans are under almost none, but it seems to me that multicellular organisms would have found a way to get rid of DNA it doesn’t need.

It may well be that all this DNA and the RNA transcribed from it is evolutionary potting soil, waiting for some new environmental stress to put it to use.

The New York Times and NOAA flunk Chem 101

As soon as budding freshman chemists get into their first lab they are taught about significant figures. Thus 3/7 = .4 (not .428571 which is true numerically but not experimentally) Data should never be numerically reported with more significant figures than given by the actual measurement.

This brings us to yesterday’s front page story (with the map colored in red) “2014 Breaks Heat Record, Challenging Global Warming Skeptics“. Well it did if you believe that a .02 degree centigrade difference in global mean temperature is significant. The inconvenient fact that the change was this small was not mentioned until the 10th paragraph. It was also noted there that .02 C is within experimental error. Do you have a thermometer that measures temperatures that exactly? Most don’t, and I doubt that NOAA does either. Amusingly, the eastern USA was the one area which didn’t show the rise. Do you think that measurements here are less accurate than in Africa, South America Eurasia? Could it be the other way around?

It is far more correct to say that Global warming has essentially stopped for the past 14 years, as mean global temperature has been basically the same during that time. This is not to say that we aren’t in a warm spell. Global warming skeptics (myself included) are not saying that CO2 isn’t a greenhouse gas, and they are not denying that it has been warm. However, I am extremely skeptical of models predicting a steady rise in temperature that have failed to predict the current decade and a half stasis in global mean temperature. Why should such models be trusted to predict the future when they haven’t successfully predicted the present.

It reminds me of the central dogma of molecular biology years ago “DNA makes RNA makes Protein”, and the statements that man and chimpanzee would be regarded as the same species given the similarity of their proteins. We were far from knowing all the players in the cell and the organism back then, and we may be equally far from knowing all the climate players and how they interact now.