Adaptationist hypotheses are sexy, but don't forget the null hypothesis!

Just because a trait exists, or some process happens, and I can come up with an adaptationist just-so-story to explain its significance, doesn't necessarily mean that that trait or process actually has any functional, adaptive significance! That old lesson, hammered into behavioral ecologists like me by Gould and Lewontin's classic paper from 30 years ago, it seems, must be learned all over again by a new generation of genomic biologists! So argues Michael White in this must-read essay on the fascinating phenomenon of Genomic Junk and Transcriptional Noise:

With hot, new technologies, biologists are taking higher-resolution snapshots of what's going on inside the cell, but the results are stirring up controversy. One of the most interesting recent discoveries is that transcription is everywhere: DNA is transcribed into RNA all over the genome, even DNA that has long been thought to have a non-functional role. What is all of this transcription for? Does the 'dark matter' of the genome have some cryptic, undiscovered function?

Unfortunately, in all of the excitement over possible new functions, many biologists have forgotten how to frame a null hypothesis - the default scenario that you expect to see if there is no function to this transcribed DNA. As a result, the literature is teeming with wild, implausible speculation about how our excess DNA might be beneficial to us.

So here, let's step back and look at what we expect from DNA when it's playing absolutely no functional role; in other words, let's look at the null hypothesis of genomic junk and transcriptional noise. We can then take our null hypothesis and use it to look at a fascinating new study of how genomic parasites sculpt transcription in our cells.

There is no such thing as inert DNA

What bothers me most about the recent hullaballoo over pervasive transcription is the tacit assumption that non-functional DNA has to be inert. This is a terrible assumption from both a biochemical and an evolutionary viewpoint. We have every reason to expect non-functional DNA to be noisy.

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[via Genomic Junk and Transcriptional Noise]

Now, I don't know a whole lot about what goes on inside cells and the intricacies of DNA transcription - so it is still news to me that there is so much more transcription going on than is actually "needed", a whole lot of transcriptional noise from non-coding regions of our genomes! But, as White argues so well, just because this non-coding DNA is getting transcribed doesn't mean it is no longer "junk" - all this transcription may simply be a result of basic biochemistry. Throw together a whole bunch of DNA and RNA polymerases, within the confined quarters of, say, a typical mammalian cell, and some of this stuff is bound to happen. So my genome-studying friends - excited as you are about the huge volumes of data you are drowning in and all these new discoveries, pause a moment to reflect on what it all means, and stop seeing function everywhere. Remember the NULL hypothesis, which, in this case, predicts transcriptional noise to occur all the time.

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Just little bit of G, T, C, A ...

An ass-shaking jam, indeed, from Bio-Rad, courtesy of Dr. Isis the Scientist!

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Why are all earthly lifeforms lefties?

What, you think you are not left-handed? Just because you favor your right hand to write/eat/pitch that baseball, etc.? Actually, in case you didn't already know this: deep down, at the amino acid level, we are all lefties! Southpaws, each and every one of us! That's just another one of those wonderfully weird arbitrary fact about life on earth! Amino acids, the building blocks of proteins, are fundamental to the structure and function of life as we know it on our planet (which is pretty much how we know life at all, because we haven't found any other kind - yet!) - and the atoms making up each molecule can be put together in different ways to produce configurations which are mirror-images of each other (chirality, as the chemists call it); we know this because we can make amino acids in the lab. Yet, all life-forms we know of only contain one version of the amino acids - the left-handed one from the mirror-image pair! So this is another deep molecular homology involving amino acids (like the language of the genetic code we discuss in Evolution class), which unites all life-forms on this planet with a shared common ancestor. But there is no inherent reason why that ancestor had to be a southpaw in its use of amino acids. Was it just a random accident that that is how we turned out? A new study of the famous Murchison meteorite takes on the question...

Did lefty molecules seed life? (as reported in The Scientist today): "Amino acids come in left-handed and right-handed forms, which, like a pair of human hands, are mirror images that cannot be superimposed onto each other. Yet living organisms use only the left-handed version, which presents a conundrum: There's no biochemical reason why one mirror image should be better than the other, so scientists have long debated whether life's left-handed leaning arose because of random processes or whether rocks from outer space seeded a southpaw solar system."

...and suggests an explanation: that there was a left-bias in the amino acids that rained onto early earth from our solar system!

The current study argues for the latter possibility by showing that some extraterrestrial meteorites contain an abundance of left-handed molecules. "The implications are that all life in our solar system could be the same handedness as life on Earth," Jeffrey Bada, a geochemist at the Scripps Institution of Oceanography in La Jolla, Calif., who was not involved in the research, told The Scientist.

Daniel Glavin and Jason Dworkin, astrobiologists at NASA's Goddard Space Flight Center in Greenbelt, MD, compared the ratio of left- and right-handed 5-carbon amino acids found in six primitive, carbon-rich meteorites that have an elemental composition similar to that presumably found in the early solar system. Three of these rocks were heavily left-skewed, while the remaining three showed equal handedness, or chirality, the researchers found. Of the lefty rocks, the meteorite that fell on Murchison, Australia, in 1969 -- arguably the most widely studied carbonaceous meteorite in the world -- contained the largest imbalance ever observed: a 18.5% excess of the left-handed form of the amino acid isovaline.

Or, in their own words from the abstract of the PNAS paper:

The large asymmetry in isovaline and other α-dialkyl amino acids found in altered CI and CM meteorites suggests that amino acids delivered by asteroids, comets, and their fragments would have biased the Earth's prebiotic organic inventory with left-handed molecules before the origin of life.

Amino acids found in these and other meteorites landing on earth tend to exhibit a bias favoring left chirality, suggesting our entire solar system has the same left-bias, setting life as we know it on its lefty path. And Glavin & Dworkin think they know what favored left chirality in the meteorites:

The mechanism that Glavin and Dworkin propose to explain the observed left-handed excess is that polarized light -- which is twisted and can rotate molecules -- probably set the imbalance in motion. Then, once the balance was slightly askew, water within the meteorites further drove an enrichment of left-handed amino acids in the liquid phase and relegated right-handed molecules to the solid phase. "The whole amplification is due to this process of aqueous alteration," said Dworkin.

Not everyone is convinced, yet, but the search for answers to these puzzles about life's origin continues. (Or we could simply say goddidit, and stop asking any further questions, couldn't we? but where's the fun in that?)

Reference:

Glavin, D. P., & Dworkin, J. P. (2009). Enrichment of the amino acid l-isovaline by aqueous alteration on CI and CM meteorite parent bodies Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0811618106

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