Midden DNA

Some people don’t like the term “junk DNA”, because they assume all that extra DNA in the human genome must be doing something. Some of those people are tenured faculty, members of the ENCODE project, and have trouble penning reasonable definitions of biological function.

Other people have experimental data to show that random sequences of DNA can be biochemically active without physiological effect, understand that the genome’s complexity resists easy classification, and can, simultaneously, understand that these swathes of non-functional DNA are valuable because they contain the history of our evolution.

In that light, I am going to propose that we abandon the misleading phrase “junk DNA” and adopt a word from archaeology used to describe piles of informative waste: midden*.

A midden…is an old dump for domestic waste which may consist of animal bone, human excrement, botanical material, vermin, shells, sherds, lithics (especially debitage), and other artifacts and ecofacts associated with past human occupation. The word is of Scandinavian via Middle English derivation, but is used by archaeologists worldwide to describe any kind of feature containing waste products relating to day-to-day human life. – Wikipedia

Now, if you want to call it midden DNA or the DNA midden, that I am happy to leave up to personal taste and style.

*A potential confusion might arise when researchers sequence DNA from biological samples in an actual midden heap – a risk with which I am willing to live.

“What is your quest?”

That thing where you indavertantly facilitate a polite-ish discussion between Michael Eisen and Ewan Birney about ENCODE’s claims regarding “biochemical function” in the genome using modified Monty Python and the Holy Grail* quotes:

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With a “wafer thin” side of Open Access:

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You can check out the Storify of the #MontyPythonidae edition of #SCInema here.

*An apropos and overused scientific metaphor itself.

Science Caturday: One Code, Two Code…

Like a DNA nucleotide, this LOLcat is capable of playing multiple roles. It is good for creation vs. evolution, and so much more. Global warming vs. something else? You are covered. Homeopathy vs. physics? Done. Duons vs. the genetic code? In the bag.

Duons vs. the genetic code? What is a duon?

Good question. A duon is a DNA nucleotide that can do two roles. This perhaps makes it a rather lame nucleotide. DNA nucleotides have a lot of potential tasks they can do (eg, help encode an amino acid, be part of a protein binding site, indicate a splice site, etc) as part of their role storing information in our cells. The idea that a nucleotide might be subject to evolutionary pressure from several different tasks simultaneously is nothing new.

There is, as Emily Willingham points out at Forbes, no real “duon” controversy outside the minds of the folks that wrote the press release (and, perhaps, John Stamatoyannopoulos, if the press release quote is accurate, which I suspect it might be based on his advocacy for the ENCODE Consortium’s “junk DNA is functional” boondoggle). These researchers have provided some evidence to support the hypothesis that evolutionarily conserved codon bias (using one codon, of the several possible for an amino acid, in the genetic code more than expected by chance) is due to selection to maintain transcription factor binding sites.

This is not an unreasonable hypothesis, but it is hardly shocking, hardly requires a new term, and is hardly a controversy.

Having your cake and eating it: more arguments over human genome function

My fellow F&P publican Josh Witten has drawn my attention to a rebuttal (PDF) of Graur et al’s rebuttal of claims made by ENCODE.

The authors, John Mattick and Marcel Dinger of the University of New South Wales, advance various claims to dispute the idea that most of the genome is non-functional, but here I’ll just focus on one:

We also show that polyploidy accounts for the higher than expected genome sizes in some eukaryotes, compounded by variable levels of repetitive sequences of unknown significance.

Uh, yeah. That’s the resolution to the C-value paradox, and it’s one reason why people argue that repetitive sequences, i.e. transposable elements, are, contra claims about ENCODE data, largely non-functional – because their numbers vary greatly between species with a similar biology. As Doolittle writes:

A balance between organism-level selection on nuclear structure and cell size, cell division times and developmental rate, selfish genome-level selection favoring replicative expansion, and (as discussed below) supraorganismal (clade-level) selective processes—as well as drift— must all be taken into account.

Reading into the paper, how is it possible that the following claims by Mattick and Dinger don’t contradict each other? Continue reading “Having your cake and eating it: more arguments over human genome function”

Finding function in the genome part 2: All function is local (almost)

Yesterday I wrote about why negative controls are important in a genome-scale search for functional DNA. Today, I’ll discuss the main focus of our recent work: understanding what makes a piece of DNA functional.

The particular DNA I’m interested in is known by not very functional term ‘cis-regulatory’ DNA – a term that requires six syllables, an italicized Latin prefix, and a hyphen. This is DNA that is crucial in gene decisions: cis-regulatory DNA helps to control when, where, and how much genes are expressed. This happens because cis-regulatory DNA serves as a landing pad for ‘transcription factors’, proteins that land on cis-regulatory DNA and control the expression of nearby (or sometimes not so nearby) genes.

The question that haunts me is this: why don’t transcription factors get lost? My worry follows from these three observations: Continue reading “Finding function in the genome part 2: All function is local (almost)”

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