The amazing design of the genome

_{Denyse O'Leary

November 14, 2015

Design inference, Genomics, News}

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Discussed as a design but believed, by dogma, not to be a design.

Genomes are so regularly represented as strings of letters-As, Gs, Cs, and Ts-that it’s easy to forget that they aren’t just abstract collections of data. They exist in three dimensions. They are made of molecules. They are physical objects that take up space-a lot of space.

Consider that the human genome is longer than the average human. It consists of around two meters of DNA, which must somehow fit into cells, whose nuclei are about 200,000 times narrower.

So it folds. And it folds in such a way that any given stretch can be easily unfolded, so the genes within it can be read and used. Knots are verboten, and anyone who has ever shoved headphones into their pockets will know how hard it is to scrunch an extremely long thread into a ball without knotting anything.
More.

An interesting fact about dogma is, once culturally accepted, it becomes an automatic thought stopper. It looks like design, and there is no alternative possibility if the universe and Earth are of the finite ages generally given (plus or minus 4 B yrs and 13 B yrs respectively.

We are not allowed to think it is design because … well, that’s religion! Karl Giberson’s territory!

Then Darwin’s magic is invoked. Dawkins’s guiding words about Darwinism have shaped many a career:

“My argument will be that Darwinism is the only known theory that is in principle capable of explaining certain aspects of life. If I am right it means that, even if there were no actual evidence in favour of the Darwinian theory (there is, of course) we should still be justified in preferring it over all rival theories.” — p. 287, Blind Watchmaker” (1986)

However, we talked to the fossils, and they said no. But we were told to shut up. Not any more.

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Comments

gpuccio @3 Eccellente esplicazione mio caro Dottore! Esattamente QED! Mile grazie!Dionisio_{November 15, 2015
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Here is the link to the paper: "A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping" http://www.cell.com/abstract/S0092-8674(14)01497-4 This paper is really important. Hi-C technique is revealing amazing details about the 3d architecture of chromatin. Again, as already discussed on another thread, the strong connection between chromatin architecture, transcription, and DNA replication emerges:
Two of the five interaction patterns are correlated with loci in compartment A (Figure S4E). We label the loci exhibiting these patterns as belonging to subcompartments A1 and A2. Both A1 and A2 are gene dense, have highly expressed genes, harbor activating chromatin marks such as H3K36me3, H3K79me2, H3K27ac, and H3K4me1 and are depleted at the nuclear lamina and at nucleolus-associated domains (NADs) (Figures 2D, 2E, and S4I; Table S3). While both A1 and A2 exhibit early replication times, A1 finishes replicating at the beginning of S phase, whereas A2 continues replicating into the middle of S phase. A2 is more strongly associated with the presence of H3K9me3 than A1, has lower GC content, and contains longer genes (2.4-fold). The other three interaction patterns (labeled B1, B2, and B3) are correlated with loci in compartment B (Figure S4E) and show very different properties. Subcompartment B1 correlates positively with H3K27me3 and negatively with H3K36me3, suggestive of facultative heterochromatin (Figures 2D and 2E). Replication of this subcompartment peaks during the middle of S phase. Subcompartments B2 and B3 tend to lack all of the above-noted marks and do not replicate until the end of S phase (see Figure 2D). Subcompartment B2 includes 62% of pericentromeric heterochromatin (3.8-fold enrichment) and is enriched at the nuclear lamina (1.8-fold) and at NADs (4.6-fold). Subcompartment B3 is enriched at the nuclear lamina (1.6-fold), but strongly depleted at NADs (76-fold).
(emphasis mine) And this is specially interesting, to me:
The CTCF-Binding Exapted SINEB2 Repeat in Mouse Shows Preferential Orientation with Respect to Loops In mouse, we found that 7% of peak anchors lie within SINEB2 repeat elements containing a CTCF motif, which has been exapted to be functional. (The spread of CTCF binding via retrotransposition of this element, which contains a CTCF motif in its consensus sequence, has been documented in prior studies [Bourque et al., 2008; Schmidt et al., 2012].) The CTCF motifs at peak anchors in SINEB2 elements show the same strong bias toward convergent orientation seen throughout the genome (89% are oriented toward the opposing loop anchor versus 94% genome-wide). The orientation of these CTCF motifs is aligned with the orientation of the SINEB2 consensus sequence in 97% of cases. This suggests that exaptation of a CTCF in a SINEB2 element is more likely when the orientation of the inserted SINEB2 is compatible with local loop structure.
(emphasis mine) So, retrotransposon activity is apparently "exapted" to achieve function. IOWs, (in ID terms), retrotransposons are used to design the genome. QED.gpuccio_{November 15, 2015
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link is broken: corrected link
There’s a Mystery Machine That Sculpts the Human Genome -Oct 20, 2015 Excerpt: Consider that the human genome is longer than the average human. It consists of around two meters of DNA, which must somehow fit into cells, whose nuclei are about 200,000 times narrower. So it folds. And it folds in such a way that any given stretch can be easily unfolded, so the genes within it can be read and used. Knots are verboten,,, In the 1970s, biochemists showed that this feat of extreme origami begins when DNA is wrapped around proteins called histones, creating what looks like a string of beads. This reduces the packing problem, but doesn’t come close to solving it. The wrapped DNA must be folded and twisted in ever more complicated (and as yet unknown) ways. Eventually, it forms large loops. “That was a total bombshell,” says student Suhas Rao who worked on the project. He, like many others, had assumed that loops form when two stretches of free-floating DNA randomly find each other and are fastened by a pair of CTCF proteins. But that can’t be right. If it was, the CTCF landing sequences would align in all four possible orientations, rather than the very specific one that Rao saw in his data. The loops must be forming in a completely different way, one that’s deliberate and controlled. ,,, “This is an important milestone in understanding the three dimensional structure of chromosomes, but like most great papers, it raises more questions than it provides answers,” http://www.theatlantic.com/science/archive/2015/10/theres-a-mystery-machine-that-sculpts-the-human-genome/411199/
bornagain_{November 14, 2015
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My argument will be that Darwinism is the only known [mechanistic] theory that is in principle capable of explaining certain aspects of life. [For certain other aspects of life other, non-Darwinian, theories are needed.] If I am right it means that, even if there were no actual evidence in favour of the Darwinian theory (there is, of course) we should still be justified in preferring it over all rival theories [except when those other theories are to be preferred]. Fixed it for him. Or made a hash of it. Comments?Mung_{November 14, 2015
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