Rethinking junk DNA

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Teleological (July 16, 2009, 09:27:49 AM):
Transcriptomics: Rethinking junk DNA
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When the complete sequence of human chromosome 22 was first published in 1999 (ref. 4), John Rinn, an assistant professor at Beth Israel Deaconess Medical Center and an associate member of the Broad Institute in Cambridge, Massachusetts, got very excited. He was not interested in looking at the map of known protein-coding genes on the chromosome, but rather everything else. "We wanted to see if we could find biologically active molecules in the human genome that no one previously knew about," he says.

Armed with the sequence of an entire chromosome — and a year later the whole human genome — researchers and developers began to create genome-wide tiling microarrays. "By probing these tiling arrays we found out that there are tonnes of biologically active regions by proxy of RNA being made," says Rinn — results he and his colleagues reported in 2003 (ref. 5). Since then, Rinn has focused his efforts on understanding a collection of these RNAs known as large intervening non-coding RNAs (lincRNAs).

"Initially many people thought that this had to be an artefact of the technology: how could there be so many RNA molecules that we have never seen before?" says Rinn. Arguments against a true biological purpose for lincRNAs came largely from the lack of evolutionary conservation within their sequences — conservation implies function, whereas lack of conservation can often imply noise.

As so few functional lincRNAs had been described, Rinn and his colleagues set out to find more. In 2007 they reported the identification of a new 2.2-kilobase large non-coding RNA, which they called HOTAIR. It played a role in the guiding of chromatin complexes within the cell6. Although only a single new functional lincRNA — and still only one of four known to be functional at the time — the discovery gave Rinn an idea on how to enrich for functional lincRNAs from the genome.

[SIZE="2"]J. RINN

HOTAIR is one of an increasing number of functional non-coding RNAs identified from the human genome.[/SIZE]

"What we did next was to go after things that looked like HOTAIR," he explains. Instead of using an RNA-based approach, the group decided to look at chromatin structure. Histones have clear indications of where active genes start and stop. Using high-throughput chromatin immunoprecipitation (ChIP) sequencing on the Illumina Genome Analyzer to look for these marks, Rinn and his colleagues at the Broad Institute developed genome-wide chromatin state maps. Then, just as with his analysis of chromosome 22 almost ten years ago, Rinn says he threw out the known protein-coding genes and looked at what was left. He identified 1,600 other RNAs located by themselves in the middle of nowhere in the genome that look just like HOTAIR7.

To determine if some of their newly discovered RNAs were functional, the team took a 'guilt by association' approach, using microarrays to profile a number of the newly identified lincRNAs in 21 different tissue samples while at the same time profiling protein-coding genes in the same tissue samples.

Then they asked the question: which RNAs had similar profiles to protein-coding genes of known function? Their initial analysis was followed by further validation using independent systems. "This has turbo-charged the field, as not only can we identify these things now but we can get a good idea of what they might be doing to test functional relationships," says Rinn.

For Rinn and his colleagues it is now time to muster all the force they can to explore these RNAs. "We are going to throw the Broad kitchen sink at them," says Rinn, who is teaming up with a number of scientific platforms at the Broad Institute to look at the effects of knocking down each newly discovered lincRNA.

N.B.
Teleological (July 16, 2009, 09:29:14 AM):
Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution
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Summary

We show that the nuclear architecture of rod photoreceptor cells differs fundamentally in nocturnal and diurnal mammals. The rods of diurnal retinas possess the conventional architecture found in nearly all eukaryotic cells, with most heterochromatin situated at the nuclear periphery and euchromatin residing toward the nuclear interior. The rods of nocturnal retinas have a unique inverted pattern, where heterochromatin localizes in the nuclear center, whereas euchromatin, as well as nascent transcripts and splicing machinery, line the nuclear border. The inverted pattern forms by remodeling of the conventional one during terminal differentiation of rods. The inverted rod nuclei act as collecting lenses, and computer simulations indicate that columns of such nuclei channel light efficiently toward the light-sensing rod outer segments. Comparison of the two patterns suggests that the conventional architecture prevails in eukaryotic nuclei because it results in more flexible chromosome arrangements, facilitating positional regulation of nuclear functions


So, a few years ago, some were under the misguided notion that some streches of DNA are just letfover junk as a result of blind undirected processes. Perhaps because of a faulty worldview... No doubt there are still strecthes of DNA that we have no function for, but should one assume that it is junk?
More from the article:

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Mouse rod cells look strikingly unusual even after simple staining with DAPI. In all mouse cells, including other retinal cells, it brightly stains several (usually six to seven) chromocenters adjoining the nuclear periphery or the nucleolus (Figure 1B), and a rim of condensed chromatin along the nuclear border (arrows). In contrast, rods have a single very large central chromocenter and no staining at the nuclear border. To understand the spatial organization of these unusual nuclei, we studied the distribution of euchromatin and heterochromatin using fluorescence in situ hybridization (FISH) for marker repetitive sequences.

Chromatin of Mouse Rod Nuclei Is Arranged in a Concentric Fashion According to Gene Density

Centromeres and telomeres were detected by FISH with the minor satellite repeat probe and pantelomere probe, respectively. In rod nuclei, clusters of centromeres (three to five per nucleus) were found only on the surface of the chromocenters; each centromere cluster was associated with a cluster of telomeres (Figure 1D). Since all mouse chromosomes are acrocentric, these clusters were obviously formed by the proximal telomeres that are directly adjacent to the centromeres. Distal telomeres were predominantly distributed in the layer of peripheral chromatin (Figure 1D, arrows). Other retinal cells had more (6–18) clusters of centromeres, and their distal telomeres were usually located in the inner nuclear regions (Figure 1D).

Next, we determined the spatial distribution of the repetitive sequences characteristic of the C, G, and R bands of mouse chromosomes, which correspond to subcentromeric satellite DNA (constitutive heterochromatin, present on all mouse chromosomes and localized to the chromocenters), gene-poor mid-late replicating noncentromeric heterochromatin (L1-rich heterochromatin), and gene-dense early-replicating chromatin (euchromatin), respectively. To this end, we used probes for MSR (C bands), L1 (the major class of the long interspersed repetitive sequences; G bands) and B1 (the major class of the short interspersed repetitive sequences related to human Alu sequences; R bands) (c.f. Waterston et al., 2002). The chromosomal distribution of the used probes was confirmed by FISH on metaphase spreads (Figure S1 available online). In rod nuclei, FISH on cryosections revealed a single MSR-positive chromocenter surrounded by a thick shell of L1-rich chromatin and a thin outer shell of B1-rich euchromatin (Figures 1C1 and 1E1). By contrast, ganglion cells (Figure 1F1), bipolar cells, and cones (Figures S2A and S2B) showed the conventional nuclear architecture: B1-rich gene-dense chromatin was found toward the interior of the nucleus, whereas L1-rich gene-poor chromatin adjoined the nuclear border and surrounded the chromocenters. This pattern was also found in cultured mouse embryonic fibroblasts, with the exception that we did not observe L1-rich chromatin around the chromocenters (Figure 1G1). Quantitative evaluation of the radial distribution (Figures 1E2–1G2) confirmed the dramatic difference in the spatial distributions of marker DNA sequences between rods and cells with the conventional nuclear architecture.

See the "R bands", repetitive sequences related to human Alu sequences?
Consider the following article (also the source):
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As an example, in humans there is one particular family of junk DNA called Alu sequences that are repeated some million times or so, and this one family alone accounts for about 5% of our DNA. There are numerous other examples.


Now what are the alu-like sequences doing in the eyes of mice? Well, the nuclear architecture specifically aids nocturnal vision. From the article:

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Inversion of Rod Nuclear Architecture Alters Light Transmission through the ONL

The correlation between the inverted nuclear architecture and night vision suggested that the inverted pattern might have an optical ramification. Nocturnal mammals see at light intensities a million times lower than those available during the day, and their rod photoreceptors possess a light sensitivity down to the level of a few photons (Sterling, 2003). This high sensitivity rests primarily on the high density and small size of the outer segments (OS, Figure 1A) and therefore demands a large number of rod cells, which increases the thickness of the ONL ([Sterling, 2003] and Williams and Moody, 2003 R.W. Williams and S.A. Moody, Developmental and genetic control of cell number in the retina. In: L.M. Chalupa and J.S. Werner, Editors, The Visual Neurosciences, MIT Press, Cambridge, MA (2003), pp. 65–78.[Williams and Moody, 2003]). The optimization of light transmission through the ONL could therefore provide crucial advantages for nocturnal vision.


Would science proceed better if one were to assume function and design and then try and figure out what it is and how it works than to assume junk that accumulated for no reason?

The example of previously thought "junk DNA" does provide an intriging example of how the latter style of thinking seems to fail.
Mefiante (July 16, 2009, 19:56:48 PM):
So, a few years ago, some were under the misguided notion that some streches [sic] of DNA are just letfover [sic] junk as a result of blind undirected processes. Perhaps because of a faulty worldview...



Would science proceed better if one were to assume function and design and then try and figure out what it is and how it works than to assume junk that accumulated for no reason?

The example of previously thought "junk DNA" does provide an intriging [sic] example of how the latter style of thinking seems to fail.


(Emphases added.)
Paraphrased: “Because there are things we don’t know, our worldview seeeeeems faulty to me, so let’s improve it by assuming intent and directed purpose behind everything, including that stuff that we don’t yet know or are unaware of.”

That’s a remarkably ignorant load of tritely anti-scientific tosh.

The epistemological elephant-in-the-room is that science succeeds by learning from and correcting its missteps precisely because as a body (and unlike an interminable succession of fanciful approaches), it won’t be drawn into futile chasings down of dragon’s breath before the dragon has been sufficiently well tagged and caged.

'Luthon64
cyghost (July 16, 2009, 20:23:39 PM):
Further more assuming function and design would simply be bad science. Science works via observation, hypothesis, testing, refining and adapting and developing a theory.

(assuming (he he) the hypothesis holds up that is.

As we all know, including the OP, ID is *not* science and peddling it as such in a science subforum is just badong. I am surprised at the audacity really.
Teleological (July 17, 2009, 08:18:24 AM):
What both of you seem to fail to notice is that the latter style of thinking is not scientific in any way either. BTW, 'Luthon64, don't you have better things to do than to engage with someone who has monotonous repetition, tawdry irrelevancies and illusory tu quoque deflections?

It is good manners after all to accuse another of the above... even though it adds zero to a constructive and civil exchange of ideas ???.

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