At The Scientist: “Junk RNA” is top science news in 2019

January 2, 2020January 2, 2020 NewsComments(48)

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A “completely unknown biology,” says a researcher. The paper on “glycoRNAs, or noncoding RNA strung with complex sugars called glycans” is still in preprint:

“There really is no framework in biology as we know it today that would explain how RNA and glycans could ever be in the same place at the same time, much less be connected to each other,” senior author Carolyn Bertozzi, a chemical biologist at Stanford University, told The Scientist in October.
Kerry Grens, “The Science News that Shaped 2019—“A completely unknown biology” ” at The Scientist

Remember when all that non-coding stuff was a vast library of junk that was evidence for Darwinian evolution?

48 Replies to “At The Scientist: “Junk RNA” is top science news in 2019”

1

Bob O'H says:

January 2, 2020 at 9:08 am

Junk RNA? The Scientist doesn’t mention junk in either the article linked to, or the original report.
2

PaV says:

January 2, 2020 at 12:21 pm

Bob O’H:

Here’s the start of the little blurb on this discovery:

Although still in preprint form, results published this fall introduced a new aspect to cell biology: glycoRNAs, or noncoding RNA strung with complex sugars called glycans.

Biologists are too embarassed to call “non-coding RNA” what once it was called, “Junk DNA.” But everyone around here remembers the argument. We remember the ENCODE project. We remember all the protestations. And we remember how wrong biologists were.
3

Bob O'H says:

January 2, 2020 at 1:08 pm

Biologists are too embarassed to call “non-coding RNA” what once it was called, “Junk DNA.”

Of course they would be. It would show they were utterly clueless about basic biochemistry.
4

martin_r says:

January 2, 2020 at 1:37 pm

this post mentioned so called ‘glycans’….
honestly, how many of you heard of glycans and the glycome ?

from NewScientist:

“Move over, DNA. Life’s other code is more subtle and far more powerful

“Our cells use a sugary language to identify and interact with each other.

“It turns out that every type of cell in our bodies has a unique sugar coating.

“And whenever anything interacts with a cell, it must recognise that sugar code and use the appropriate secret handshake.”

“use the appropriate secret handshake.” ????

“use the appropriate secret handshake.” ????

in other words, to use a PASSWORD …

i am only a stupid mechanical engineer, but are biologists – natural science graduates – really suggesting, that cells use PASSWORDS ??? first DNA code, now this ?
and all that happened by random unguided natural process ?

It seems that biologists really believe in miracles …

Someone should call the doctor…

Full article is here:
https://www.newscientist.com/article/mg24132230-300-move-over-dna-lifes-other-code-is-more-subtle-and-far-more-powerful/
5

Silver Asiatic says:

January 2, 2020 at 2:49 pm

Bob O’H

Of course they would be. It would show they were utterly clueless about basic biochemistry.

From a paper

Non-coding RNA: what is functional and what is junk?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306305/
Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.

Dr. Palazzo has received several awards and is an editorial board member of the journal PLoS One.

It’s good to know that he’s clueless about biochemistry. It must certainly be true of everyone else he is connected to.
We might be tempted to pay attention to something they said.
6

Bob O'H says:

January 2, 2020 at 4:01 pm

Silver Asiatic – read what PaV wrote carefully.
7

OLV says:

January 2, 2020 at 5:09 pm

Martin_r @4:

Excellent insightful commentary! Thanks!
8

OLV says:

January 2, 2020 at 5:10 pm

From this OP:

“A completely unknown biology” huh?
Glycans May Bind to RNA?

Although still in preprint form, results published this fall introduced a new aspect to cell biology: glycoRNAs, or noncoding RNA strung with complex sugars called glycans. Glycans are normally sequestered in the endoplasmic reticulum and Golgi bodies, away from RNA in the cytoplasm and nucleus.

“There really is no framework in biology as we know it today that would explain how RNA and glycans could ever be in the same place at the same time, much less be connected to each other,” senior author Carolyn Bertozzi, a chemical biologist at Stanford University, told The Scientist in October.

“Whatever it is, it’s a completely unknown biology.” Expect to see more insight into this mysterious new cellular entity—its function, its structure, and its prevalence.

Mammalian Y RNAs are modified at discrete guanosine residues with N-glycans

these findings suggest the existence of a ubiquitous interface of RNA biology and glycobiology suggesting an expanded role for glycosylation beyond canonical lipid and protein scaffolds.

The framework in which glycobiology is presently understood excludes RNA as a substrate for N-glycosylation.

Our discovery of glycoRNA suggest this is an incomplete view and points to a new axis of RNA glycobiology, including unprecedented enzymology, trafficking, and cell biology.

For the first time, scientists have found that complex sugars called glycans may bind to some RNA molecules,

The findings could substantially alter the current perception of RNA’s function.

“There really is no framework in biology as we know it today that would explain how RNA and glycans could ever be in the same place at the same time, much less be connected to each other,” senior author Carolyn Bertozzi, a chemical biologist at Stanford University, tells The Scientist.

a surprising finding that the researchers had never seen before.

“It was a really weird discovery. At first we were skeptical. . . We tried to shoot it down in every way that we could think of, and it just kept holding up,” says Bertozzi.

The researchers don’t yet know how the RNA and the sugars are bound

“Whatever it is, it’s a completely unknown biology,” says Bertozzi.

“This paper, if verified, would certainly open up an entirely new direction of research investigating gene expression, gene regulation, quality control of transcription, and RNA turnover,”

“I was surprised and excited to see it. It’s an unexpected and thought-provoking observation,” says Torsten Krude at the University of Cambridge

“If the results are consistent and verified by others, and if it holds the test of time and scrutiny, it would be an exciting new aspect to RNA biology.”
9

OLV says:

January 2, 2020 at 5:14 pm

Silver Asiatic,

Thanks for the link you posted @5:

Non-coding RNA: what is functional and what is junk? (2015)

It is clear that the human genome contains a large number of functional ncRNAs. Indeed it is likely that the list of biologically validated ncRNAs, as listed in the LncRNA Database (Quek et al., 2014), will continue to grow. As others have pointed out, even if 10% of current lncRNAs prove to be functional, this would represent a wealth of new biology. However, given our current understanding of biochemistry and evolution, it is likely that most of the RNAs generated from the low levels of pervasive transcription, and likely a substantial number of currently annotated “lncRNAs,” are non-functional.

An atlas of human long non-coding RNAs with accurate 5? ends (2017)

From this OP:

“Junk” DNA?
The Science News that Shaped 2019

With all the extensive investigations scientists have conducted of the human immune system over the past century, it is astonishing that there are still new cell types to be found.

scientists also reported that humans’ natural killer cells, thought to form the innate immune response, can also keep memories of past encounters with offending antigens, much like the adaptive immune response does.

The discovery challenges the basic dogma of how these cells function—another reminder there is still so much unknown even in our own blood.
10

Silver Asiatic says:

January 2, 2020 at 5:37 pm

I assumed that Bob O’H was trying to say something, but that was my mistake.
11

OLV says:

January 2, 2020 at 5:42 pm

An atlas of human long non-coding RNAs with accurate 5? ends (2017)

we identify 19,175 potentially functional lncRNAs in the human genome.

this study systematically elucidates the diversity of lncRNAs and summarizes the functional relevance of nearly 20,000 lncRNAs as an online resource, which can be further used in prioritizing lncRNA candidates for functional studies.

These observations support the notion that selectively more constrained lncRNAs are more likely to be functional, although it does not exclude the potential functionality of lncRNAs with weaker selective constraints.

Taken together, our analyses provide further evidence of the potential functionality of 69% of the FANTOM CAT lncRNAs (n = 19,175 of 27,919), advancing the current scientific debate on the functional relevance of pervasive transcription from mammalian genomes.

To what extent the remaining 31% represents spurious transcription initiation by RNA polymerase II is still an open question.

Although most of the lncRNAs detected here are likely to originate from genuine TSSs (Supplementary Note 6), additional studies are needed to completely understand their biogenesis and assess their functionality.

To this end, we have summarized their expression patterns, genomic features, conservation and intersection with genetic data into a comprehensive resource (http://fantom.gsc.riken.jp/cat/).

This encompasses a web application to retrieve gene-, trait- and cell-type-based information and ZENBU43 views for visualizing genomic data.

We anticipate wide applications of this resource in prioritizing lncRNA candidates for further elucidation of their functions, which is continuing in the sixth iteration of FANTOM (http://fantom.gsc.riken.jp/6/).
12

Silver Asiatic says:

January 2, 2020 at 5:46 pm

Thanks, OLV.

it is astonishing that there are still new cell types to be found.

It certainly must be astonishing for people who believe the lies they tell themselves.

The discovery challenges the basic dogma of how these cells function—another reminder there is still so much unknown even in our own blood.

Another reminder that the basic dogma is wrong and that the evolutionary high-priests should be held in contempt. It’s not only that so much is unknown, but that explanations on what is already observed are false and must be rejected.
13

OLV says:

January 2, 2020 at 5:47 pm

Silver Asiatic,

The information posted @9 & @11 is mostly a follow-up to what you posted @5.

Note the progression 2015-2017-2019.

Let’s see what we get in 2021.

🙂
14

Silver Asiatic says:

January 2, 2020 at 5:50 pm

Taken together, our analyses provide further evidence of the potential functionality of 69% of the FANTOM CAT lncRNAs (n = 19,175 of 27,919), advancing the current scientific debate on the functional relevance of pervasive transcription from mammalian genomes.

There’s a debate? Interesting.
This finding “advances the debate”.
I think that means, “one side keeps losing”.
15

OLV says:

January 2, 2020 at 5:50 pm

Silver Asiatic @12:

“It certainly must be astonishing for people who believe the lies they tell themselves”

Exactly! Good point. Thanks.
16

Silver Asiatic says:

January 2, 2020 at 5:51 pm

OLV

Let’s see what we get in 2021.

Thanks, yes. As above, the “debate”, keeps “advancing”.
I wonder when one side will eventually concede. Or will they hold out to the bitter end?
17

OLV says:

January 2, 2020 at 6:08 pm

Silver Asiatic and Martin_r:
Have you ever been in a long flight and have seen the stuffs attached to the back of the seat in front of you? One is used to place the food trays they serve for breakfast, lunch or dinner. Another -at the eyes level- is used to display information.
Now, let’s assume we don’t know what that stuff is for. We could get rid of all that stuff and test the plane to see if it flies. After confirming that the plane flies just fine without all that removed stuff, the airline starts to notice an increasing loss of passengers to other airlines that still have that “junk” attached to the back of the seats in long flights. That’s a surprisingly unexpected result, isn’t it? 🙂

Another way to look at this is by playing loud rock music to a crab dancing on a table. As we remove the crab legs one at a time we notice that the crab starts missing the rhythm and slows down considerably. After removing the last leg the crab stops dancing completely. Conclusion: the crab got completely deaf, hence its legs are associated with the hearing system. 🙂

Testing functionality is not a joke. It’s a serious task that must be done carefully and with open mind.
18

OLV says:

January 2, 2020 at 6:11 pm

Silver Asiatic @16:

“I wonder when one side will eventually concede. Or will they hold out to the bitter end?”

No, they won’t concede. They will hold out to the bitter end. It’s the nature of the human nature.

We must humbly admit that we can’t change it. C’est la vie, mon ami! 🙂
19

OLV says:

January 2, 2020 at 7:03 pm

Multimodal Long Noncoding RNA Interaction Networks: Control Panels for Cell Fate Specification (2019)

Lineage specification in early development is the basis for the exquisitely precise body plan of multicellular organisms. It is therefore critical to understand cell fate decisions in early development. Moreover, for regenerative medicine, the accurate specification of cell types to replace damaged/diseased tissue is strongly dependent on identifying determinants of cell identity.

Long noncoding RNAs (lncRNAs) have been shown to regulate cellular plasticity, including pluripotency establishment and maintenance, differentiation and development, yet broad phenotypic analysis and the mechanistic basis of their function remains lacking.

As components of molecular condensates, lncRNAs interact with almost all classes of cellular biomolecules, including proteins, DNA, mRNAs, and microRNAs.

With functions ranging from controlling alternative splicing of mRNAs, to providing scaffolding upon which chromatin modifiers are assembled, it is clear that at least a subset of lncRNAs are far from the transcriptional noise they were once deemed.

This review highlights the diversity of lncRNA interactions in the context of cell fate specification, and provides examples of each type of interaction in relevant developmental contexts. Also highlighted are experimental and computational approaches to study lncRNAs.
20

OLV says:

January 2, 2020 at 7:11 pm

Interactions between short and long noncoding RNAs

It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi?interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation.

As miRNAs and related small RNAs are already known to act in virtually every biological process in mammalian cells, and the spread of lncRNA influence is also increasing, it is likely that we will also see a dramatic increase in the known interactions between members of these two RNA classes. As lncRNAs are in general very similar in their structure and modifications to mRNAs, the modes and outcomes of their interactions with small RNAs also resemble those already seen with mRNAs, and indeed, none of the examples presented here, be it TDMD or cleavage by piRNAs appear to be unique to lncRNAs. As mentioned above, lncRNAs and mRNAs differ in their average abundance, stability, and localization, and these properties may affect the prevalence of their interactions with small RNAs, but it is important to keep in mind that there are thousands of lncRNAs that closely resemble mRNAs in each of those properties. Thus, the small?long RNA network, that is just now beginning to be uncovered, is expected to remain a vibrant and fertile ground for future discoveries, and potentially even therapeutic interventions in a wide array of contexts.
21

OLV says:

January 2, 2020 at 7:37 pm

Here’s a clear example of the shamefully negative consequences of the dogmatic reductionist approach to research influenced by the close-mindedness associated with some Darwinian ideas.

Interplay Between ncRNAs and Cellular Communication: A Proposal for Understanding Cell-Specific Signaling Pathways

Intercellular communication is essential for the development of specialized cells, tissues, and organs and is critical in a variety of diseases including cancer. Current knowledge states that different cell types communicate by ligand–receptor interactions: hormones, growth factors, and cytokines are released into the extracellular space and act on receptors, which are often expressed in a cell-type-specific manner. Non-coding RNAs (ncRNAs) are emerging as newly identified communicating factors in both physiological and pathological states. This class of RNA encompasses microRNAs (miRNAs, well-studied post-transcriptional regulators of gene expression), long non-coding RNAs (lncRNAs) and other ncRNAs. lncRNAs are diverse in length, sequence, and structure (linear or circular), and their functions are described as transcriptional regulation, induction of epigenetic changes and even direct regulation of protein activity. They have also been reported to act as miRNA sponges, interacting with miRNA and modulating its availability to endogenous mRNA targets. Importantly, lncRNAs may have a cell-type-specific expression pattern. In this paper, we propose that lncRNA–miRNA interactions, analogous to receptor–ligand interactions, are responsible for cell-type-specific outcomes. Specific binding of miRNAs to lncRNAs may drive cell-type-specific signaling cascades and modulate biochemical feedback loops that ultimately determine cell identity and response to stress factors.

Cancer is a complex disease and a major cause of death worldwide. Development of neoplastic disease is a multistep process involving the accumulation of numerous molecular changes. These changes impact cellular function within the tumor and its microenvironment, ultimately resulting in the hallmarks of cancer

To date, most researchers have aimed to define the molecular mechanisms of tumorigenesis and cancer progression based on the classical gene expression theory – transcription of coding genes followed by protein synthesis.

However, studies have mainly been based on around 20,000 protein-coding genes, corresponding to approximately 2% of the whole transcribed genome (Bertone et al., 2004; Carninci et al., 2005); the other transcripts include a large variety of non-coding RNAs (ncRNAs). Continuous generation of RNA sequencing (RNAseq) data shows that ncRNAs are strongly deregulated in pathological processes – particularly in multifactorial diseases like cancer (Cipolla et al., 2018). Hence, current limitations to deciphering the molecular mechanisms of cancer might be due to the fact that the putative implications of a large part of the genome remain undefined.

While ncRNA genes were for years considered as an irrelevant part the genome there is growing evidence that mammalian cells produce them in their thousands

in the absence of experimental verification of their function, most (>95%) of these transcripts are still considered transcriptional noise

the variety in their mode of action, ranging from protein activity regulation to epigenetic control and regulation of other ncRNAs, implies that we are just beginning to understand their importance for a multitude of biochemical and cellular functions.

It is therefore conceivable that elucidating the function of lncRNAs in normal cells and their deregulation in cancer cells will be one of the next milestones toward a more detailed understanding of the molecular mechanisms of cancer.

In summary, current limitations in our understanding on the molecular mechanisms of cancer might be due to the fact that, until now, only 2% of the genome has been taken into account. Therefore, future studies should aim at expanding our current view of cancer by including the role of ncRNAs in the interpretation of cancer as a multifactorial disease.
22

jawa says:

January 2, 2020 at 7:56 pm

Why don’t we see more ID objectors in this discussion?

Are they afraid of serious scientific discussions?

We know that a few distinguished biology or biochemistry professors* have commented here in this website before, but have left after running out of valid anti-ID arguments. ????

(*) professors LM (UofT) & AH (UofK) for example
23

Bob O'H says:

January 3, 2020 at 4:53 am

Jawa – I think most of us decide it’s not worth it. It’s been repeated many times that we know what a lot of “junk DNA” is, so we know it’s not functional for the organism (a lot of it is selfish transposable elements). We know a lot of it gets transcribed, but still isn’t functional for the organism. Finding another function for some non-coding DNA isn’t really a big deal evolutionarily: we already know a some of it has function.

This message never seems to get across, though. People around here seem to get triggered by “junk DNA” (as well as another phrase I used above: if you can’t guess what it is, just wait).
24

ET says:

January 3, 2020 at 9:24 am

Bob- your position cannot account for DNA based organisms. You have to be given them to start. And even then you don’t have a mechanism capable of producing eukaryotes given starting populations of prokaryotes. All you and yours have are arguments from extreme ignorance.

Good luck with that.
25

Silver Asiatic says:

January 3, 2020 at 11:37 am

Bob O’H

Finding another function for some non-coding DNA isn’t really a big deal evolutionarily: we already know a some of it has function.

I’m sure you recall when evolutionists (with the same kind of confidence you are showing here) stated that Junk DNA had no function. They used this as evidence for evolution. Later, the same evolutionists were “surprised” to find some function. They claimed it was less than 1% of ncDNA. Then later, they were less surprised when that percentage increased.
So, to say now “it’s no big deal” to find function makes sense, yes.
But what we’ve seen is a breakdown in credibility among those who made bold claims and were proven wrong. It seems that today’s bold claims will suffer the same consequences.
If I was a researcher, trying to convince the public and “get the message across”, I’d be a lot more apologetic about recent falsifications of my own claims.
My first response wouldn’t be “it’s no big deal”. I think that would just undercut credibility more and indicate that the researcher is arrogant and can’t admit his own ignorance and blind-spots.
26

Bob O'H says:

January 3, 2020 at 11:57 am

Silver Asiatic –

I’m sure you recall when evolutionists (with the same kind of confidence you are showing here) stated that Junk DNA had no function.

No, I don’t, even in the late 80s, when I started a Genetics degree and we didn’t know what junk DNA was.
27

Silver Asiatic says:

January 3, 2020 at 2:40 pm

Bob O’H

No, I don’t, even in the late 80s, when I started a Genetics degree and we didn’t know what junk DNA was.

My point is that you still don’t know what it is.
As for the 1980s, and claims prior to that …

A geneticist, Susumu Ohno, was the first to coin the term “junk” DNA in 1972. He used the term to refer to pseudogenes (commonly thought of as defunct relatives of known genes that do not code for proteins), but with time its meaning broadened to include all non-coding DNA (DNA that does not contain genes and does not produce proteins).1 Ohno stated, “The earth is strewn with fossil remains of extinct species; is it a wonder that our genome too is filled with the remains of extinct genes?” Due to his evolutionary presupposition, he assumed that non-coding DNA was merely a “genetic fossil” that may have been useful somewhere in our evolutionary past but had been discarded as we evolved into more complex, higher organisms. Since this “junk” DNA was no longer needed, it would not be under selective pressure, and mutations could accumulate without any harm to the organism.

Ohno believed that non-coding base sequences had no function. Thus the term “Junk”.

[he] tried to (mistakenly) construct a scientific argument that the human genome can not sustain more than a very limited number of “genes” and argued for “the importance of doing nothing” for the rest.

Ohno’s views
28

Bob O'H says:

January 3, 2020 at 4:12 pm

Silver Asiatic –

My point is that you still don’t know what it is.

Well, perhaps you should have written that, rather than “I’m sure you recall when evolutionists (with the same kind of confidence you are showing here) stated that Junk DNA had no function.” It’s difficult to respond to what you were trying to say when you actually say something different.

As for Ohno, you seem to be confusing one person’s opinions from the early 70s with what was known in the late 80s. Quite a lot happened between those two times.
29

Silver Asiatic says:

January 3, 2020 at 5:59 pm

Bob O’H

Well, perhaps you should have written that, rather than “I’m sure you recall when evolutionists (with the same kind of confidence you are showing here) stated that Junk DNA had no function.” It’s difficult to respond to what you were trying to say when you actually say something different.

Ok, I’m sorry I made that more difficult. Ohno – an evolutionist. Stated Junk DNA had no function. I think that’s an illustration of what I said. Evolutionists claimed that Junk DNA had no function, but in fact, they really didn’t know.

As for Ohno, you seem to be confusing one person’s opinions from the early 70s with what was known in the late 80s. Quite a lot happened between those two times.

In the 70s, Ohno claimed he knew what Junk DNA was, but he was wrong even though the name he gave it and his understanding of it was retained for a long while. Yes, as you said, in the late 80s, you didn’t know what Junk DNA was. Now you still don’t know. But you assured us that whatever we discover about it in the future will not be a “big deal”.
Given the points above, I can’t put a lot of trust in what you said.
30

OLV says:

January 3, 2020 at 7:53 pm

how did this appear on the scene?

Molecular choreography of pre-mRNA splicing by the spliceosome

The spliceosome executes eukaryotic precursor messenger RNA (pre-mRNA) splicing to remove noncoding introns through two sequential transesterification reactions, branching and exon ligation. The fidelity of this process is based on the recognition of the conserved sequences in the intron and dynamic compositional and structural rearrangement of this multi-megadalton machinery. Since atomic visualization of the splicing active site in an endogenous Schizosaccharomyces pombe spliceosome in 2015, high-resolution cryoelectron microscopy (cryo-EM) structures of other spliceosome intermediates began to uncover the molecular mechanism. Recent advances in the structural biology of the spliceosome make it clearer the mechanisms of its assembly, activation, disassembly and exon ligation. Together, these discrete structural images give rise to a molecular choreography of the spliceosome.

Since visualization of the first atomic structure of an intact spliceosome in 2015, all eight major functional states of the fully assembled spliceosome from S. cerevisiae and all but one such states from human have been structurally characterized (Table 1). The atomic structures of the pre-B, B, Bact, B*, C*, P, and ILS from S. cerevisiae recapitulate the process of spliceosome assembly, activation, catalysis, and disassembly. This information, together with structures of other spliceosomal complexes, give rise to a molecular choreography of pre-mRNA splicing by the spliceosome. Although many details remain to be elucidated through additional biochemical and biophysical studies, what we have already seen represents a remarkable achievement by cryo-EM in a fundamental area of biological research.
31

OLV says:

January 4, 2020 at 4:08 am

ID on steroids? 🙂

Sonic hedgehog in vertebrate neural tube development (2018)

The formation and wiring of the vertebrate nervous system involves the spatially and temporally ordered production of diverse neuronal and glial subtypes that are molecularly and functionally distinct. The chick embryo has been the experimental model of choice for many of the studies that have led to our current understanding of this process, and has presaged and informed a wide range of complementary genetic studies, in particular in the mouse. The versatility and tractability of chick embryos means that it remains an important model system for many investigators in the field. Here we will focus on the role of Sonic hedgehog (Shh) signaling in coordinating the diversification, patterning, growth and differentiation of the vertebrate nervous system. We highlight how studies in chick led to the identification of the role Shh plays in the developing neural tube and how subsequent work, including studies in the chick and the mouse revealed details of the cell intrinsic programs controlling cell fate determination. We compare these mechanisms at different rostral-caudal positions along the neuraxis and discuss the particular experimental attributes of the chick that facilitated this work.

The secretion, spread and reception of Shh within the neural tube depends on a large set of dedicated proteins, many of which are highly conserved

The route by which Shh protein is dispersed through the posterior neuroepithelium remains unclear.

microtubule based transport traffics Shh from the notochord across cells in the midline of the forming neural tube (the prospective floor plate), possibly in vesicles, to their apical surface, where it is released

it is clear that several extracellular and transmembrane proteins influence the spread of Shh protein through the neuroepithelium.

Collectively, the studies of the last two decades have revealed the multiple roles that Shh plays in the development of the vertebrate nervous system. Reciprocally, the analysis of neural tube development has provided multiple insights into Shh signaling. The chick embryo has featured prominently in many of these studies and through this work we have gained new mechanistic insights into how a single signal can perform several functions and produce an ordered pattern of diverse cell types in a complex tissue. Not only have these insights deepened our understanding of fundamental developmental processes but they have also been a major influence in the establishment of methods for the directed differentiation of specific neuronal subtypes from embryonic stem cells in vitro (Wichterle et al., 2002); Cundiff and Anderson, 2011; Liu and Zhang, 2010). Moreover the transplantation of stem cell-derived neurons back into chick has resulted in successful engraftment (Wichterle et al., 2002), raising the hope that this could provide an eventual route to cell based therapies for some neurodegenerative diseases.

Despite the progress, much remains to be discovered about Shh signaling and neural tube development. Approaches that provide live, high-resolution measurements of the activity of key components of the pathway are necessary to decipher the signaling mechanism and provide insight into the dynamics of signal transmission through the pathway. Similarly, understanding how Shh signaling regulates differential gene expression to control cell fate decisions will benefit from the increased precision and resolution that new technologies are beginning to offer. It seems likely that the chick will continue to play a leading role in these approaches.
32

OLV says:

January 4, 2020 at 4:36 am

More ID

Development of the basal hypothalamus through anisotropic growth

The adult hypothalamus is subdivided into distinct domains: pre?optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views…

Taken together, these studies suggest a new model for hypothalamic development that we term the “anisotropic growth model”. We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.

In summary, the final position of hypothalamic neurones does not necessarily reflect the position of their progenitors, which can migrate extensively. This highlights the importance of future lineage?tracing studies in determining the origin of individual hypothalamic neuronal classes in discrete nuclei.
33

Bob O'H says:

January 4, 2020 at 10:42 am

SA – I guess you’ve conceded that I can’t “recall when evolutionists (with the same kind of confidence you are showing here) stated that Junk DNA had no function.” And when did Ohno, even, state this? Certainly not in his So Much ‘Junk DNA’ in our Genome paper, where he suggests possible functions (an points to centromric sequences as non-coding but having a function).

And where did Ohno claim he knew what junk DNA was? He made some suggestions, but what he wrote was clearly speculative – he didn’t present a lot of empirical evidence (certainly not or what we now know as pseudo-genes). Of course, we now know that he was largely wrong – although there are pseudo-genes, we actually know that a lot of junk DNA is ERVs and the like – selfish DNA.
34

OLV says:

January 4, 2020 at 11:24 am

another evident ID showoff? 🙂

Multiplexing Genetic and Nucleosome Positioning Codes: A Computational Approach

Eukaryotic DNA is strongly bent inside fundamental packaging units: the nucleosomes. It is known that their positions are strongly influenced by the mechanical properties of the underlying DNA sequence.

the exact positions of nucleosomes play crucial roles in chromatin function.

DNA molecules are much longer than the cells that contain them. This requires their compaction, which introduces also an opportunity: the regulation of transcription through a differentiated fashion of DNA packaging. In eukaryotes DNA molecules can guide their own packaging into nucleosomes by having the desired mechanical properties (stiffnesses and intrinsic curvature) written into their base-pair (bp) sequence. This has been referred to as the “nucleosome positioning code”

As the DNA is strongly deformed when wrapped around the histones, sequence-dependent geometrical and mechanical properties could—at least locally—overrule other effects that also influence nucleosome positioning like the presence of proteins that compete for the same DNA stretch or the action of chromatin remodellers

Nucleosomes can thus be considered as a highly diverse class of DNA-protein complexes with a near continuous range of physical properties.
35

PaV says:

January 4, 2020 at 2:28 pm

Bob O’H:

There are now articles saying that transposable elements–what you seem to now consider as ‘junk,’ is the real driver of evolution.
36

Bob O'H says:

January 4, 2020 at 3:36 pm

Pav – Can you point to these articles? I’ll predict that that’s not what they say.
37

pw says:

January 5, 2020 at 12:43 am

DNA Transposons and the Evolution of Eukaryotic Genomes
https://www.annualreviews.org/doi/10.1146/annurev.genet.40.110405.090448
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pw says:

January 5, 2020 at 12:46 am

Diversification of the Caenorhabditis heat shock response by Helitron transposable elements
https://elifesciences.org/articles/51139
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pw says:

January 5, 2020 at 12:50 am

Helitrons on a roll: eukaryotic rolling-circle transposons
Helitrons seem to have a major role in the evolution of host genomes.
https://www.cell.com/trends/genetics/fulltext/S0168-9525(07)00270-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168952507002703%3Fshowall%3Dtrue
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Bob O'H says:

January 5, 2020 at 4:51 am

Thank you Pw, but I’m not sure those are the papers PaV was thinking of.

PaV claimed “There are now articles saying that transposable elements … is [sic] the real driver of evolution.”
What does “DNA Transposons and the Evolution of Eukaryotic Genomes” say?

Transposable elements occupy a large fraction of many eukaryotic genomes and their movement and accumulation represent a major force shaping the genes and genomes of almost all organisms.

So, a major source not “the real driver”. i.e. there are other sources, indeed other major sources.

Next, “Diversification of the Caenorhabditis heat shock response by Helitron transposable elements”. This doesn’t say anything about whether TES are a major force, or the major driver, of evolution. It does give one example where a transposon seems to play a large role in the evolution of stress responses.

So how about “Helitrons on a roll: eukaryotic rolling-circle transposons”? Does this show that TEs are “the real driver of evolution”? Alas not: what they do say is “Helitrons seem to have a major role in the evolution of host genomes.”.

So these don’t support PaV’s claim. Perhaps PaV himself has some references to back him up.
41

Silver Asiatic says:

January 5, 2020 at 12:08 pm

Bob O’H

Ohno created the term Junk DNA because he claimed that non-coding DNA had virtually no function.
He was proven wrong.
I’ve been responding to your statement:

Finding another function for some non-coding DNA isn’t really a big deal evolutionarily: we already know a some of it has function.

The falsification of Ohno’s claim was a big deal. His prediction based on evolutionary theory proved false.
Now you make a prediction stating that finding more functions for non-coding DNA is not a big deal.
At the same time, you don’t know what Junk DNA is.
So, your prediction has no substance and deserves no credibility.
You’re trying to make a prediction about an entity that you haven’t even understood fully yet.
From there, you use sophistry and hair-splitting to try to score a point.
That’s defensive and shows a lack of integrity in your theory itself. This is your life’s work – you shouldn’t need to nit-pick. But the failure of claims about non-coding DNA being Junk is now upheld as a failure for evolutionary theory so I understand your defensiveness.
I know how the game is played.
Ohno (and all of his disciples) were proven wrong.
For you, this is “no big deal”.
If, however, he had been proven right, his claims would be held up as great vindication and a victory for evolutionary thought.
It’s a double-standard.
So, you down-play the failures of the “junk” predictions. Ohno was just “speculating”. If he had been correct, he would have been “advancing evolutionary theory”.
I find this kind of game-playing to simply underscore the weakness of evolutionary theory. It lacks integrity. You’re willing to make claims about what functions we might find for non-coding DNA in the future.
There’s already work being done to overturn your notion that it is selfish DNA:

Not so selfish after all ? Key role of transposable elements in mammalian evolution
https://www.titech.ac.jp/english/news/2019/045702.html

This summary on recent findings was published last month:

https://evolutionnews.org/2019/12/jonathan-wells-was-right-noncoding-dna-continues-to-show-function/
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Bob O'H says:

January 5, 2020 at 3:38 pm

SA –

Ohno created the term Junk DNA because he claimed that non-coding DNA had virtually no function.

If you read the paper I linked to, you would see that he was actually suggesting functions for it.

In comment 22 Jawa asked “Why don’t we see more ID objectors in this discussion?” My response was to point out it’s not worth it. I think you’ve proven my point very well: unlike you, I actually read what he wrote, and found out that you were wrong (Ohno was actually suggesting functions for junk DNA). Your response? Ignore it, and keep repeating the same falsehoods. If you want to have a serious discussion about science, that would be great. But it means you have to be serious about it.
43

Silver Asiatic says:

January 5, 2020 at 6:25 pm

Bob

Your response? Ignore it, and keep repeating the same falsehoods.

I pointed out that you were making claims about what future discoveries of function in non-coding DNA would mean (“no big deal”), at the same time while you don’t know what NC-DNA is.
Ohno’s claim about Junk DNA was proven wrong, and it was not his suggestion that it might have some function.

unlike you, I actually read what he wrote, and found out that you were wrong

I noticed that. You talked about what the early theorists about Junk DNA said before you had read Ohno’s paper. Then you read it this week, searching for a “gotcha” as when he said it might have some function. So, you weren’t informed about it before now.

If you think you’ve scored enough points for evolution to win this battle, then you shouldn’t have a need to post here any more. But I think you’re going to find increasing challenges to your theory, and such things do continue to be a big deal.
44

Bob O'H says:

January 6, 2020 at 2:31 am

I pointed out that you were making claims about what future discoveries of function in non-coding DNA would mean (“no big deal”), at the same time while you don’t know what NC-DNA is.

But we do know what most of it is! There’s even a wikipedia page on them.

Ohno’s claim about Junk DNA was proven wrong, and it was not his suggestion that it might have some function.

Read the paper and stop repeating falsehoods. It was his suggestion that junk DNA had a function. And FWIW, he was actually not totally wrong: some non-coding DNA is indeed pseudo-genes. I’m not sure if his spacer theory has stood up, but I haven’t checked.
45

Silver Asiatic says:

January 6, 2020 at 9:33 am

Bob

Read the paper and stop repeating falsehoods. It was his suggestion that junk DNA had a function. And FWIW, he was actually not totally wrong: some non-coding DNA is indeed pseudo-genes. I’m not sure if his spacer theory has stood up, but I haven’t checked.

I believe you are trying to say that evolutionists never made false predictions about Junk DNA. That it was known and predicted that non-coding DNA would have the functions we now know it does, right? The term “Junk DNA” was never meant to signify “the remains of nature’s experiments that failed” like “fossil remains of extinct species” and there never was a challenge to understand why non-coding sequences were conserved?

“a DNA base sequence in which all sorts of mutational changes are permissible is obviously not contributing to the well-being of an organism, and for this very reason, it has no function” (Ohno 1973)

Regarding the spacer theory, in the item from Evolution News I posted they mention it.
46

Bob O'H says:

January 6, 2020 at 10:31 am

Sa

I believe you are trying to say that evolutionists never made false predictions about Junk DNA. That it was known and predicted that non-coding DNA would have the functions we now know it does, right?

No, I’m certainly not saying that. It was certainly predicted by Ohno himself that junk DNA would have a function, but certainly wasn’t “known” when he made the prediction. His prediction was not entirely wrong: some junk DNA is pseudo-genes, although most isn’t.
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PaV says:

January 8, 2020 at 10:17 pm

Bob O’H:

I just did a Google search: https://www.cell.com/trends/genetics/pdf/S0168-9525(17)30112-9.pdf

The first sentence of, I presume, the abstract ( I don’t have access):

Transposable elements are powerful drivers of adaptive genome evolution in plants and in symbiotic microbes, and contribute to their coevolution.

And here’s something from 1998: https://www.eurekalert.org/pub_releases/1998-02/UoG-TEMH-090298.php

The title of the article: “Transposable Elements May Have Had A Major Role In The Evolution Of Higher Organisms.”
48

Bob O'H says:

January 9, 2020 at 5:26 am

PaV – thank you for giving a link to another paper that doesn’t support your claim “that transposable elements … is [sic] the real driver of evolution”. Yes, they affect evolution, and I don’t think many people would object to the claim that they have a major effect. But the drivers of evolution? That’s a different claim, and I’m still waiting for you to provide the evidence.

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