tag:blogger.com,1999:blog-37148773.post5610019827251190615..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: Press release from the Francis Crick Institute misrepresents junk DNA Larry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger25125tag:blogger.com,1999:blog-37148773.post-37190490554749786342018-07-10T13:39:47.635-04:002018-07-10T13:39:47.635-04:00Chris Campbell: "Phylogenetic footprinting w...Chris Campbell: "Phylogenetic footprinting won't allow you to pick out an enhancer that is active at a particular time and spacial location during development, especially when said enhancer is over 500kb upstream of the gene it regulates."<br /><br />Sure it can. If a specific non-coding sequence is constrained by an essential function (e.g. transcription factor affinity) at any developmental window or in any tissue, by any target gene in the genome, it can be identified by its multi-species conservation. This is precisely why the approach works (since all tissues have the same genome to use at all stages of development). Defining the function and target promoters of the conserved elements identified in silico with wet lab approaches is the fun part that comes next.Brianhttps://www.blogger.com/profile/13530564543928677353noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-20722742174716694642018-07-07T11:21:01.896-04:002018-07-07T11:21:01.896-04:00To be more exact, promoters (or promoter regions) ...To be more exact, promoters (or promoter regions) are sites to which RNA polymerase binds to begin the process of transcription. Promoter regions may also include one or more transcription factor binding sites where some of these TFs may be activators and some may be repressors. There can also be other nucleotide regions within promoters that do not bind TFs or RNAP but that can still influence the rate of transcription initiation.SRMhttps://www.blogger.com/profile/07299706694667706149noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-44134641688574736172018-07-04T11:44:07.457-04:002018-07-04T11:44:07.457-04:00@Brian
Phylogenetic footprinting won't allow y...@Brian<br />Phylogenetic footprinting won't allow you to pick out an enhancer that is active at a particular time and spacial location during development, especially when said enhancer is over 500kb upstream of the gene it regulates.Anonymoushttps://www.blogger.com/profile/02484186057476833733noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-2349819739807867142018-06-26T15:01:06.575-04:002018-06-26T15:01:06.575-04:00I want to thank Dr. Moran for educating me about &...I want to thank Dr. Moran for educating me about 'junk DNA'.<br />One conclusion I have come to that I feel completely certain about is this-<br /><br />The notion that 'junk DNA' comes from an 'argument from ignorance' is an ignorant argument.Anonymoushttps://www.blogger.com/profile/01987183007523742829noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-47678287006952457352018-06-25T14:22:15.062-04:002018-06-25T14:22:15.062-04:00@Chris Campbell
"Nobody ever thought enhance...@Chris Campbell<br /><br />"Nobody ever thought enhancers were functionless but for many years nobody knew how to find them either because unlike coding sequence there was no easy way to identify them. Now there is. Using concepts and techniques developed by ENCODE I might add."<br /><br />Phylogenetic footprinting was pioneered by Webb Miller and colleagues at Penn State, and others at other institutions, in the early to mid 1990's precisely as a means to identify highly conserved non-coding sequences in gene loci that could possess regulatory function (sequenced manually from cosmid clones on P32-labeled gels back then, I might add). When tested as Larry mentioned in reporter assays, this strategy proved accurate in identifying transcriptional regulatory activities. The limitation to that point had been slow processor speeds that led to the multi-pairwise alignments taking days. An exponential trend in increased processor speed from that point on allowed this strategy to continue apace. The ENCODE project is the contemporary expansion of these pioneers' methods.<br />Brianhttps://www.blogger.com/profile/13530564543928677353noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-31946327902435372352018-06-25T09:55:32.814-04:002018-06-25T09:55:32.814-04:00Convergent Evolution of Alu & Line could to so...Convergent Evolution of Alu & Line could to some minds hint how parasitic DNA can be co-opted into functionality and that functionality could be “multifunctional”<br /><br />Regulatory & Bulk are not mutually exclusive to this way of thinking<br /><br />Just throwing that out there for the sake of argumentanonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-90301729423137354442018-06-24T20:43:12.612-04:002018-06-24T20:43:12.612-04:00And repressors.And repressors.John Harshmanhttps://www.blogger.com/profile/04478895397136729867noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-81724651489122579672018-06-24T10:06:50.315-04:002018-06-24T10:06:50.315-04:00Regarding
...Furthermore, we've had a pretty...Regarding <br /><br /><i>...Furthermore, we've had a pretty good understanding of regulatory DNA since the early 1980s. </i><br /><br />Is that perhaps somewhat too eukary-centric?<br /><br />Jacob & Monod elucidated the Lac Operon in the 60’s <br /><br />OK... polycistonic operons do not occur in Eukaryotes, but just the same...anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-77601346188569850572018-06-24T06:52:38.152-04:002018-06-24T06:52:38.152-04:00@Chris Campbell
By the end of the 1960s it was ob...@Chris Campbell<br /><br />By the end of the 1960s it was obvious that many genomes were much larger than necessary to contain the expected number of genes. There was much speculation about the possible function of this excess DNA. It soon became apparent that much of it was repetitive DNA and that the sizes of genomes in very similar species could vary by a factor of ten. <br /><br />When these facts were combined with Neutral Theory and genetic load arguments, it was reasonable to conclude that much of the “excess” DNA had no function. It was junk.<br /><br />My point is that there was never a time when experts simply called all of the excess DNA junk just because they didn’t know what it’s function was. They had good reasons for believing that it didn’t have a function. The concept of junk DNA was never an argument from ignorance in spite of what it’s opponents would like you to believe. <br /><br />Today we have lots of data that allow experts to infer that 90% of our genome is junk. They can identify function for about 5% of the genome. As you point out, there’s lots of conserved DNA of unknown function. Nobody thinks that fraction has to be junk. Furthermore, there’s probably lots of nonconserved DNA that will turn out to have a function. Nobody is saying that it all has to be useless junk. They are simply saying that there’s an upper limit to the amount of our genome that can be functional and that limit is less than 10%.<br /><br />This is why papers that discover a function for some new bit of DNA are not surprising to junk DNA proponents. The do not refute the claim that 90% of our genome is junk. It’s extremely annoying when these papers are promoted as evidence that most of our genome is functional. It’s extremely annoying when otherwise intelligent scientists make such a silly argument. I assume they are doing it because they don’t understand the evidence for junk DNA. I assume they don’t believe that most of our genome is junk so they see their data as conformation of their (uninformed) bias. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-36895362435264816822018-06-23T15:12:17.954-04:002018-06-23T15:12:17.954-04:00Larry, as often happens I think I expressed myself...Larry, as often happens I think I expressed myself poorly. I assume (and if I'm wrong please correct me) that when you say no one ever said that DNA of unknown function was junk, you are saying that function can be inferred to exist even if the function itself is unknown if the DNA sequence in question has been evolutionarily conserved. What you're (and presumably the other experts are) referring to as junk DNA is DNA for which function can't be inferred because the primary sequence is poorly evolutionarily conserved. Have I got that right?Anonymoushttps://www.blogger.com/profile/02484186057476833733noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-72225284900532369912018-06-23T09:04:07.099-04:002018-06-23T09:04:07.099-04:00@Chris Campbell
You would be hard-pressed to find...@Chris Campbell<br /><br />You would be hard-pressed to find any experts who ever said that DNA of unknown function was junk. <br /><br />Enhancers and other regulatory sequences were not only found but extensively analyzed in the 1970s and 1980s. My own lab did a lot a promoter bashing in the 1980s to identify regulatory elements. There were approximately 3000 other labs doing the same thing. :-)<br /><br />The standard technique developed in the 1980s was to put a bit of DNA in front of a reporter gene to see if it had enhancer activity. Gonen et al. used a reported gene (hsp68) derived from a gene cloned in my lab back in 1986. <br /><br />DNase I hypersensitivity was discovered by Hal Weintraub and Mark Groudine back in 1976. They were working in the lab next door to where I got my Ph.D. Techniques to identify sites of methylation and histone modification were worked out in the 1980s and 1990s. ENCODE researchers improved these techniques and applied them to the entire genome but they did NOT discover the concept and they did not invent most of the techniques. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-28483557358381490832018-06-22T23:01:09.028-04:002018-06-22T23:01:09.028-04:00Yeah, there are two concepts, but one of them is w...Yeah, there are two concepts, but one of them is <i>wrong</i>. Guess which.John Harshmanhttps://www.blogger.com/profile/04478895397136729867noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-60191109282424857562018-06-22T16:36:28.770-04:002018-06-22T16:36:28.770-04:00I think there are two concepts of junk DNA out the...I think there are two concepts of junk DNA out there. One is DNA that lacks function and one is DNA of unknown function. Nobody ever thought enhancers were functionless but for many years nobody knew how to find them either because unlike coding sequence there was no easy way to identify them. Now there is. Using concepts and techniques developed by ENCODE I might add.Anonymoushttps://www.blogger.com/profile/02484186057476833733noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-1391199362560782102018-06-22T03:45:43.622-04:002018-06-22T03:45:43.622-04:00Yeah it's the old divide by 500.000 problem. T...Yeah it's the old <i>divide by 500.000</i> problem. Technically one single LINE1 insertion could have a function, as a promoter for a downstream gene, or it might sit downstream from a promoter and be transcribed into a functional RNA, and the entire 499.999 rest of them could be nonfunctional. But the article makes it seem as it all of them have been found to be functional. Nothing is said about whether few or all of them are functional, so it makes it seem as if it is all of them. Mikkel Rumraket Rasmussenhttps://www.blogger.com/profile/07670550711237457368noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-46905825509499718982018-06-22T03:39:20.319-04:002018-06-22T03:39:20.319-04:00Also known as promoters.Also known as <a href="https://en.wikipedia.org/wiki/Promoter_(genetics)" rel="nofollow">promoters</a>. Mikkel Rumraket Rasmussenhttps://www.blogger.com/profile/07670550711237457368noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-7764689279821307902018-06-22T00:29:05.328-04:002018-06-22T00:29:05.328-04:00This Atlantic article, The Mysterious ‘Jumping Gen...This Atlantic article, <a href="https://www.theatlantic.com/science/archive/2018/06/line1-jumping-gene/563354/" rel="nofollow">The Mysterious ‘Jumping Gene’ That Appears 500,000 Times in Human DNA</a>, based on <a href="https://www.nature.com/articles/nsmb.2495" rel="nofollow">a paper in Nature</a>, describes a stretch of DNA, called LINE1, which appears to be clearly both functional and junky. Sure, it does something, but it probably doesn't need half a million copies.Anonymoushttps://www.blogger.com/profile/01629559601528774936noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-36229610032403984662018-06-21T21:28:17.252-04:002018-06-21T21:28:17.252-04:00Hmmm. on the point about press releases in science...Hmmm. on the point about press releases in science or anything. Is it a intent to sensationalize the subject being covered? They would say they must stress the importance of the subject and why its covered relative to others.<br />they would deny they sensationalize . They get rewarded in the MEDIA for gaining audiences and maintaining them. YES they desire the exciting point!<br />Easily they don't reread their first impression.<br />it seems in this one of the researchers backs up the press release and so they would say DON'T blame us!<br />only a few people understand these things and the public never can weigh the issue. Creationists deal with this all the time. We deal with a public that must be shown they can understand and question concepts very easily.<br />Robert Byershttps://www.blogger.com/profile/05631863870635096770noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-28680188558759362942018-06-21T17:39:25.001-04:002018-06-21T17:39:25.001-04:00It is pretty embarrassing that some still continue...It is pretty embarrassing that some still continue to stick to the junk DNA nonsense. Doesn't the time pass for the retiree crowed?<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-58041963953407976952018-06-21T15:49:35.741-04:002018-06-21T15:49:35.741-04:00Thanks John, interesting. Yes, I've heard abo...Thanks John, interesting. Yes, I've heard about them (taught about them too! The old cytochrome-C thing in OU SD226!) I've only just realised they don't produce any RNA, so if you're looking for non-junk by checking all the RNA that emerges from the nucleus, that won't find them. Presumably you have to search upstream of whatever they affect, to find them. I guess that might sometimes be tricky.strangetrutherhttps://www.blogger.com/profile/06608525362496458458noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-78507793418180155002018-06-21T15:28:08.051-04:002018-06-21T15:28:08.051-04:00Yes, that's what transcription factor binding ...Yes, that's what transcription factor binding sites are.John Harshmanhttps://www.blogger.com/profile/04478895397136729867noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-61750559904594898512018-06-21T15:21:36.663-04:002018-06-21T15:21:36.663-04:00A thought just occurred to me. Is it possible for...A thought just occurred to me. Is it possible for a piece of DNA from which no RNA ever gets produced, to act as a "regulatory element"? Presumably it might if it acts as somewhere for the reading machinery to attach to?strangetrutherhttps://www.blogger.com/profile/06608525362496458458noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-25712478351037325262018-06-21T08:11:59.380-04:002018-06-21T08:11:59.380-04:00If the public doesn’t understand the concept of re...If the public doesn’t understand the concept of regulation and junk DNA then it’s up to scientists and science writers to correct that misunderstanding, not pander to it. This press release just contributes to more misunderstanding.Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-6558929734480765082018-06-20T22:16:00.764-04:002018-06-20T22:16:00.764-04:00“Our study highlights the important role of what s...“Our study highlights the important role of what some still refer to as ‘junk’ DNA.”<br /><br />Sorry, that’s just false. No halfway knowledgeable biologist ever considered enhancers to be junk DNA. <br /><br />Now, maybe she was misquoted. But if not, then either she doesn’t know the facts, or she knowingly made a false statement that over-exaggerates the significance of her work. qetzalhttps://www.blogger.com/profile/08413549501617197428noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-45821001876859716172018-06-20T11:48:34.753-04:002018-06-20T11:48:34.753-04:00I talk briefly with the author, she know the facts...I talk briefly with the author, she know the facts, but she under estimate the public understanding.Anonymoushttps://www.blogger.com/profile/11959064689397990103noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-89834676819544502692018-06-20T10:28:29.444-04:002018-06-20T10:28:29.444-04:00Because a lot of authors don't understand the ...Because a lot of authors don't understand the concepts?PZ Myershttps://www.blogger.com/profile/10911078800554129822noreply@blogger.com