tag:blogger.com,1999:blog-37148773.post516425394975680177..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: More confusion about the central dogma of molecular biologyLarry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger52125tag:blogger.com,1999:blog-37148773.post-70457775432079042512015-07-30T16:32:37.142-04:002015-07-30T16:32:37.142-04:00I do not understand why we need to redefine and je...I do not understand why we need to redefine and jettison the term "gene", just because there is no one-to-one (or even many-to-one or one-to-many) correspondence between genes and traits. And thus I do not see the relevance of your examples. Could you explain?<br /><br />Unless of course you've already left in a huff. If that's too soon, make it a minute and a huff. Or you could leave in a taxi.John Harshmanhttps://www.blogger.com/profile/06705501480675917237noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-44775551875584286062015-07-30T11:16:40.150-04:002015-07-30T11:16:40.150-04:00"I suggest in future you both may want to tre..."I suggest in future you both may want to treat passers-by with more consideration."<br /><br />I suggest in the future you, when passing by, stop presenting yourself as the Holy Soothsayer of all knowledge. You reap what you sow.nmanninghttps://www.blogger.com/profile/14767343547942014627noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-7987579543415899442015-07-30T11:11:15.250-04:002015-07-30T11:11:15.250-04:00John Harshman
regarding: ...you have conflated g...John Harshman<br /><br />regarding: <i> ...you have conflated genes and traits.</i><br /><br />Not at all; I have merely attempted to illustrate why the current usage of term "gene" is problematic. Professor Moran's invocation of a restrictive "biochemical" definition does not resolve the problem.<br /><br />My thought experiment remains unanswered: In fact, it is not possible in principle to <b>with certainty</b> predict my eye color (for example) even when provided complete OCA2 and HERC2 DNA sequence data.<br /><br />That was the whole point of the Lehner paper that you and Professor Moran persist in ignoring.<br /><br />I hope at some time in future when you finally get around to reading the the Lehner paper, you find it as exciting as I did.<br /><br />regarding: <i>"But it's not usually considered an insult."</i><br /><br />You and Professor Moran have demonstrated no little condescension. You both have attempted to "put me in my place". I have a plane to catch and better occasions to occupy my time. I suggest in future you both may want to treat passers-by with more consideration.<br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-33084790297256716902015-07-30T10:16:15.921-04:002015-07-30T10:16:15.921-04:00Your problem is that nobody was asking about "...Your problem is that nobody was asking about "traits that aren't confined to a single locus". The question was about <i>genes</i> that aren't confined to a single locus. Which shows that, as I said, you have conflated genes and traits.<br /><br />You may wish to flounce off, but all that happened here is that someone disagreed with you. Perhaps on other forums nobody does that. But it's not usually considered an insult.John Harshmanhttps://www.blogger.com/profile/06705501480675917237noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-8903891707848626212015-07-29T23:47:43.093-04:002015-07-29T23:47:43.093-04:00John Harshman
I am perfectly cognizant of the dis...John Harshman<br /><br />I am perfectly cognizant of the distinction between multigenenic aka polygenic vs. pleiotropic vs. epistatic as indicated in more than one post above.<br /><br />You are incorrect: I have in fact NOT "mentioned a number of polygenic traits" but have mentioned rather, epistasis & gene complementation which I conceded were <b>trivial </b>examples of traits "that aren't confined to a single locus".<br /><br />My initial disagreement with Professor Moran regards what I currently consider ambiguous if not downright incoherent usage of the word "gene", which brings me back to Sydney Brenner's higher order conception of "gene" as a computer subroutine. I can only suppose Sydney Brenner is also guilty of "new-age gobbledygook".<br /><br />Meanwhile, there is more to development than DNA sequences. <br /><br />Unfortunately my exchange with Professor Moran appears to have become "personal", so I really want to add nothing more.<br /><br />Other forums are more inviting and more engaging.anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-56049403694814377762015-07-29T21:27:26.638-04:002015-07-29T21:27:26.638-04:00Tages: You seem to be conflating traits with genes...Tages: You seem to be conflating traits with genes. Is the term "polygenic" at all familiar to you? You have merely mentioned a number of polygenic traits, not genes with more than one locus.John Harshmanhttps://www.blogger.com/profile/06705501480675917237noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-77890333422642218902015-07-29T20:50:16.503-04:002015-07-29T20:50:16.503-04:00Professor Moran
Your challenge: I bet you can...Professor Moran<br /><br />Your challenge: <i>I bet you can't name ten genes in the E. coli genome that aren't confined to a single locus...<br />How about humans?</i><br /><br />You will note, I specifically restricted my conjecture to eukaryotic organisms. I find it ironic that you seem to be having difficulty finding human genes that are restricted to <b> one</b> locus<br /><br />Let's focus on your first three citations, and I repeat:<br /><br />1 - two blue eyed parents can have a brown eyed child because part of the pigment making process involves <b> two </b> loci OCA2 and HERC2<br /><br />2 - Similarly, a Bombay Type O father and an A mother can have an AB child.<br /><br />3 - Similarly, an XY genotype can be female for a variety of complicated reasons involving more than one loci.<br /><br />All of these examples are admitedly trivial! William Bateson himself coined the phrase "epistasis" and as far back as the 1940's, George Beadle and Edward Tatum characterized gene complementation in <b> Fungi</b>.<br /><br />Clearly you either have not read Lehner's paper or you have failed to understand its implications wrt the random/statistical variation exhibited by the multiple genetic components which all contribute to a very unpredictable "phenotype" <br /><br />Meanwhile you have ignored my challenge regarding Professor Doolittle's expansion of the term "gene" in his seminal paper challenging ENCODE.<br /><br />I never "quibbled" but clearly we are both wasting our time.<br /><br /><br /><br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-60852267783876986002015-07-29T18:09:22.199-04:002015-07-29T18:09:22.199-04:00Tages Haruspex says,
We will need to resume this...Tages Haruspex says,<br /><br /><i> We will need to resume this discussion on a later date.</i><br /><br />I don't think so. Your ideas are so confusing that it hurts my brain trying to imagine what you could possible mean that makes any sense. <br /><br />I think you're just quibbling as in your response to my suggestion that there are genes that determine the color of your eyes or your blood type. That's just childish. <br /><br />If you really want to continue this conversation then give me some real examples of your kind of genes. You should not have any trouble finding ten in <i>E. coli</i>, yeast, and humans. <br />Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-15148417494588938982015-07-29T16:15:13.550-04:002015-07-29T16:15:13.550-04:00Professor Moran
We just crossed posts.
I am pack...Professor Moran<br /><br />We just crossed posts.<br /><br />I am packing for a conference and will be absent for the interim. We will need to resume this discussion on a later date.<br /><br />au revoiranonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-1756103128126346842015-07-29T16:11:23.393-04:002015-07-29T16:11:23.393-04:00Professor Moran
Funny you should mention those th...Professor Moran<br /><br />Funny you should mention those three. <br /><br />All three exhibit non-Mendelian inheritance on occasion.<br /><br />1 - Bombay blood group<br />2 - complete androgen insensitivity syndrome <br />3 - HERC2 blue eyed children<br /><br />Only recently have we tentatively been able to predict from sequence evidence correct phenotypes although I am still not too sure we can yet say that with 100 % certainty.<br /><br />In any case, I already conceded there do exist a <b> minority </b> of "loci" that behave in Mendelian fashion. <br /><br />The majority of genetics is best understood as the random/statistical variation exhibited by a cascade of multigenic and pleiotropic components which all contribute to a "phenotype" that remain quite refractory to prediction. Single locus genetics remains the exception and not the rule.<br /><br />Please read that paper. I have no desire to recapitulate Mayr's debate with Haldane regarding "beanbag genetics".<br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-46385165980504203452015-07-29T16:08:19.732-04:002015-07-29T16:08:19.732-04:00Tages Haruspex says
you seem to be insisting on a...Tages Haruspex says<br /><br /><i>you seem to be insisting on a common outdated presumption that gene must still somehow imply a single "locus".<br /><br />That may be true for a minority of genes that can be mapped like Morgan's and Sturtevant's "beads on a string" but the majority of "genes" (if we must persist in using that term for pragmatic considerations) belies a far more complex narrative.</i><br /><br />Really? I bet you can't name ten genes in the <i>E. coli</i> genome that aren't confined to a single locus. How about yeast? Can you name ten yeast genes that conflict with my preferred definition?<br /><br />How about humans? Name ten well-characterized human "genes" that aren't confined to a single locus. (You can count immunoglobulin genes as four of them.)Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-78840053026612384352015-07-29T15:46:36.384-04:002015-07-29T15:46:36.384-04:00Yes, of course it's possible. Send me your gen...Yes, of course it's possible. Send me your genome sequence and I'll predict whether you are male or female. I'll also have an excellent chance of predicting the color of your eyes and your blood type. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-79071682179226934892015-07-29T11:00:01.807-04:002015-07-29T11:00:01.807-04:00Professor Moran
So I did answer your question.
I...Professor Moran<br /><br />So I did answer your question.<br /><br />I notice you did not answer mine. I repeat:<br /><br /><i>A thought experiment: Is it possible, even in principle, to predict phenotype even if we could sequence and "characterize" some eukaryotic organism's genome?</i><br /><br />On the presumption, of course, there are no obvious confounding variables.anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-12709068501436590842015-07-29T10:52:31.541-04:002015-07-29T10:52:31.541-04:00Professor Moran
Regarding your assessment of the ...Professor Moran<br /><br />Regarding your assessment of the Djebali et al quotation <br /><br /><i> Not a chance. The paragraph you quoted is just new-age gobbledygook. </i><br /><br />I am surprised you would say so. I cut and pasted that endorsement by Ford Doolittle directly from his paper: <br /><b> Is junk DNA bunk? A critique of ENCODE</b> <br /><br />No differently than Djebali et al, Professor Doolittle maintains:<br /><br /><i>Minimally, gene means more than it used to mean. </i><br /><br />regarding : <i>"Have you read What Is a Gene??"</i><br /><br />I have and I repeat; you seem to be insisting on a common outdated presumption that gene must still somehow imply a single "locus".<br /><br />That may be true for a <b>minority </b>of genes that can be mapped like Morgan's and Sturtevant's "beads on a string" but the majority of "genes" (if we must persist in using that term for pragmatic considerations) belies a far more complex narrative.<br /><br />Have you read <br />http://www.nature.com/nature/journal/v480/n7376/full/nature10665.html<br />?anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-3495154003125005692015-07-29T09:50:45.540-04:002015-07-29T09:50:45.540-04:00Tages Haruspex
I am guessing, but I think you are...Tages Haruspex<br /><br /><i>I am guessing, but I think you are testing me. If we were to continue this exchange, I presume you really endorse the more subtle version of Djebali et al where "gene" comprises more than some solitary transcript.</i><br /><br />Not a chance. The paragraph you quoted is just new-age gobbledygook. <br /><br />Some genes produce more than one functional transcript. The well-studied examples of known biologically functional alternative splicing are good examples. It's difficult to capture all these exceptions in a single concise definition but that doesn't mean we have to abandon the idea of a gene altogether. <br /><br />Have you read <a href="http://sandwalk.blogspot.ca/2007/01/what-is-gene.html" rel="nofollow">What Is a Gene?</a>? Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-26101110122828594142015-07-29T09:36:57.093-04:002015-07-29T09:36:57.093-04:00Tages Haruspex asks,
What exactly do you mean by ...Tages Haruspex asks,<br /><br /><i>What exactly do you mean by "function"?<br /><br />DNA that is transcribed into any version of RNA; that directly or indirectly, actually ends up doing something useful for the cell, even in the long term, even if non-essential? </i><br /><br />That pretty much covers it. I'm not really interested in quibbling about the exact meaning of the word "function" because there's no definition of a gene that's airtight. Biology is messy but we do the best we can.<br /><br />I notice that you have not responded to my request to give us a better definition. Is that because you think the word "gene" is no longer useful in biochemistry and molecular biology? Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-60290371823492563872015-07-29T08:44:41.141-04:002015-07-29T08:44:41.141-04:00Professor Moran
Djebali et al. :
…the determinat...Professor Moran<br /><br />Djebali et al. :<br /><br /><i>…the determination of genic regions is currently defined by the cumulative lengths of the isoforms and their genetic association to phenotypic characteristics, the likely continued reduction in the lengths of intergenic regions will steadily lead to the overlap of most genes previously assumed to be distinct genetic loci. This supports and is consistent with earlier observations of a highly interleaved transcribed genome, but more importantly, prompts the reconsideration of the definition of a gene. As this is a consistent characteristic of annotated genomes, <b>we would propose that the transcript </b>be considered as the <b>basic atomic unit of inheritance.</b> Concomitantly, <b>the term gene would then denote a higher-order concept</b> intended to capture all those transcripts (eventually divorced from their genomic locations) that contribute to a given phenotypic trait.</i><br /><br />I am guessing, but I think you are testing me. If we were to continue this exchange, I presume you really endorse the more subtle version of Djebali et al where "gene" comprises more than some solitary transcript.<br /><br />Myself, I have difficulties with Djebali et al's approach. The "function" of the transcript is inherent in the DNA sequence. In other words, the DNA sequence contains information, which when mutated creates a loss of function.<br /><br />Loss of function can also arise when mutating crucial DNA sequences that are not transcribed (enhancers/insulators as one example). These DNA sequences are no less <b>hereditary</b> than DNA sequences that are transcribed and should similarly be included in "gene" as a "higher-order concept on the presumption that "Modern Genetics" ( I doubt that term will follow phrenology into history's dustbin) still has something to do with "Hereditary".<br /><br />At this point, I am betraying my own personal prejudice on how eventual agreement on common usage will ultimately play out.anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-39737861045876480172015-07-29T07:58:43.415-04:002015-07-29T07:58:43.415-04:00Professor Moran
"half a century"? Much...Professor Moran<br /><br />"half a century"? Much longer than that actually.<br /><br />Speaking of "half a century": I hope we are not repeating Ernst Mayr's debate with J.B.S. Haldane, when Mayr in 1959 suggested Haldane's approach to Population Genetics could be characterized as "beanbag genetics".<br /><br />What exactly do you mean by "function"? <br /><br />DNA that is transcribed into any version of RNA; that directly or indirectly, actually ends up doing something useful for the cell, even in the long term, even if non-essential? <br /><br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-27546686204367518942015-07-29T07:22:21.030-04:002015-07-29T07:22:21.030-04:00@Tages Haruspex
I don't understand your fixat...@Tages Haruspex<br /><br />I don't understand your fixation on "trait" and "phenotype." Genes aren't the only thing that affects phenotype. We've known that for half a century. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-58605834240404206302015-07-29T07:07:44.744-04:002015-07-29T07:07:44.744-04:00Of course I meant to place "GENETIC" in ...Of course I meant to place "GENETIC" in quotes.anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-87338541678989583392015-07-29T07:00:30.170-04:002015-07-29T07:00:30.170-04:00Professor Moran,
"Biochemical" you say?...Professor Moran,<br /><br />"Biochemical" you say?<br /><br />That could be as good a definition as any other for a term that has outlived its utility, on the understanding your version of "function" is far removed from what has been generally understood to be "trait"or "phenotype".<br /><br />That is alright. The meaning of words can also evolve, why should "gene" be any different?<br /><br />http://www.mirror.co.uk/news/uk-news/words-literally-changed-meaning-through-2173079<br /><br />I am surprised at your facile dismissal of Lehner's paper. The random/statistical variation exhibited by the multiple genetic components which all contribute to a "phenotype" should vex the apologists/accomodationists on Uncommon Descent. <br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-54690583256110418842015-07-28T21:56:26.874-04:002015-07-28T21:56:26.874-04:00Tages Haruspex asks,
Perhaps you could define &qu...Tages Haruspex asks,<br /><br /><i>Perhaps you could define "functional product" in light of this paper:</i><br /><br />No. That paper has nothing to do with the biochemical definition of a gene. I'm saying that the functional product is a transcript. <br />Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-51003679391249016982015-07-28T20:48:07.169-04:002015-07-28T20:48:07.169-04:00If pushed to the wall: I would compare a genome to...If pushed to the wall: I would compare a genome to an "operating system" and a "gene" to some sort of "subroutine" including but not limited to what you call "functional products".<br /><br />I cannot claim originality for that metaphor. Frankly it is lacking, but the best I could think of on the spur of a moment.anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-28149711713316108102015-07-28T20:42:37.905-04:002015-07-28T20:42:37.905-04:00Professor Moran
We aren't talking about gene ...Professor Moran<br /><br /><i>We aren't talking about gene expression.</i><br /><br />You are correct, I could have phrased that better.<br /><br /><i>Feel free to offer a better definition of "gene."</i><br /><br />I think you missed my point. I do not need to provide a definition for a concept I already deemed "incoherent".<br /><br />Perhaps you could define "functional product" in light of this paper:<br /><br />http://www.nature.com/nature/journal/v480/n7376/full/nature10665.html<br /><br />A simplistic Mendelian “one gene, one trait” model violates everything we know about inheritance.<br /><br />A thought experiment: Is it possible, even in principle, to predict phenotype even if we could sequence and "characterize" some eukaryotic organism's genome? anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-62952121957013122862015-07-28T19:54:29.720-04:002015-07-28T19:54:29.720-04:00Not impossible, but I suspect much, much more diff...Not impossible, but I suspect much, much more difficult than forward translation. Consistently recognizing a single amino acid within a polypeptide chain under many difference sequence contexts is a harder task than recognizing a single nucleic acid (or, even easier, a set of three) within an RNA strand. Of course, if you were working with a smaller set of highly distinct amino acids, things would be easier. Still, reading and writing at the molecular scale is much easier with nucleic acids than proteins, independent of current biological mechanisms for doing so.Davidhttps://www.blogger.com/profile/05235292977400315650noreply@blogger.com