tag:blogger.com,1999:blog-37148773.post2388710932155175719..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: Different kinds of pseudogenes - are they really pseudogenes?Larry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger18125tag:blogger.com,1999:blog-37148773.post-46857711563108995962015-11-19T12:30:20.291-05:002015-11-19T12:30:20.291-05:00I hope we are distinguishing between "gene pr...I hope we are distinguishing between "gene prediction" and "gene annotation"<br /><br />Unless I am sorely mistaken, the former GENERALLY does not include UTRs where the latter GENERALLY does.<br /><br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-79043422466573900532015-11-19T11:20:40.493-05:002015-11-19T11:20:40.493-05:00Thanks Larry, you're right. I misremembered ou...Thanks Larry, you're right. I misremembered out of the contrast with gene annotations in prokaryotes.<br /><br />SRM, while you're right that it would be easier to think of regulatory sites in bacteria as part of the gene, annotations in bacteria start with the first codon, end with the stop codon. (However, some regulatory sites are far, far away, like in eukaryotes, requiring bending of the DNA for several regulatory proteins to touch each other, etc.)Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-4364627808905101932015-11-19T10:36:55.416-05:002015-11-19T10:36:55.416-05:00Gene nomenclature can be problematic and practice ...Gene nomenclature can be problematic and practice still remains inconsistent depending on field of expertise.<br /><br />From an interesting paper: <br /><br />Developing a community-based genetic nomenclature for anole lizards - Kenro Kusumi , Rob J Kulathinal et al <br /><br />The salient quote:<br /><br />“Gene expression <br />Following gene duplication events, divergence of regulatory control regions can lead to differentiation in tissue specificity and timing of gene expression in paralogous genes. These regulatory regions are considered part of the gene being compared, but it is not straightforward to assign a score to this divergence. Genes that appear to be orthologous by the measures above can still display strikingly different gene expression, raising the question of whether the regulatory gene functionality has diverged in an opposing fashion to that of the protein coding sequence.”<br /><br />http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248570/<br /><br />Consensus on a common definition for “gene” remains somewhat elusive.<br /><br />Continuing on the subject of orthologous relationships, I cite a passage from HUGO that could prove relevant to this continuing series.<br /><br />“6.5 Pseudogenes<br /><br />Pseudogenes are sequences that are generally untranscribed and untranslated and which have high homology to identified genes. However, it has recently been shown that in different organisms or tissues functional activation may occur. Therefore, the previous policy of assigning the gene symbol of the structural gene followed by "P" and a number will only be approved on a case by case basis. In future, pseudogenes will usually be assigned the next number in the relevant symbol series, suffixed by a "P" for pseudogene (or "PS" in the specific cases) if requested e.g. OR5B12P "olfactory receptor, family 5, subfamily B, member 12 pseudogene". However, the designation "pseudogene" will remain in the gene name.”<br /><br />http://www.genenames.org/about/guidelines#homologies<br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-24610647626023143232015-11-19T08:37:00.044-05:002015-11-19T08:37:00.044-05:00photosynthesis says,
People annotating genes in e...photosynthesis says,<br /><br /><i>People annotating genes in eukaryotes tend to consider regulatory regions as part of the gene.</i><br /><br />That's not correct. Here's the GenBank entry for one of my favorite genes, <a href="http://www.ncbi.nlm.nih.gov/nuccore/NC_000009.12?report=genbank&from=125234848&to=125241387&strand=true" rel="nofollow">HSPA5</a> on human Chromosome 9.<br /><br />Here's the <a href="http://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=3309" rel="nofollow">RefSeq</a> entry for the same gene.<br /><br />And here's the UCSC Genome Browser entry for <a href="http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9%3A125234853-125241330&hgsid=454203875_MqC3q5fylvhWTvAl2CavOAi7BxPH" rel="nofollow">HSPA5</a> <br /><br />You can see that in all three cases the gene is defined from the transcription start site to the transcription termination site. In other words, the "gene" is the DNA that's transcribed. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-48493034053641765302015-11-19T07:16:54.401-05:002015-11-19T07:16:54.401-05:00photosynthesis, in your first paragraph I think yo...photosynthesis, in your first paragraph I think you have the situations reversed. It is generally much easier to conceive as regulatory regions as part of the gene in bacteria as they are generally more compact and contiguous with the transcribed region than they are in eukaryotes (caveats and qualifications notwithstanding).SRMhttps://www.blogger.com/profile/07299706694667706149noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-54396881000901069692015-11-18T22:06:54.151-05:002015-11-18T22:06:54.151-05:00People annotating genes in eukaryotes tend to cons...People annotating genes in eukaryotes tend to consider regulatory regions as part of the gene. That must make it quite difficult when dealing with less characterized genes. People annotating microbes don't consider regulatory regions as part of the genes.<br /><br />But orthology is not inferred based on whether the gene includes regulatory regions or not. Orthology is most often inferred from protein sequences (if the gene is a coding gene), and on whether the inferred phylogenies for the genes correspond with inferred phylogenies of the species where the genes reside.<br /><br />Sure, lots of complications, but that'll work for now.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-41649444596197847732015-11-18T21:24:13.455-05:002015-11-18T21:24:13.455-05:00@ Professor Moran
“Which of my statements do you ...@ Professor Moran<br /><br />“Which of my statements do you disagree with and why?”<br /><br />No disagreement really. You are citing a quick and fast catechism that is still current. I just find current orthodoxy often inconsistent; as when the inference of gene orthology across lineages, nontranscribed "regulatory regions" are often considered part of “the gene” being compared.<br /><br />The notion of gene has been defined and redefined quite a bit since William Bateson and Wilhelm Johannsen first coined the phrase. Perhaps this particular item of vocabulary has outlived its purpose and deserves to be jettisoned given archaic notions can cause undergraduate students much confusion. For example, “How are some alleles dominant and others recessive? What are the molecular mechanisms?” That question comes up every year, and answering can be problematic given “dominance” can be either “cis-dominant” or “trans-dominant”. Both are unquestionably heritable i.e.“genetic” phenomena. However, the latter is clearly the result of a “gene product” as you would define it, but the former really isn’t. <br /><br />If every gene is ultimately pleiotropic and if every trait is multigenic, then really what is “a” gene, especially when “a” given phenotype may be the result of a great many interactions from a variety of “loci”. I am intrigued with Keller’s and Harel’s suggestion of “dene”, connoting any DNA sequence that plays a role in the cell. Alright, passingly intrigued, I won’t hold my breath. <br /><br />I found this paper intriguing: <br /><br />“Thus, in a modern view of the gene and its function it is much more open and complex. It does not longer exist one true and general description;[sic] instead it takes different meaning for different scientists.”<br /><br />http://link.springer.com/article/10.1007%2Fs11191-006-9064-4<br /><br />No big deal, I think we agree more than we disagree. I just wanted to clarify and realize that I may have done just the contrary. I concede that such considerations perhaps constitute an unnecessary distraction from this interesting blog. I will retreat back into lurk-mode.<br />anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-75939799440129860232015-11-18T19:47:55.129-05:002015-11-18T19:47:55.129-05:00So now Joe appears to be saying that the claim in ...So now Joe appears to be saying that the claim in that 2003 paper is generally false. Since it's paywalled I can't check.John Harshmanhttps://www.blogger.com/profile/06705501480675917237noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-54083240349265322542015-11-18T18:56:59.107-05:002015-11-18T18:56:59.107-05:00BTW, are you prepared to identify yourself and mak...BTW, are you prepared to identify yourself and make a bet?Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-27784809534363403952015-11-18T18:56:08.088-05:002015-11-18T18:56:08.088-05:00Speaking of mindless .... if you don't have an...Speaking of mindless .... if you don't have anything to contribute other than whining about your lack of knowledge then don't say anything at all. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-36444759668768747712015-11-18T17:40:43.203-05:002015-11-18T17:40:43.203-05:00Quite early on in the pseudogene literature people...Quite early on in the pseudogene literature people developed methods for confirming that a gene was a nonexpressed pseudogene, based on rates of substitution at 1st, 2nd, and 3rd codon positions becoming the same.<br /><br />Here is a more recent paper on some of these issues:<br /><br />http://mbe.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11752196Joe Felsensteinhttps://www.blogger.com/profile/06359126552631140000noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-86087041789324848622015-11-18T17:18:31.900-05:002015-11-18T17:18:31.900-05:00I find evolution according to the modern evolution...I find evolution according to<b> the modern evolutionary theory by knowledgeable scientists approved by Larry Moran</b> quite interesting and entertaining.<br /> <br />It (mindless process) "decided "to preserve 90% of useless genome in one species, and almost none in another. Most knowledgeable scientist agree on something but no evidence is yet available. Jasshttps://www.blogger.com/profile/00012083978513644307noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-58614283061424268202015-11-18T17:06:28.582-05:002015-11-18T17:06:28.582-05:00What does that paper use to support this claim?What does that paper use to support this claim?John Harshmanhttps://www.blogger.com/profile/06705501480675917237noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-46888050163434546332015-11-18T14:40:26.859-05:002015-11-18T14:40:26.859-05:00If "true" and "not true" are t...If "true" and "not true" are the only choices then it's not true. There may be a few gene-like sequences that aren't really pseudogenes because they have acquired a function but they seem to be rare.Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-61863868938614007452015-11-18T14:23:37.199-05:002015-11-18T14:23:37.199-05:00"Pseudogenes exhibit evolutionary conservatio...<i>"Pseudogenes exhibit evolutionary conservation of gene sequence, reduced nucleotide variability, excess synonymous over nonsynonymous nucleotide polymorphism, and other features that are expected in genes or DNA sequences that have functional roles."</i><br /><br />Is this true? If so, how general is it?John Harshmanhttps://www.blogger.com/profile/06705501480675917237noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-16072647935673068542015-11-18T12:52:17.270-05:002015-11-18T12:52:17.270-05:00If you had followed the link to my post on " ...If you had followed the link to my post on " What Is a Gene" you would have seen that I discussed the point about regulatory sequences. Which of my statements do you disagree with and why?Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-79769115311658512392015-11-18T12:14:22.264-05:002015-11-18T12:14:22.264-05:00There are even some well-respected evolutionary bi...<i>There are even some well-respected evolutionary biogists who question the functionality of "pseudogenes."</i><br /><br /><i>Insist</i> on their functionality, right?<br /><br />Thanks for this new series. Very interesting!Piotr Gąsiorowskihttps://www.blogger.com/profile/06339278493073512102noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-87693014493558774432015-11-18T11:23:21.769-05:002015-11-18T11:23:21.769-05:00Now this particular blog is interesting! I do hav...Now this particular blog is interesting! I do have one question regarding the definition of "gene" before continuing with "pseudogene":<br /><br />When inferring gene orthology across lineages, should nontranscribed "regulatory regions" be considered part of “the gene” being compared? Of course, you recognize where I am heading with this, given current practice to that question already affirms the affirmative answer. And no; I am no champion of ENCODE.<br /><br />I am hoping for a civil exchange, this time.anonymoushttps://www.blogger.com/profile/06178384393256601953noreply@blogger.com