tag:blogger.com,1999:blog-37148773.post236083816387637624..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: Using conservation to determine whether splice variants are functionalLarry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger14125tag:blogger.com,1999:blog-37148773.post-20135503594269040882016-12-29T11:29:52.694-05:002016-12-29T11:29:52.694-05:00"Indeed, I cannot think of any experiment tha..."Indeed, I cannot think of any experiment that can conclusively declare a DNA segment to be mere “noise”."<br /><br />What about the experiment where several presumed "noise" DNA segments were removed and the mice produced with the modified DNA lived just fine? What about the professor who had his students sequence their own DNA in a region with several small introns and found that some had those introns and some didn't, yet they were all healthy?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-87641602012167121762016-12-29T11:00:56.775-05:002016-12-29T11:00:56.775-05:00The accusation that comparative genomics uses circ...<i>The accusation that comparative genomics uses circular logic to defend its functionality claims should be equally applied to the “noise” dogma that demands conservation for function.</i><br /><br />Any logically true statement is a logical tautology and is thus subject to the accusation that it is "circular." 2+2=4 is such a tautology or "circular" statement. The fact that functional sequences change less quickly than neutral or deleterious ones is self-evident, and also equally as true, tautological, and "circular" as 2+2=4.<br /><br />Besides lutesuite's apt citation of onions, there is also the GULOP pseudogene. There's your experiment, performed for you by Nature.judmarchttps://www.blogger.com/profile/03111006189037693272noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-6707505999351490282016-12-29T07:10:37.404-05:002016-12-29T07:10:37.404-05:00It seems the bar for declaring DNA as “noise” shou...<i>It seems the bar for declaring DNA as “noise” should be significantly higher than function. Indeed, I cannot think of any experiment that can conclusively declare a DNA segment to be mere “noise”.</i><br /><br />One word: Onions.Faizal Alihttps://www.blogger.com/profile/00937075798809265805noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-24784108456225337512016-12-29T06:48:41.738-05:002016-12-29T06:48:41.738-05:00Is it not presumptuous to demand unconserved DNA t...Is it not presumptuous to demand unconserved DNA to be assumed as “noise”, rather than “functional”? It seems the bar for declaring DNA as “noise” should be significantly higher than function. Indeed, I cannot think of any experiment that can conclusively declare a DNA segment to be mere “noise”. The accusation that comparative genomics uses circular logic to defend its functionality claims should be equally applied to the “noise” dogma that demands conservation for function.tantrevhttps://www.blogger.com/profile/02397131628997802859noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-13026676928507930782016-12-12T13:15:40.685-05:002016-12-12T13:15:40.685-05:0020-40% of NY taxis have dents in them. Therefore,...20-40% of NY taxis have dents in them. Therefore, dents must be functional. Since different taxis have different dents, this explains the difference in function between them.<br /><br />Erichttps://www.blogger.com/profile/09481645265615126897noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-6297130486797429252016-12-12T13:04:27.077-05:002016-12-12T13:04:27.077-05:00If functional DNA was immutable then we wouldn'...If functional DNA was immutable then we wouldn't see synonymous mutations.<br /><br />The fact of the matter is that deleterious mutations can occur in functional DNA which is then selected against. The removal of deleterious alleles within the population is what produces conservation of sequence.Erichttps://www.blogger.com/profile/09481645265615126897noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-91151177326141482102016-12-12T10:29:24.080-05:002016-12-12T10:29:24.080-05:00Thanks!Thanks!TheOtherJimhttps://www.blogger.com/profile/01727633779107067250noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-21957031808562513512016-12-10T16:52:40.604-05:002016-12-10T16:52:40.604-05:00Yes, that oneYes, that oneFederico Abascalhttps://www.blogger.com/profile/10122081847965890500noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-47854223162016595282016-12-10T10:42:14.051-05:002016-12-10T10:42:14.051-05:00Are you referring to the Trends in Biochemical Sci...Are you referring to the Trends in Biochemical Sciences paper, with the correct proof on-line at the moment? TheOtherJimhttps://www.blogger.com/profile/01727633779107067250noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-43924594295479587152016-12-10T10:02:52.029-05:002016-12-10T10:02:52.029-05:00"There you have it. If the splice variants we..."There you have it. If the splice variants were conserved then everyone would have looked to that as evidence of function. But if they are not conserved then that's evidence of species specificity, plasticity, and rapid evolution. Your speculation can't be falsified by comparative genomics. “<br /><br />Thankfully now we cannot only compare genomes but we can look into the patterns of genomic variation within populations. If alternative exons were species-specific innovations they should be evolving under selection on those species. We recently interrogated data from the 1000 Genomes Project and found that most alternative exons do not show such signatures of selection. Not only their ratios of non-synonymous to synonymous substitutions are close to neutral expectations but these ratios do not change with increasing allele frequencies. Hence, the evolutionary innovation “trick” cannot be invoked.<br /><br />Federico Abascalhttps://www.blogger.com/profile/10122081847965890500noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-70970684882756155942016-12-10T09:43:15.099-05:002016-12-10T09:43:15.099-05:00Conserved here means "evolving under purifyin...Conserved here means "evolving under purifying selection"; something is "conserved" if it has diverged less than expected by chance.Federico Abascalhttps://www.blogger.com/profile/10122081847965890500noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-79032363182751201942016-12-10T02:59:47.665-05:002016-12-10T02:59:47.665-05:00If conserved means a sequence is immutable, then n...If conserved means a sequence is immutable, then nothing in biology is conserved. Go deep enough in time and any gene will show some degree of divergence no matter how central it is to cellular life as we know it. Ribosomal proteins or RNA, tRNA, ribonucleotide reductase, key proteins in the electron transport chain, it doesn't matter, they <b>all</b> diverge at some point. Mikkel Rumraket Rasmussenhttps://www.blogger.com/profile/07670550711237457368noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-59079393074685722632016-12-10T01:56:56.459-05:002016-12-10T01:56:56.459-05:00"There doesn't seem to be any consensus o..."There doesn't seem to be any consensus on how to define "function" although there's general agreement on using sequence conservation as a first step."<br /><br />I'd think function should be about functionality. I guess the confusion about the definition is over my head. But defining 'conserved' is pretty easy. That just means immutable. txpiperhttps://www.blogger.com/profile/03645156881353741058noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-47761231637916651302016-12-09T20:15:35.556-05:002016-12-09T20:15:35.556-05:00+1 for my colleagues Eugene Melamud and John Moult...+1 for my colleagues Eugene Melamud and John Moult. Arlinhttps://www.blogger.com/profile/03243864308260498878noreply@blogger.com