tag:blogger.com,1999:blog-37148773.post9073247014440009865..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: Ford Doolittle's Critique of ENCODELarry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger20125tag:blogger.com,1999:blog-37148773.post-20313020818092632742013-08-24T06:37:55.272-04:002013-08-24T06:37:55.272-04:00Has anyone on either side of this debate removed t...Has anyone on either side of this debate removed the useless 80% of the human genome and recorded what the results where?<br /><br />"Ford is correct. The ENCODE leaders don't seem to be particularly knowledgeable about modern evolutionary theory."<br /><br />Why would they need to have a preconceived idea of the evolution theory to examine the function of something? Are they trying to confirm the paradigm, or find out what the genome does? This seems to me to be the problem with interpreting what is being looked at. Kind of like saying "I wouldn't have seen it if I didn't believe it."<br /><br />Anonymoushttps://www.blogger.com/profile/14209452496087005225noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-53112039000223134382013-03-15T12:39:51.152-04:002013-03-15T12:39:51.152-04:00My point about the unicellular/multicellular divid...My point about the unicellular/multicellular divide relates to a couple of mechanistic factors that may have a bearing - one is that the 'nutrition' cost is principally borne by the extra DNA in somatic cells, not by a combined somatic/germ cell, another is that generation times tend to be extended by the existence of that phase, increasing the time available for replication. <br /><br />But another is that the germ line DNA is encapsulated. There is less constraint to gather the materials for life in close contact with an unforgiving medium - the unit cost of germline DNA goes down; the soma pays for itself and then some. <br /><br />Prokaryotes are most severely constrained, as they are tiny, energetically limited, in direct molecular competition with relatives, must separate sister chromosomes by cell wall growth, etc. <br /><br />Single-celled eukaryotes are about 10,000 times bigger, with cytokinetic manipulation, multiple origins of replication, food engulfment, storage and/or a large energetic surface. This reduces the restraint on genome expansion. <br /><br />Multicellular eukaryotes can sit in their somatic cloak, indulging a life of leisure, with cellular specialisation the payoff for elaboration, and further freeloading DNA the cost. If you are indulging the cost of a soma, you can better afford a bit of surplus DNA. Unless you fly, of course.<br /><br />In tandem with this series goes an inevitable reduction in Ne, so naturally the correlation holds.<br /><br />I dunno - just being pedantic, perhaps - but I likes a mechanistic explanation meself!AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-80746371842591019532013-03-15T11:43:44.228-04:002013-03-15T11:43:44.228-04:00Uni/multicellular is not a large divide - there is...Uni/multicellular is not a large divide - there is nothing fundamentally different about unicellular eukaryotes, it's just our historic multicellular bias that creates the division. Multicellularity has developed multiple times in multiple lineages, independently. <br /><br />Most unicellular eukaryotes have large Ne, small genomes, with few TEs, and few introns. Similarly, smaller multicellular eukaryotes have more compressed genomes than mammals (but bigger than those of protists) and fewer TEs - flies are a perfect example and in their case TEs have the added bonus of being younger and more active, i.e. the old ones have been purged already. <br /><br />As I said, it's not a perfect relationship, it's not expected to be, but it exists. Georgi Marinovhttps://www.blogger.com/profile/12226357993389417752noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-31233555471446687962013-03-15T11:37:28.602-04:002013-03-15T11:37:28.602-04:00So if I now understand you correctly, are you argu...<i>So if I now understand you correctly, are you arguing that the selection coefficient of new TE insertions is always 0 so Ne does not play a role. </i><br /><br />Nope - that was my 'null hypothesis' :) I'm certainly not saying "s always = 0". I was arguing particularly on the nutritional cost assumption, and was looking for some justification of the assumption that <i>that</i> cost is sufficient for natural Ne differentials, and their effect on selective response, to provide 'the' explanation for patterns of junk. <br /><br />I granted that other mechanisms act against junk. In particular, a virulent transposon clearly does damage to genes, causes meiotic misalignments, <i>and</i> ups the genetic load at a rate potentially far in excess of that which can be absorbed by the below-threshold differentials of less active insertions. Then, of course, real and potentially large selection coefficients leap into action. No argument here. <br /><br />I'm interested in "TEs would not be so rare in organisms with very large population sizes.", however. What organisms are we talking about here? I am generally arguing for comparing like with like, so I'd hope this was not across a major divide such as pro/eukaryote or uni/multicellular. AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-30489350707925084572013-03-15T10:34:21.926-04:002013-03-15T10:34:21.926-04:00So if I now understand you correctly, are you argu...So if I now understand you correctly, are you arguing that the selection coefficient of new TE insertions is always 0 so Ne does not play a role. That's not true. It is clearly not 0 because it was, there would not be such elaborate defense mechanisms trying to prevent new insertions and TEs would not be so rare in organisms with very large population sizes. Georgi Marinovhttps://www.blogger.com/profile/12226357993389417752noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-30809986217797520302013-03-15T10:18:02.615-04:002013-03-15T10:18:02.615-04:00Georgi,
Yes, I think you may be misunderstanding ...Georgi,<br /><br />Yes, I think you may be misunderstanding me. I am recognising the argument, but questioning its force. <br /><br />For any imaginary small value of s, there is a threshold value of Ne below which selection is ineffective. The question would be: how robust is the assumption that s for junk increments is <i>generally</i> in the range that enables this relationship to have causal power? It may indeed be a factor (allowing certain assumptions about the efficiency with which real populations are stirred and 'sampled') but a dominant factor, I'm less convinced. <br /><br />The null hypothesis would be that s=0, and Ne doesn't matter. Adaptationists are criticised for assuming s is large, but here we have a similar assumption - s is nonzero and within a particular range. <br /><br />Obviously, the situation here is rather complex, because the detriment of a given increment of junk is highly contingent. s depends how much more or less efficient than <i>the rest of the population</i> it makes its bearers, and this will vary depending on how big it is and what other increments are around in the population at the time. <br /><br />I accept the approximate correlation, and the possibility that Ne may be one factor, but there are significant mechanistic factors relating to the different types of organism that themselves affect both the dynamics of junk, and Ne. It may be these, rather than probabilistic effects, that provide the causation. AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-16907228824168455802013-03-15T07:56:08.788-04:002013-03-15T07:56:08.788-04:00Allan Miller,
I am not sure if I understand you c...Allan Miller,<br /><br />I am not sure if I understand you correctly, but if I do, you are in effect arguing for the "Ne determines the strength of selection" position while claiming to oppose it. <br /><br />Yes, the mere existence of junk DNA has in terms of nutrition a very slight negative effect. That means the absolute value of the selective coefficient is very low. Accordingly, 1/4Ne >> s and it becomes an effectively neutral mutation and selection cannot get rid of it. That's the point. Georgi Marinovhttps://www.blogger.com/profile/12226357993389417752noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-31736298362376292542013-03-15T07:47:13.623-04:002013-03-15T07:47:13.623-04:00Larry/Georgi,
Correct, I should perhaps read more...Larry/Georgi,<br /><br />Correct, I should perhaps read more before pontificating. Nonetheless, the difficulty I see is in establishing that it is Ne itself that is the factor at work, rather than something of which change in Ne is an inevitable corollary. <br /><br />Multicellularity, for example. The principal cost of extra DNA is in building the soma. Such somas inevitably reduce the number of germ line cells that a given niche can support. But such somas generally pay their way in germ cell survival, with a bit to spare. Unless nutrition is severely and consistently limiting, junk-generating mutations (up to a point) may simply not be deleterious, for any Ne. For a population to become large, nutritional limitation - a significant determinant of 'detriment' - is less likely to be operational. <br /><br />I realise that nutrition is not the sole 'cost' of junk, and that other factors, such as meiotic misalignment, may come into play. Which may help explain the higher rate of transposons in asexual eukaryotes. AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-21688223041124176462013-03-14T11:59:57.705-04:002013-03-14T11:59:57.705-04:00Ameobas have one special feature, which has to be ...Ameobas have one special feature, which has to be taken into account when Ne is discussed and it is asexuality. <br /><br />Of course, nobody has sequenced those genomes and nobody will until super long-read sequencing becomes available but I would bet they're full of out-of-control transposons, probably in combination with some serious polyploidy. <br /><br />And that would be consistent with the theory. Which, BTW, does not say that Ne is the only thing that matters - all sorts of details about the biology of the species, the mutation rates and patterns, etc. do matter and it is not an absolute relationship as a result, only a general pattern: small Ne => big genomes, full of transposons, large Ne => small genomes, few transposons, fewer introns, etc.Georgi Marinovhttps://www.blogger.com/profile/12226357993389417752noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-69229241711873835902013-03-14T10:29:33.868-04:002013-03-14T10:29:33.868-04:00Not that it would make much of a difference: it is...Not that it would make much of a difference: it is >440 authors and 30+ papers vs. 10 authors and four papers and 200,000,000.00 vs. 0.00$SPARChttps://www.blogger.com/profile/09563722742249547887noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-59017710005201372292013-03-14T10:14:59.994-04:002013-03-14T10:14:59.994-04:00Nature is backpaddling. Well, kind of:
Many biolo...<a href="http://www.nature.com/news/form-and-function-1.12580" rel="nofollow">Nature is backpaddling</a>. Well, kind of:<br /><br /><i>Many biologists have called the 80% figure more a publicity stunt than a statement of scientific fact. Nevertheless, ENCODE leaders say, the data resources that they have provided have been immensely popular. So far, papers that use the data have outnumbered those that take aim at the definition of function.</i><br /><br />Currently, it is 400 authors and 30+ papers vs. four authors and four papers and 200,000,000.00 vs. 0.00$.<br /><br /><i>The debate sounds like a matter of definitional differences. But to dismiss it as semantics minimizes the importance of words and definitions, and of how they are used to engage in research and to communicate findings. ENCODE continues to collect data and to characterize what the 3.2 billion base pairs might be doing in our genome and whether that activity is important. If a better word than ‘function’ is needed to describe those activities, so be it. Suggestions on a postcard please.</i><br /><br />There is exactly one English word for most of these activities. It is real and you can measure it: <b>noise</b>.SPARChttps://www.blogger.com/profile/09563722742249547887noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-64945402820084786912013-03-14T09:17:18.421-04:002013-03-14T09:17:18.421-04:00Allan Miller says,
If you argue with N as the onl...Allan Miller says,<br /><br /><i>If you argue with N as the only variable, you have to do something to ensure that the new N is stirred with the same efficiency as the old, and typically it isn't (and in prokaryotes, the absence of mate search means that a significant vector is completely absent).</i><br /><br />I suspect that you haven't read Lynch's book. He discusses all sorts of other variables that can affect genome size. The main ones are mutation rates—especially the difference between deletions and insertions, generation times, recombination, and body size. He discusses whether these are correlated with population size and, if so, how. He also spends a lot of time on effective populations sizes and evolution in species with many subpopulations. <br /><br />In most cases, Lynch presents data to back up his ideas. Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-65151909256532127502013-03-14T08:55:33.055-04:002013-03-14T08:55:33.055-04:00Allan,
yes, I agree.Allan,<br /><br />yes, I agree.Pedro A B Pereirahttps://www.blogger.com/profile/15195139833344839287noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-16516998346373642202013-03-14T08:48:45.215-04:002013-03-14T08:48:45.215-04:00Allen Miller asks,
All one would need to do to el...Allen Miller asks,<br /><br /><i>All one would need to do to eliminate the junk in a genome is to make the population bigger? </i><br /><br />That doesn't necessarily follow but it does explain why most single-cell eukaryotes have genomes that are much smaller than those of multicellular species. Yeast (a fungus), for example, has a genome that's the same size as those in some bacteria. <br /> <br />(Note to nitpickers: I'm aware of amoeba genomes.)Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-59518739290225862202013-03-14T07:31:51.208-04:002013-03-14T07:31:51.208-04:00@Pedro,
Yes, I'd agree energetics is signific...@Pedro,<br /><br />Yes, I'd agree energetics is significant, but also basic 'nutrition' - one has to get the building blocks for all this surplus, and consumption is far more productive than absorption. As far as multicellulars go, I think their main cost is that multicellular body, and unless nutrition is severely limiting in general, the cost of being-multicellular-with-junk imposes a negligible increase.AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-13917142949910980492013-03-14T07:16:00.310-04:002013-03-14T07:16:00.310-04:00I don't find it convincing. All one would need...I don't find it convincing. All one would need to do to eliminate the junk in a genome is to make the population bigger? <br /><br />It is true that scaling up a population's number will render elimination of deleterious alleles more likely, but there are a couple of unproven assumptions in the most naive model. Do we know, for instance, what the selective coefficient of N bits of junk 'typically' is? It would have to be in a particular band to ensure that it could not be eliminated by a population of N individuals, but could be by a population a couple of orders of magnitude higher. Do we know that it is? There is also the issue of scaling. If you argue with N as the only variable, you have to do something to ensure that the new N is stirred with the same efficiency as the old, and typically it isn't (and in prokaryotes, the absence of mate search means that a significant vector is completely absent).<br /><br /> <i>The explanation of junk DNA has nothing to do with adaptive lanscapes.That's the whole point of nonadaptive evolution of complexity.</i><br /><br />There is nothing to say an adaptive landscape cannot be flat! As far as 'surplus' DNA is concerned, prokaryotes are on peaks. For eukaryotes, the landscape is much flatter - <i>then</i> population size may start to exert an effect. But there are many more potent mechanistic biases than that.AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-14006928417415187122013-03-14T06:48:06.848-04:002013-03-14T06:48:06.848-04:00I agree. Population size is probably not a good ex...I agree. Population size is probably not a good explanation for the prokaryote/eukaryote differences in C-value. I think it's mostly energetics; eukaryotes have a substantial surplus of energy due to mithocondria that prokaryotes don't and that enables the former to "ignore" to a certain extent the energy cost in replicating "junk". Energetic surplus is very probably the reason why eukaryotic cells achieved the level of complexity and multicellular cell specialization they have.<br /><br />I do think, however, that population size is certainly important in fixation of neutral or quasi-neutral mutations, regardless of the organisms being clonal or not. But that probably has nothing to do with C-values anyway. Pedro A B Pereirahttps://www.blogger.com/profile/15195139833344839287noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-52414768035779303442013-03-14T06:46:39.355-04:002013-03-14T06:46:39.355-04:00Lynch's point is that the small population siz...Lynch's point is that the small population sizes of SOME eukaryotes makes it impossible to eliminate slightly deleterious alleles and this is an adequate explanation of junk DNA (and other things).<br /><br />The explanation of junk DNA has nothing to do with adaptive lanscapes.That's the whole point of nonadaptive evolution of complexity.Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-48001027881429249462013-03-14T05:22:59.414-04:002013-03-14T05:22:59.414-04:00Lynch is widely quoted these days, but I find myse...Lynch is widely quoted these days, but I find myself sceptical of the primacy of population size as a significant driver of the C-value differential between eukaryotes and prokaryotes. What does 'population size' even mean in a mixed collection of clonal organisms? The individual bacterium has severe <i>local</i> constraints, and they arise from its means of making a living, not least of which are bounding within a size-limiting energy-generating outer membrane and being surrounded by cousins. <br /><br />Endosymbionts, relaxation of nutritional limits, cytoskeletons, multiple origins and sex are, IMO, much more significant than Ne with respect to the adaptive landscape traversed by the respective organisms wrt junk.AllanMillerhttps://www.blogger.com/profile/05955231828424156641noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-35693461105771892502013-03-13T19:27:42.648-04:002013-03-13T19:27:42.648-04:00I always liked Ford Doolittle's work. He's...I always liked Ford Doolittle's work. He's anything but a BSer.Argonhttps://www.blogger.com/profile/01145963627461927650noreply@blogger.com