Recently a paper appeared by Ratcliff et al. (2012) entitled “Experimental evolution of mulitcellularity” and received a fair amount of press attention, including a story in the New York Times. (http://tinyurl.com/6va4fpp ) The authors discuss their results in terms of the origin of multicellularity on earth. The senior author of the paper is Michael Travisano of the University of Minnesota, who was a student of Richard Lenski’s in the 1990s. The paper, published in PNAS, was edited by Lenski. The gist is as follows. The authors repeated three steps multiple times: 1) they grew single-celled yeast in a flask; 2) briefly centrifuged it; and 3) took a small amount from the bottom of the flask to seed a new culture. This selected for cells that sedimented faster than most. After a number of rounds of selection the cells sedimented much faster than the beginning cells. Examination showed that the fast-sedimenting cells formed clusters due to incomplete separation of replicating mother-daughter cells. The cell clusters also were 10% less fit (that’s quite an amount) than the beginning cells in the absence of the sedimentation selection. After further selection it was seen that some cells in clusters would “commit suicide” (apoptosis), which apparently made the clusters more brittle and allowed chunks to break off and form new clusters. (The beginning cells already had the ability to undergo apoptosis.)

硬件维修|系统软件教程|系统工具软件下载|电脑软件使用技巧 ...:恩腾技术圈(www.rvibo.com)旨在为广大网友分享最新的硬件维修经验，常用的系统软件教程，实用的工具软件下载，电脑windows系统下载，电脑windows系统驱动下载，电脑软硬件使用技巧等。

Literature Cited

班迪录屏下载 Bandicam(高清录制视频软件) v4.5.8.1673 ...:2021-4-9 · Bandicam(高清录制视频软件) v4.5.8.1673 汉化破解免费版(附注册机),Bandicam是一款非常给力的视频录制工具，该高清录制视频软件的优势在于对电脑配置要求低，且不会出现声音画面不同步的录 …

I never thought it would happen but, in my estimation, Richard Lenski has acquired a challenger for the title of “Best Experimental Evolutionary Scientist.” Lenski, of course, is the well-known fellow who has been growing E. coli in his lab at Michigan State for 50,000 generations in order to follow its evolutionary progress. His rival is Joseph Thornton of the University of Oregon who, by inferring the sequences of ancient proteins and then constructing (he calls it “resurrecting”) their genes in his lab, is able to characterize the properties of the ancestral proteins and discern how they may have evolved into more modern versions with different properties.

I have written appreciatively about both Lenski and Thornton before, whose work indicates clear limits to Darwinian evolution (although they themselves operate within a Darwinian framework). Thornton’s latest work is beginning to show a convergence with Lenski’s that greatly boosts our confidence that they both are on the right track. In a recent review (Behe, 2010) I pointed out that all characterized 小马出墙turbo破解 mutations that Richard Lenski has observed in his twenty-year experiment have turned out to be degradative ones — ones in which a gene or genetic control structure was either destroyed or rendered less effective. (Random mutation is superb at degrading genetic material, which sometimes is helpful to an organism.) In his latest work Thornton, too, shows evolution of a system by degradation, although he speculates that the changes were neutral rather than advantageous.

恐怖X系列破解版下载-《恐怖X系列》中文免安装版-ucbug软件站:2021-5-29 · 下载 《愤怒的高尔夫》中文免安装版1.02 GB / 20-05-28 下载 《被遗忘的方式》中文免安装版823.44 MB / 20-05-28 下载 《血色狂怒》中文免安装版882.56 MB / 20-05-28 dnf最新外挂 cf外挂 4399洛克王国 dnf免费外挂 4399赛尔号 CF透视 赛尔号 CF秒杀挂 奥拉

How did protein 3 insinuate itself into the ring? The original protein 1, present in five copies in most organisms, already had the ability to bind to itself, plus an ability to bind to one side of protein 2, plus a separate ability to bind to the opposite side of protein 2 (see Finnegan et al’s Figure 3). Thornton’s results are consistent with the idea that, by happenstance, the gene for protein 1 duplicated and spread in the population. (These events apparently were neutral, the authors think, not affecting the organism’s fitness.) Eventually one of the duplicates acquired a degradative mutation, losing the ability to bind one side of protein 2. This was not a problem because the second copy of the protein 1 gene was intact, and could bind both sides of protein 2, so a complete ring could still be formed. This also spread by neutral processes. As luck might have it, the second gene copy subsequently acquired its own degradative mutation, so that it could no longer bind the other side of protein 2. Again it’s no problem, however, because the first mutant copy of protein 1 could bind to the first side of protein 2, bind a few more copies of itself, then bind a copy of protein 3, which still had the ability to bind the other side of protein 2. So a closed, six-member ring could still be formed. This apparently also spread by neutral processes until it took over the entire kingdom of fungi.

The work of Finnegan et al (2012) strikes me as quite thorough and elegant. I have no reason to doubt that events could have unfolded that way. However, the implications of the work for unguided evolution appear very different to me then they’ve been spun in media reports. ( http://tinyurl.com/7lawgpl ) The most glaringly obvious point is that, like the results of Lenski’s work, this is evolution by degradation. All of the functional parts of the system were already in place before random mutation began to degrade them. Thus it is of no help to Darwinists, who require a mechanism that will construct new, functional systems. What’s more, unlike Lenski’s results, the mutated system of Thornton and colleagues is not even advantageous; it is neutral, according to the authors. Perhaps sensing the disappointment for Darwinism in the results, the title of the paper and news reports emphasize that the “complexity” of the system has increased. But increased complexity by itself is no help to life — rather, life requires functional complexity. One can say, if one wishes, that a congenitally blind man  teaming up with a congenitally legless man to safely move around the environment is an increase in “complexity” over a sighted, ambulatory person. But it certainly is no improvement, nor does it give the slightest clue how vision and locomotion arose.

Finnegan et al’s (2012) work intersects with several other concepts. First, their work is a perfect example of  Michael Lynch’s idea of “subfunctionalization”, where a gene with several functions duplicates, and each duplicate loses a separate function of the original. (Force et al, 1999) Again, however, the question of how the multiple functions arose in the first place is begged. Second, it intersects somewhat with the recent paper by Austin Hughes (2011) in which he proposes a non-selective mechanism of evolution abbreviated “PRM” (plasticity-relaxation-mutation), where a “plastic” organism able to survive in many environments settles down in one and loses by degradative mutation and drift the primordial plasticity. But again, where did those primordial functions come from? It seems like some notable workers are converging on the idea that the information for life was all present at the beginning, and life diversifies by losing pieces of that information. That concept is quite compatible with intelligent design. Not so much with Darwinism.

Finally, Thornton and colleagues latest work points to strong limits on the sort of neutral evolution that their own work envisions. The steps needed for the scenario proposed by  Finnegan et al (2012) are few and simple: 1) a gene duplication; 2) a point mutation; 3) a second point mutation. No event is deleterious. Each event spreads in the population by neutral drift. Notice that the two point mutations do not have to happen together. They are independent, and can happen in either order. Nonetheless, this scenario is apparently exceedingly rare. It seems to have happened a total of one (that is, 1) time in the billion years since the divergence of fungi from other eukaryotes. It happened only once in the fungi, and a total of zero times in the other eukaryotic branches of life. If the scenario were in fact as easy to achieve in nature as it is to describe in writing, we should expect it to have happened many times independently in fungi and also to have happened in all other branches of eukaryotes.

It didn’t. Thus it seems a good conclusion that such neutral scenarios are much rarer than some workers have proposed (Gray et al, 2010; Lukes et al, 2011), and that more complex neutral scenarios are unlikely to happen in the history of life.

Literature Cited

Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

Finnigan, G. C., V. Hanson-Smith, T. H. Stevens, and J. W. Thornton, 2012 Evolution of increased complexity in a molecular machine. Nature doi: 10.1038/nature10724.

Force, A., M. Lynch, F. B. Pickett, A. Amores, Y. L. Yan et al. 1999 Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151: 1531-1545.

Gray, M. W., J. Lukes, J. M. Archibald, P. J. Keeling, and W. F. Doolittle, 2010 Irremediable complexity? Science 330: 920-921.

Hughes, A. L., 2011 Evolution of adaptive phenotypic traits without positive Darwinian selection. Heredity (Edinb.) doi: 10.1038/hdy.2011.97.

Lukes, J., J. M. Archibald, P. J. Keeling, W. F. Doolittle, and M. W. Gray, 2011 How a neutral evolutionary ratchet can build cellular complexity. IUBMB Life 63: 528-537.

In the June 2011 issue of PLOS Genetics the laboratory of University of Oregon evolutionary biologist Joseph Thornton published ( 小马出墙破解版app ) “Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor”, the latest in their series of papers concerning the evolution of proteins that bind steroid hormones. (Carroll et al, 2011) In earlier laboratory work ( http://tinyurl.com/3hevjzy ) they had concluded that a particular protein, which they argued had descended from an ancestral, duplicated gene, would very likely be unable to evolve back to the original ancestral protein, even if selection favored it. (Bridgham et al, 2009) The reason is that the descendant protein had acquired a number of mutations which would have to be reversed, mutations which, the authors deduced, would confer no benefit on the intermediate protein. They used these results to argue for a molecular version of “Dollo’s Law”, which says roughly that a given forward evolutionary pathway is very unlikely to be exactly reversed.

In my comments on this interesting work ( 小马出墙破解版下载 ), I noted that there is nothing time-asymmetric about random mutation/natural selection, so that the problem they saw in reversing the steroid hormone receptor evolution did not have to be in the past — it could just as easily have been in the future. The reason is that natural selection hones a protein to its present job, with regard to neither future use nor past function. Thus, based on Thornton’s work, one would not in general expect a protein that had been selected for one function to be easily modified by RM/NS to another function. I have decided to call this the Time-Symmetric Dollo’s Law, or “TSDL”.

But if there is such a thing as a TSDL, did the forward evolution of the steroid-hormone protein-receptor manage to avoid it? That question had not yet been addressed. Was the protein lucky this time, and encountered no obstacles to its evolution from the ancestral state to the modern state? If so, then maybe TSDL is occasionally an obstacle, but not so often as to rule out modest Darwinian evolution of proteins (as I had thought before reading Thornton’s earlier work).

Well, thanks to the Thornton group’s new work ( 小马出墙破解版下载 ), we can now see that there are indeed obstacles to the forward evolution of the ancestral protein. The group was interested in which of the many sequence changes between the ancestral and derived-modern protein were important to its change in activity, which consisted mostly of a considerable weakening of the protein’s ability to bind its steroid ligands. They narrowed the candidates down to two amino acid positions, residues 43 and 116. Each of the changes at those sites decreased binding by over a hundred-fold. However, when the researchers combined both mutations into a single protein, as occurs in the modern protein, binding was not only decreased — it was for all intents and purposes abolished. Upon further research the group showed that a third mutation, at position 71, was necessary to ameliorate the effects of the combination of the other two mutations, bringing them back to hundreds-fold loss of function rather than essentially-complete loss of function.

Carroll et al (2011) conjecture that the mutation at position 71 occurred before the other two mutations, but that it had no effect on the activity of the ancestral protein. So let us count the ways, then, in which “fortune” favored the evolution of the modern protein. First, an ancestral gene duplicated, which would usually be considered a neutral event. Thus it would not have the assistance of natural selection to help it spread in the population. Next, it avoided hundreds of possible mutations which would have rendered the duplicated gene inactive. Third, it acquired a neutral mutation at position 71. Thus, again, this mutation would have to spread by drift, without the aid of natural selection. Once more, the still-neutral gene manages to avoid all of the possible mutations that would have inactivated it. Next, it acquires the correct mutation (either at position 43 or 116) which finally differentiates it from its parent gene — by reducing its activity a hundred-fold! Finally, somehow the wimpy, mutated gene (putatively) confers upon the lucky organism some likely-quite-weak selective advantage.

The need for passage through multiple neutral steps plus the avoidance of multiple likely-deleterious steps to produce a protein that has lost 99% of its activity is not a ringing example of the power of Darwinian processes. Rather, as mentioned above, it shows the strength of TSDL. Darwinian selection will fit a protein to its current task as tightly as it can. In the process, it makes it extremely difficult to adapt to a new task or revert to an old task by random mutation plus selection.

Dollo’s law holds going forward as well as backward. We can state the experimentally based law simply: “Any evolutionary pathway from one functional state to another is unlikely to be traversed by random mutation and natural selection. The more the functional states differ, the much-less likely that a traversable pathway exists.”

1. Carroll, S. M., E. A. Ortlund, and J. W. Thornton, 2011 Mechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor. PloS. Genet. 7: e1002117.

2. Bridgham, J. T., E. A. Ortlund, and J. W. Thornton, 2009 An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461: 515-519.

An intriguing ‘hypothesis’ paper entitled “How a neutral evolutionary ratchet can build cellular complexity” (1), where the authors speculate about a possible solution to a possible problem, recently appeared in the journalIUBMB Life. It is an expanded version of a short essay called “Irremediable Complexity?” (2) published last year in 小马出墙破解版app. The authors of the manuscripts include the prominent evolutionary biologist W. Ford Doolittle.

The gist of the paper is this. The authors think that over evolutionary time, neutral processes would tend to “complexify” the cell. They call that theoretical process “constructive neutral evolution” (CNE). In an amusing analogy they liken cells in this respect to human institutions:

Organisms, like human institutions, will become ever more ”bureaucratic,” in the sense of needlessly onerous and complex, if we see complexity as related to the number of necessarily interacting parts required to perform a function, as did Darwin. Once established, such complexity can be maintained by negative selection: the point of CNE is that complexity was not created by positive selection. (1)

松果倾诉最新版下载- 全方位下载:2021-6-28 · 松果倾诉app是一款手机情感交流服务软件，生活遇到的婚姻、家庭、情感、事业、职场、亲子、朋友间的各种压力和痛苦，都可以在松果倾诉得到很好的开解和指导，把你想说的通过语音或文字形式告诉我们，让你从情绪低谷从新走出

The possible problem the authors are trying to address is that they think many systems in the cell are needlessly complex. For example, the spliceosome, which “splices” some RNAs (cuts a piece out of the middle of a longer RNA and stitches the remaining pieces together), is a huge conglomerate containing “five small RNAs (snRNAs) and >300 proteins, which must be assembled de novo and then disassembled at each of the many introns interrupting the typical nascent mRNA.” (1) What’s more, some RNAs don’t need the spliceosome — they can splice themselves, without any assistance from proteins. So why use such an ungainly assemblage if a simpler system would do?

The authors think the evolution of such a complex is well beyond the powers of positive natural selection: “Even Darwin might be reluctant to advance a claim that eukaryotic spliceosomal introns remove themselves more efficiently or accurately from mRNAs than did their self-splicing group II antecedents, or that they achieved this by ‘numerous, successive, slight modifications’ each driven by selection to this end.” (1)

Well, I can certainly agree with them about the unlikelihood of Darwinian processes putting together something as complex as the spliceosome. However, leaving aside the few RNAs involved in the splicesome, I think their hypothesis of CNE as the cause for the interaction of hundreds of proteins — or even a handful — is quite implausible. (An essay skeptical of large claims for CNE, written from a Darwinian-selectionist viewpoint, has appeared recently (3) along with a response from the authors (4)).

The authors rationale for how a protein drifts into becoming part of a larger complex is illustrated by Figure 1 of their recent paper (similar to the single figure in theirScience essay). A hypothetical “Protein A” is imagined to be working just fine on its own, when hypothetical “Protein B” serendipitously mutates to bind to it. This interaction, postulate the authors, is neutral, neither helping nor harming the ability of Protein A to do its job. Over the generations Protein A eventually suffers a mutation which would have decreased or eliminated its activity. However, because of the fact that Protein B is bound to it, the mutation does not harm the activity of Protein A. This is still envisioned to be a neutral interaction by the authors, and organisms containing the Protein A-Protein B complex drift to fixation in the population. Then other mutations come along, co-adapting the structures of Protein A and Protein B to each other. At this point the AB complex is necessary for the activity of Protein A. Repeat this process several hundred more times with other proteins, and you’ve built up a protein aggregate with complexity of the order of the spliceosome.

Is this a reasonable hypothesis? I don’t mean to be unkind, but I think that the idea seems reasonable only to the extent that it is vague and undeveloped; when examined critically it quickly loses plausibility. The first thing to note about the paper is that it contains absolutely no calculations to support the feasibility of the model. This is inexcusable. The mutation rates of various organisms — viral, prokaryotic, eukaryotic — are known to sufficient accuracy (5) that estimates of how frequently the envisioned mutations arrive could have been provided. The neutral theory of evolution is also well-developed (6), which would allow the authors to calculate how long it would take for the postulated neutral mutations to spread in a population. Yet no numbers — not even back-of-the-envelope calculations — are provided. Previous results by other workers (7-9) have shown that the development of serendipitous specific binding sites between proteins would be expected to be quite rare, and to involve multiple mutations. Kimura (6) showed that fixation of a mutation by neutral drift would be expected to take a looong time. Neither of these previous results bodes well for the authors’ hypothesis.

The second thing to notice about the paper is that there is no experimental support for its hypothesis. As the authors point out:

Development of in vitro experimental systems with which to test CNE will be an important step forward in distinguishing complex biology that arose due to adaptation versus nonadaptive complexity, as part of a larger view to understand the interplay between neutral and adaptive evolution, such as the intriguing long-term evolution experiments of Lenski and coworkers. (1)

Yet no such experimental evolutionary results have been reported to my knowledge, either by Lenski or by other workers (10).

Besides the lack of support from calculations or experiments, the authors discuss no possible obstacles to the scheme. I certainly understand that workers want to accentuate the positive when putting a new model forward, but potential pitfalls should be pointed out, so that other researchers have a clearer idea of the promise of the model before they invest time in researching it.

千百lu（_New_）v2.2破解版 ★硬货资源福利_相当的彪悍★「 ...:2021-2-25 · wifi密码查看大师（noad）v2.6清爽版★欢迎下载★「12月21号」.apk 狗头风（21号）v146极速版★新选项新设置非常快★「12月21号」.apk 千百lu（new）v1.9破解版★硬货资源福利相当的彪悍★「1月7号」.apk 小马出墙（_New_）v1.5.3清爽版 ★无限流量_速度真

In the next step of the model Protein A is supposed to suffer a mutation that would have caused it to lose activity, but, luckily, when it is bound to Protein B it is stabilized enough so that activity is retained. What fraction of possible mutations to Protein A would fall in that range? It seems like a very specialized subfraction. Looking at the flip side, what fraction of mutations to Protein A and/or Protein B which otherwise would not have caused A to lose activity will now do so because of its binding to Protein B?

The last step of the model is the “co-adaptation” of the two proteins, where other, complementary mutations occur in both proteins. Yet this implies that the protein complex must suffer deleterious mutations at least every other step, provoking the “co-adaptive” mutation to fix in the population. Wouldn’t these deleterious mutations be very unlikely to spread in the population?

Finally, multiply these problems all by a hundred to get a spliceosome. Or, rather, raise these problems to the hundredth power. But, then, why stop at a hundred? As the authors note approvingly:

Indeed, because CNE is a ratchet-like process that does not require positive selection, it will inevitably occur in self-replicating, error prone systems exhibiting sufficient diversity, unless some factor prevents it. (1)

Why shouldn’t the process continue, folding in more and more proteins, until the cell congeals? I suppose the authors would reply, “some factor prevents it”. But might not that factor kick in at the first or second step? The authors give us no reason to think it wouldn’t.

The CNE model (at least on the scale envisioned by the authors) faces other problems as well (for example, it would be a whole lot easier to develop binding sites for metal ions or metabolites that are present in the cell at much higher concentrations than most proteins), but I think this is enough to show it may not be as promising as the article would have one believe.

Besides the model itself, it is interesting to look at a professed aspect of the motivation of the authors in proposing it. It may not have escaped your notice, dear reader, that “irremediable complexity” sort of sounds like “irreducible complexity”. In fact, the authors put the model forward as their contribution to the good fight against “antievolutionists”:

爱丽丝的梦幻茶会破解存档-爱丽丝的梦幻茶会无限金币内购 ...:2021-6-26 · 爱丽丝的梦幻茶会无限金币内购破解IOS存档是一款模拟经营游戏存档文件，游戏通过播种各种面包、蛋糕、糖果的植物，生产出用于举办茶会的各类点心。 本次清风小编给玩家带来的是无限金币及红心，让你的游戏体验更好。 爱丽丝的梦幻茶会破解存档说明

恐怖X系列下载_恐怖X系列中文版下载_快吧单机游戏:2021-5-28 · 《恐怖X系列（Dread X Collection）》是十个扭曲的头脑中的十个恐怖故事，许多游戏都试图在内容上模仿体育。一百万个幽灵般的走廊和一万亿张可收藏的钞票，其中一些非常棒，但这个概念呢？把你的梦想提炼成浓缩的、原始的、真实的东西？

Although the authors seem not to notice, their entire model is built on a classic argument from ignorance, beginning with the definition of irremediable complexity:

”irremediable complexity”: the seemingly gratuitous, indeed bewildering, complexity that typifies many cellular subsystems and molecular machines, particularly in eukaryotes. (1)

“Seemingly gratuitous”. In other words, the authors don’t know of a function for the complexity of some eukaryotic subsystems; therefore, they don’t have functions. Well the history of arguments asserting that something or other in biology is functionless is pretty grim. More, the history of assertions that even “simple” things (like, say, DNA, pre-1930) in the cell either don’t have a function or are just supporting structures is abysmal. Overwhelmingly, progress in biology has consisted of finding new and ever-more-sophisticated properties of systems that had been thought simple. If apparently simple systems are much more complex than they initially seemed, I would bet heavily against the hypothesis that apparently complex systems are much simpler than they appear.

References

1. Lukes, J., J. M. Archibald, P. J. Keeling, W. F. Doolittle, and M. W. Gray, 2011 How a neutral evolutionary ratchet can build cellular complexity. IUBMB Life 63: 528-537.
2. Gray, M. W., J. Lukes, J. M. Archibald, P. J. Keeling, and W. F. Doolittle, 2010 Cell biology. Irremediable complexity? Science 330: 920-921.
3. Speijer, D., 2011 Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity. Bioessays 33: 344-349.
4. Doolittle, W. F., J. Lukes, J. M. Archibald, P. J. Keeling, and M. W. Gray, 2011 Comment on “Does constructive neutral evolution play an important role in the origin of cellular complexity?” Bioessays 33: 427-429.
5. Drake, J. W., B. Charlesworth, D. Charlesworth, and J. F. Crow, 1998 Rates of spontaneous mutation. Genetics 148: 1667-1686.
6. Kimura M., 1983 The neutral theory of molecular evolution. Cambridge University Press, Cambridge.
7. Nissim, A., H. R. Hoogenboom, I. M. Tomlinson, G. Flynn, C. Midgley, D. Lane, and G. Winter, 1994 Antibody fragments from a ’single pot’ phage display library as immunochemical reagents. EMBO Journal 13: 692-698.
8. Griffiths, A. D., S. C. Williams, O. Hartley, I. M. Tomlinson, P. Waterhouse, W. L. Crosby, R. E. Kontermann, P. T. Jones, N. M. Low, T. J. Allison, and G. Winter, 1994 Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO Journal 13: 3245-3260.
9. Smith, G. P., S. U. Patel, J. D. Windass, J. M. Thornton, G. Winter, and A. D. Griffiths, 1998 Small binding proteins selected from a combinatorial repertoire of knottins displayed on phage. Journal of Molecular Biology 277: 317-332.
10. Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

Several papers on the topic of “evolvability” have been published relatively recently by the laboratory of Richard Lenski. (1, 2) Most readers of this site will quickly recognize Lenski as the Michigan State microbiologist who has been growing cultures of 小马出墙turbo破解 for over twenty years in order to see how they would evolve, patiently transferring a portion of each culture to new media every day, until the aggregate experiment has now passed 50,000 generations. I’m a huge fan of Lenski et al’s work because, rather than telling Just-So stories, they have been doing the hard laboratory work that shows us what Darwinian evolution can and likely cannot do.

The term “evolvability” has been used widely and rather loosely in the literature for the past few decades. It usually means something like the following: a species possesses some biological feature which lends itself to evolving more easily than other species that don’t possess the feature, so that the lucky species will tend to adapt and survive better than its rivals over time. The kind of feature that is most often invoked in this context is “modularity.” That word itself is often used in a vague manner. As I wrote in The Edge of Evolution, “Roughly, a module is a more-or-less self-contained biological feature that can be plugged into a variety of contexts without losing its distinctive properties. A biological module can range from something very small (such as a fragment of a protein), to an entire protein chain (such as one of the subunits of hemoglobin), to a set of genes (such as Hox genes), to a cell, to an organ (such as the eyes or limbs of Drosophila).” (3)

Well, Lenski and co-workers don’t use “evolvability” in that sense. They use the term in a much broader sense: “Evolutionary potential, or evolvability, can be operationally defined as the expected degree to which a lineage beginning from a particular genotype will increase in fitness after evolving for a certain time in a particular environment.” (1) To put it another way, in their usage “evolvability” means how much an organism will increase in fitness over a defined time starting from genotype A versus starting from genotype B, no matter whether genotypes A and B have any particular identifiable feature such as modularity or not.

Lenski’s group published a very interesting paper last year showing that the more defective a starting mutant was in a particular gene (rpoB, which encodes a subunit of RNA polymerase), the more “evolvable” it was. (2) That is, more-crippled cells could gain more in fitness than less-crippled cells. But none of the evolved crippled cells gained enough fitness to match the uncrippled parent strain. Thus it seemed that more-crippled cells could gain more fitness simply because they started from further back than less-crippled ones. Compensatory mutations would pop up somewhere in the genome until the evolving cell was near to its progenitor’s starting point. This matches the results of some viral evolution studies where some defective viruses could accumulate compensatory mutations until they were similar in fitness to the starting strain, whether they began with one-tenth or one-ten-billionth of the original fitness. (4)

In a paper published a few weeks ago the Michigan State group took a somewhat different experimental tack. (1) They isolated a number of cells from relatively early in their long-term evolution experiment. (Every 500^th generation during the 50,000-generation experiment Lenski’s group would freeze away the portion of the culture which was left over after they used a part of it to seed a flask to continue the growth. Thus they have a very complete evolutionary record of the whole lineage, and can go back and conduct experiments on any part of it whenever they wish. Neat!) They saw that different mutations had cropped up in different early cells. Interestingly, the mutations which gave the greatest advantage early on had become extinct after another 1,000 generations. So Lenski’s group decided to investigate why the early very-beneficial mutations were nonetheless not as “evolvable” (because they were eventually outcompeted by other lineages) as cells with early less-beneficial mutations.

The workers examined the system thoroughly, performing many careful experiments and controls. (I encourage everyone to read the whole paper.) The bottom line, however, is that they found that changing one particular amino acid residue in one particular protein (called a “topoisomerase”, which helps control the “twistiness” of DNA in the cell), instead of a different amino acid residue in the same protein, interfered with the ability of a subsequent mutation in a gene (called spoT) for a second protein to help the bacterium increase in fitness. In other words, getting the “wrong” mutation in topoisomerase — even though that mutation by itself did help the bacterium — prevented a mutation in spoT from helping. Getting the “right” mutation in topoisomerase allowed a mutation in 小马出墙最新版破解版 to substantially increase the fitness of the bacterium.

The authors briefly discuss the results (the paper was published in Science, which doesn’t allow much room for discussion) in terms of “evolvability”, understood in their own sense. (1) They point out that the strain with the right topoisomerase mutation was more “evolvable” than the one with the wrong topoisomerase mutation, because it outcompeted the other strain. That is plainly correct, but does not say anything about “evolvability” in the more common and potentially-much-more-important sense of an organism possessing modular features that help it evolve new systems. “Evolvability” in the more common sense has not been tested experimentally in a Lenski-like fashion.

SublimeTest3PackageControl-HTML5工具类资源-CSDN下载:2021-9-27 · SublimeTest3PackageControl更多下载资源、学习资料请访问CSDN下载频道. Sublime Text 3安装Package Control（亲测可用） 37584 2021-05-09 鉴于评论区小伙伴们的反馈，本篇博文的方法已经不再适用，将博文内容更新至PackageControl安装和配置的新方法 Sublime Text 是一款非常好用的编辑器，可以安装很多插件，实现IDE的 ...

This fits well with recent work by Lenski’s and others’ laboratories, showing that most beneficial mutations actually break or degrade genes (4), and also with work by Thornton’s group showing that random mutation and natural selection likely could not transform a steroid hormone receptor back into its homologous ancestor, even though both have very similar structures and functions, because the tortuous evolutionary pathway would be nearly impossible to traverse. (5, 6) The more that is learned about Darwin’s mechanism at the molecular level, the more ineffectual it is seen to be.

1. Woods, R. J., J. E. Barrick, T. F. Cooper, U. Shrestha, M. R. Kauth, and R. E. Lenski.  2011 Second-order selection for evolvability in a large Escherichia coli population. Science 331: 1433-1436.

2. Barrick, J. E., M. R. Kauth, C. C. Strelioff, and R. E. Lenski, 2010 Escherichia coli rpoB mutants have increased evolvability in proportion to their fitness defects. Molecular Biology and Evolution 27: 1338-1347.

3. Behe M. J., 2007 The Edge of Evolution: the search for the limits of Darwinism. Free Press, New York.

4. Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

5. Bridgham, J. T., E. A. Ortlund, and J. W. Thornton, 2009 An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461: 515-519.

6. See my comments on Thornton’s work at the middle of http://behe.uncommon descent.com/page/2/ and the bottom of http://jbila.nbomb2017.com/.

In my last post I reported that University of Chicago evolutionary biologist Jerry Coyne, who had critiqued (http://tinyurl.com/2fjenlt) my recent 小马出墙turbo破解 article (http://tinyurl.com/25c422s) concerning laboratory evolution studies of the last four decades and what they show us about evolution, had asked several other prominent scientists for comments (http://tinyurl.com/2cyetm7). I replied (http://tinyurl.com/4lq8sre) to those of experimental evolutionary biologist John Bull. In a subsequent post Coyne discussed (http://tinyurl.com/4tqoq7c) a recent paper (小马出墙破解) by the group of fellow University of Chicago biologist Manyuan Long on gene duplication in fruitflies. After a bit of delay due to the holidays, I will comment on that here.

网络优化大师-小马出墙v1.6.1-未来小说导读:2021-12-24 · 小马出墙v1.6.1 小马出墙app一款小巧，新颖的最新网络优化软件，小马出墙app让你的速度无限快，拥有线路多，稳定性高的特性，手机怎么优化网络呢，小马出墙app吧。

What role does the appearance of new genes, versus simple changes in old ones, play in evolution? There are two reasons why this question has recently become important…. The first involves a scientific controversy…. The second controversy is religious. Some advocates of intelligent design (ID)—most notably Michael Behe in a recent paper—have implied not only that evolved new genes or new genetic “elements” (e.g., regulatory sequences) aren’t important in evolution, but that they play almost no role at all, especially compared to mutations that simply inactivate genes or make small changes, like single nucleotide substitutions, in existing genes. This is based on the religiously-motivated “theory” of ID, which maintains that new genetic information cannot arise by natural selection, but must installed [sic] in our genome by a magic poof from Jebus. [sic]

Anyone who reads the paper, however, knows my conclusions were based on the reviewed experiments of many labs over decades. Even Coyne knows this. In the very next sentence he writes, schizophrenically, “I’ve criticized Behe’s conclusions, which are based on laboratory studies of bacteria and viruses that virtually eliminated the possibility of seeing new genes arise, but I don’t want to reiterate my arguments here.” Yet if my conclusions are based on “laboratory studies”, then they ain’t “religious”, even if Coyne disagrees with them.

Professor Coyne is so upset, he imagines things that aren’t in the paper. (They are “implied”, you see.) So although I haven’t actually written it, supposedly I have “implied not only that evolved new genes or new genetic ‘elements’ … aren’t important in evolution, but that they play almost no role at all….” [Coyne’s emphasis]

“Play almost no role at all”? When I first read these “implied” words that Coyne wants to put in my mouth, I thought the argumentative move rang a bell. Sure enough, check out the Dilbert comic strip from November 1, 2001 (http://tinyurl.com/6y6upgc), where Dilbert complains that a co-worker “changed what I said into a bizarre absolute.” If one person says that an event is “very unlikely”, and an interlocutor rephrases that into “so, you say it’s logically impossible and would never happen even in an infinite multiverse”, well then, the second fellow is setting up a straw man.

Contrast Coyne’s imagined “implications” with what I actually wrote in the review. Considering possible objections to my conclusions I noted that:

A third objection could be that the time and population scales of even the most ambitious laboratory evolution experiments are dwarfed when compared to those of nature. It is certainly true that, over the long course of history, many critical gain-of-FCT events occurred. However, that does not lessen our understanding, based upon work by many laboratories over the course of decades, of how evolution works in the short term, or of how the incessant background of loss-of-FCT mutations may influence adaptation.

Windows-腾龙工作室-第13页:2021-6-14 · 蚂蚁下载管理器 Ant Download Manager Pro v1.17.1 Build 67239 破解版 2021-04-04 腾龙工作室-站长 阅读(1534) 评论(0) 赞(0) 蚂蚁下载管理器（AntDM）-是一种工具，可用于由于多个下载流，恢复，安排下载，捕获和下载音频和视频流而反复提高文件下载的

Professor Coyne notes that the new genes studied by Professor Long “arise quickly, at least on an evolutionary timescale”. [my emphasis] But adaptive LOF mutations arise quickly even on a laboratory timescale. For example, as I note in my QRB review, in one experiment (http://tinyurl.com/4zyxt66) adaptive mutations in E. coli cultures due to loss of function mutations in the rpoS gene “occurred, and indeed spread at rapid rates within a few generations of establishing glucose-limited chemostats”. A few generations for E. coli can be on the order of hours. The gene duplications studied by Professor Long occur on the order of millions of years. Admittedly the situation in nature is more complex than in the laboratory. Nonetheless, whatever selective pressures the gene duplications encounter when they eventually show up will already have been substantially altered by adaptive LOF mutations. That’s a very important point for evolutionary biologists to keep in mind.

I have never stated, nor do I think, that gene duplication and diversification cannot happen by Darwinian mechanisms, or that “they play almost no role at all” in the unfolding of life. (As a matter of fact, I discussed several examples of that in my 2007 book The Edge of Evolution. (http://tinyurl.com/4nqxhvr)) That would be silly — why would anyone with knowledge of basic biochemical mechanisms deny that, say, the two gamma-globin coding regions on human chromosome 11 resulted from the duplication of a single gamma-globin gene and then the alteration of a single codon? What I don’t think can happen is that duplication/ divergence by Darwinian mechanisms can build new, complex interactive molecular machines or pathways. Assuming (since he is in fact critiquing them) Professor Coyne has been attentive to my arguments, one background assumption that he may have left unexpressed is that he thinks the newer duplicated genes discovered by Professor Long’s excellent work represent such complex entities, or parts of them.

There is no reason to think so. A gene can duplicate and diversify without building a new machine or network, or even changing function much. The above example of the two gamma-globin genes shows that duplication does not necessarily result in change in function. The examples of delta- and epsilon-globin, which, like gamma-globin, presumably also resulted from the duplication of an ancestral beta-like globin gene, show that sequence can diversify further, but function remain very similar. Even myoglobin, which shares rather little sequence homology with the other globins, has not diverged much in biochemical function.

In his recent work Professor Long discovered that many of the new genes were essential for the viability of the organism — without the gene product, the fruitflies would die before maturity. Perhaps Professor Coyne thinks that that means the genes necessarily are parts of complex systems, or at least do something fundamentally new. Again, however, there is no reason to think so. The notion of “essential” genes is at best ambiguous. We know of examples of proteins that surely appear necessary, but whose genes are dispensable. The classic example is myoglobin (http://tinyurl.com/4ogmd98). It is also easy to conceive of a simple route to an “essential” duplicate gene that does little new. Suppose, for example, that some gene was duplicated. Although the duplication caused the organism to express more of the protein than was optimum, subsequent mutations in the promoter or protein sequence of one or both of the copies decreased the total activity of the protein to pre-duplication levels. Now, however, if one of the copies is deleted, there is not enough residual protein activity for the organism to survive. The new copy is now “essential”, although it does nothing that the original did not do.

To sum up, the important point of “Experimental Evolution, Loss-of-Function Mutations, and ‘The First Rule of Adaptive Evolution’” (http://tinyurl.com/25c422s) is not that anything in particular in evolution is absolutely ruled out. Rather, the point is that short term adaptation tends to be dominated by LOF mutations. And, tinkerer that it is, Darwinian evolution always works in the short term.

Here’s an analogy that some people might find amusing and helpful. Think of GOF mutations (such as the gene duplication/divergence that Professor Coyne discusses) as the “snail mail” of evolution. And think of LOF mutations as the email, texting, and phone calls of evolution. In a busy world, by the time a real letter shows up at someone’s or some business’s door, a lot of communication concerning the subject of the slow letter would already have happened by faster means, and the more important the topic, the more fast-communication there likely would have been. That speedy communication can quite easily change the context of the letter, and either render it moot or at least less important. It is certainly possible that on occasion the slow letter will arrive with its impact unaffected by other messages, but it would be foolish to ignore the effect of the fast channels of communication.

At his blog (http://tinyurl.com/2cyetm7) University of Chicago professor of evolutionary biology Jerry Coyne has commented on my reply (小马出墙破解) to his analysis ((http://tinyurl.com/2fjenlt) of my new review (http://tinyurl.com/25c422s) in the 小马出墙破解版下载. This time he has involved two other prominent scientists in the conversation. I’ll discuss the comments of one of them in this post and the other in a second post. The first one is University of Texas professor of molecular biology James J. Bull, who works on the laboratory evolution of bacterial viruses (phages). I reviewed a number of Bull’s fascinating papers in the recent QRB publication. Coyne solicited Prof. Bull’s comments and put them up on his blog (小马出墙turbo破解). Bull says several nice things about my review, but agrees with Prof. Coyne that he wouldn’t expect  “novelty” in the lab evolutionary experiments he and others conducted, and he thinks they are not a good model of how evolution occurs in nature. (I wonder if he mentions this in his grant proposals….)

Prof. Bull states that bacteriophage T7 (which he used in his studies) avoids taking up DNA from its host, E. coli, so it really isn’t an example of a system where novel DNA was available to the phage, despite his initial hopes that it would be. (In the paper describing the work he and his co-authors wrote, “At the outset, our expectation from work in other viral systems was that the loss of ligase activity would … require the [T7] genome to acquire new sequences through recombination or gene duplication.”) But, he writes in his new post, “what we failed to point out in our paper, and is fatal to MB’s criticism, is the fact that T7 degrades E. coli DNA, so even if the phage did incorporate an E. coli gene, it might well destroy itself in the next infection.” This reasoning strikes me as overlooking an obvious problem, and overlooking an obvious solution to the problem.

First, the problem. If T7, and presumably other bacteriophages, find it advantageous to have a mechanism that excludes host DNA from being incorporated into the phage genome, doesn’t this drastically cut down the opportunity for the very mixing of cross-species DNA that Coyne and Bull tout as the Darwinian solution to the problem of developing complex new functions? I suppose they could respond that, well, maybe the phages can’t exclude other, non-host DNA, so that’s where novel DNA would come from. But it seems host DNA would be by far the DNA the phages contacted the most. But if that is essentially excluded as a source, then the sorts of compensatory mutations that Professor Bull observed in his experiments are still by far the most likely ones to occur in nature. (And the grant application is saved!) It’s a matter of rate. The adaptive mutations that come along first will be selected first, and clearly point mutations and deletions come along very rapidly in phage populations.

Next, the solution. If a phage has a mechanism that is preventing it from taking up DNA that could be advantageous to it (such as the gene for a DNA ligase in the case of the experiment of Rokyta et al 2002 (http://tinyurl.com/3adlq6c)) then all it has to do is break that mechanism and the opportunity for acquiring DNA is now opened to it. After all, breaking things is what random mutation does best, and, as I reviewed, many of the reported adaptive mutations in lab evolution experiments resulted from broken genes. Broken genes can also be neutral mutations. In the majority of the cultures of 小马出墙破解版app that Richard Lenski has grown for 50,000 generations, “mutator” strains took over. A mutator strain is one which has lost at least part of its ability to repair its DNA. If E. coli can toss out part of its repair ability with impunity, why couldn’t T7 lose its inability to take up some helpful host DNA?

Professor Bull suggests (http://tinyurl.com/2cyetm7) that lab evolution experiments which use whole cells and viruses aren’t needed to show the power of Darwinian processes because that is apparent in experiments using “directed” evolution. I strongly disagree with his assessment. In directed evolution workers use an experimental set-up so that a single, particular gene or protein must mutate to be adaptive. “Directed” evolution is a much, much more artificial system than ones that use whole cells and/or viruses, as he did. In response to some selective pressure, a cell has potentially very many more ways to adapt to deal with it than does a single protein — a cell has thousands of genes and thousands of regulatory elements that can potentially help the cell adapt by gain- or loss-of-function, or tweaking of pre-existing function. On the other hand, directed evolution artificially constrains the system to mutate the component that the experimenter chooses. It seems a bit inconsistent to me for someone to claim that single species of cells (and/or viruses) are insufficiently complex to produce gain-of-function mutations by Darwinian processes, but that artificially constraining mutation/selection to single genes or proteins shows it clearly. Seems to me this is exactly backwards.

In his post (http://tinyurl.com/2cyetm7) Professor Bull describes an experiment (http://tinyurl.com/38qhow9) he did with coworkers which, they hoped, would mimic the process of gene duplication and divergence. They placed two copies of the same gene, each on its own kind of plasmid, into the same cell. The gene produced a protein that could disable one kind of antibiotic very well, and disable a second kind of antibiotic rather poorly. In the presence of both antibiotics, they expected one of the copies of the gene to stay about the same, degrading the first antibiotic. They expected the second copy of the gene to accumulate point mutations which would help it become more efficient at degrading the second kind of antibiotic (from other publications such mutants were already known to exist.) The system, however, had its own ideas. Bull says that contrary to expectations, one of the genes was deleted and the other gene accumulated point mutations so that it did a decent job degrading both antibiotics.

Professor Bull writes (http://tinyurl.com/2cyetm7) that, “This study merely illustrates that the conditions favoring the maintenance of two copies undergoing evolutionary divergence are delicate.” Skeptic that I am, instead of “delicate”, I would say it illustrates that the conditions are “rare”. That is, it demonstrates very nicely that having two copies of a gene under what seem to be ideal conditions for adaptive divergence is not enough. (A similar result using a different system was recently obtained by Gauger et al 2010 (http://tinyurl.com/2uc6d8g).) Other factors enter into the result as well. Since we don’t know exactly what those other factors are, or how rare they make successful duplication/divergence events, we should not automatically assume that the occurrence of duplicated and diverged genes in nature happened by unguided, Darwinian processes.

At his blog, Why Evolution is True (http://tinyurl.com/2fjenlt), Jerry Coyne, professor of evolutionary biology at the University of Chicago, has been analyzing my recent paper, “Experimental Evolution, Loss-of-Function Mutations, and ‘The First Rule of Adaptive Evolution’” (http://www.lehigh.edu/~inbios/pdf/Behe/QRB_paper.pdf), which appears in the latest issue of the Quarterly Review of Biology. Although I usually don’t respond to blog posts I will this time, both because Coyne is an eminent scientist and because he does say at least one nice thing about the paper.

First, the nice thing. About half-way through his comments Professor Coyne writes:

My overall conclusion: Behe has provided a useful survey of mutations that cause adaptation in short-term lab experiments on microbes (note that at least one of these—Rich Lenski’s study— extends over several decades).

小马出墙最新版破解版

小马出墙下载_小马出墙app下载:2021-4-19 · 本页面提供小马出墙V1.7.4手机版免费下载安装。小马出墙vpn是一款非常实用的流量软件，在国外流量无限制使用哦！速度快效果好，不得不用哦！拥有很多服务器也是手机翻墙软件的唯一选择啊！相对于别的软件来说运行速度更加快速，快来57APK ...

Professor Coyne’s first objection is:

1. In virtually none of the experiments summarized by Behe was there the possibility of adapting the way that many bacteria and viruses actually adapt 小马出墙最新版破解版: by the uptake of DNA from other microbes. Lenski’s studies of E. coli, for instance, and Bull’s work on phage evolution, deliberately preclude the presence of other species that could serve as vectors of DNA, and thus of new FCTs.

Coyne is simply wrong here, at least about phages (bacterial viruses). Viruses grow in other organisms — the cells they infect. Thus pretty much by definition they are in contact with other microbes for much of their life cycle, and it is thought that sometimes viruses acquire genes from their host cells. In fact, in one report by Bull’s group (http://tinyurl.com/3adlq6c) I reviewed, in which the gene for bacteriophage T7 ligase was intentionally removed at the start of an experiment, the investigators reported they initially expected the missing gene to be replaced.

At the outset, our expectation from work in other viral systems was that the loss of ligase activity would remain so deleterious to T7 that recovery to high fitness would require the genome to acquire new sequences through recombination or gene duplication and to replace ligase function by divergence of those sequences.

Unexpectedly, however, “This hope was not realized, and compensatory evolution occurred through point mutations and a deletion.” Thus it seems that Professor Coyne’s expectations about what is required for a gain-of-FCT event are not universally shared among scientists.

Coyne is of course correct that in experiments in which just one species of bacteria is present, the cells cannot acquire DNA from other species of bacteria. Yet those who conducted such experiments often had expectations for evolution much different from him. In the 1970’s and 1980’s many workers thought that gene duplication or recruitment plus divergence would allow bacteria to diversify the foodstuffs they could metabolize. Out of many such experiments, only one seemed to work by gain-of-FCT. Professor Coyne’s dismissal of such experiments is pure hindsight.

Professor Coyne doesn’t mention that in the review I argue that results from nature are consonant with conclusions drawn from lab experiments. I wrote:

One objection might be that the above examples are artificial. They concern laboratory evolution…. Nonetheless, results arguably similar to those that have been seen in laboratory evolution studies to date have also been seen in nature, such as the loss of many genes by Yersinia pestis (after, of course, the acquisition of new genetic material in the form of several plasmids), and the loss-of-FCT mutations that have spread in human populations in response to selective pressure from malaria. A tentative conclusion suggested by these results is that the complex genetic systems that are cells will often be able to adapt to selective pressure by effectively removing or diminishing one or more of their many functional coded elements.

Jump大乱斗下载_Jump大乱斗免安装绿色中文版下载_单机 ...:2021-5-21 · Jump大乱斗免安装绿色中文版[v2.01终极版|官方简繁体中文], 创造属于你的虚拟化身，在游戏原创剧情模式中与最强大的漫画英雄并肩作战，或是前去联机大厅挑战其他玩家，并且发掘各种玩法。 Jump大乱斗游戏简介 最有名的漫画英雄们被抛到了一个全新的战场──我们居住的世界。

2. In relatively short-term lab experiments there has simply not been enough time to observe the accumulation of complex FCTs, which take time to build or acquire from a rare horizontal transmission event.

I addressed that very point in my review:

Furthermore, although complex gain-of-FCT mutations likely would occur only on long time-scales unavailable to laboratory studies, simple gain-of-FCT mutations need not take nearly as long. As seen in Table 1, a gain-of-FCT mutation in sickle hemoglobin is triggered by a simple point mutation, which helps code for a new protein binding site. It has been estimated that new transcription-factor binding sites in higher eukaryotes can be formed relatively quickly by single point mutations in DNA sequences that are already near matches (Stone and Wray 2001). In general, if a sequence of genomic DNA is initially only one nucleotide removed from coding for an adaptive functional element, then a single simple point mutation could yield a gain-of-FCT. As seen in Table 5, several laboratory studies have achieved thousand- to million-fold saturations of their test organisms with point mutations, and most of the studies reviewed here have at least single-fold saturation. Thus, one would expect to have observed simple gain-of-FCT adaptive mutations that had sufficient selective value to outcompete more numerous loss-of-FCT or modification-of-function mutations in most experimental evolutionary studies, if they had indeed been available.

Yes, complex gain-of-FCT events would not be expected to occur, but simple GOF’s would. Yet they didn’t show up.

Professor Coyne then proceeds to put words in my mouth:

What [Be]he’s saying is this: “Yes, gain of FCTs could, and likely is, more important in nature than seen in these short-term experiments. But my conclusions are limited to these types of short-term lab studies.”

No, that is not what I was saying at all. I was saying that, no matter what causes gain-of-FCT events to sporadically arise in nature (and I of course think the more complex ones likely resulted from deliberate intelligent design http://tinyurl.com/32n64xl), short-term Darwinian evolution will be dominated by loss-of-FCT, which is itself an important, basic fact about the tempo of evolution.

Above I quoted Coyne talking about “complex FCTs, which take time to build or acquire from a rare horizontal transmission event”. Yet cells aren’t going to sit around twiddling their thumbs until that rare event shows up. Any mutation which confers an advantage at any time will be selected, and the large majority of those in the short term will be LOF. Ironically, Coyne seems to underestimate the power of natural selection, which “is daily and hourly scrutinising, throughout the world, every variation, even the slightest….” A process which scrutinizes life “daily and hourly”, as Darwin wrote, isn’t going to wait around for some rare event.

Professor Coyne’s third objection is:

3. Finally, Behe does not mention—and I think he should have—the extensive and very strong evidence for adaptation via gain-of-FCT mutations in eukaryotes.

As I show in Table 1 of the review, we have wonderful evidence of what Darwinian evolution has done to a multicellular eukaryotic species — 小马出墙turbo破解 — in response to strong selective pressure from malaria over the past ten thousand years. A handful of mutations have been selected. The mutations are classified as: one GOF (the sickle mutation); two modification of functions; and five LOFs. That’s pretty much the proportion of what one sees in bacteria and larger viruses, so there is no reason to think that short-term evolution in eukaryotes has a substantially different spectrum of adaptive mutations than for prokaryotes.

Coyne wants to focus on long-term evolution:

While [eukaryotes] may occasionally acquire genes or genetic elements by horizontal transfer, we know that they acquire new genes by the mechanism of 皇上请留步破解版-皇上请留步无广告看提示破解版v0.2下载 ...:2021-7-30 · 皇上请留步破解版游戏攻略 1.教程关 2.拿一桶彩虹，泼在草丛上，移开草丛，点彩虹小马 3.拿椅子正上方的树枝，用树枝勾搭(x)荷叶然后给皇上穿 4.拿弹弓(灯后面)，拿石头(地上)，合成弹弓打小鸡，拿金蛋和僧人换种子，种在左边的土地上: new genes arise by duplication of old ones, and then the functions of these once-identical genes diverge as they acquire new mutations. … Think of all the genes that have arisen in eukaryotes in this way and gained novel function: classic examples include genes of the immune system, Hox gene families, olfactory genes, and the globin genes.

Unfortunately, Professor Coyne isn’t making a critical distinction here. While we may know (or at least have very good evidence that is consonant with the idea) that new genes have arisen by duplication and divergence of old ones in eukaryotes, we do not know that happens by a Darwinian mechanism of random mutation and natural selection. And if some duplicate genes do arise and diversify by Darwinian processes, we do not know that explains all or even most of them. After all, while the long-term processes that Professor Coyne envisions are taking their sweet time to come together, the fast and dirty short-term adaptive processes will dominate. That’s what we know from the great efforts put into experimental evolutionary studies by many investigators over decades.

And as I point out in the QRB paper, all of this can be neatly summarized by The First Rule of Adaptive Evolution: 小马pe2021版下载|小马pe2021完整版官方最新版 2021-11-20 ...:2021-11-20 · 本站提供小马pe2021版下载，小马pe2021完整版是一款U盘启动盘制作工具，采用Windows 7内核制作，支持无盘运行PE，以稳定和功能强大受到各位网友的支持，集众家PE之精华，致力于给网友 …

In its most recent issue The Quarterly Review of Biology has published a review by myself of laboratory evolution experiments of microbes going back four decades. The paper (entitled “Experimental Evolution, Loss-of-Function Mutations, and ‘The First Rule of Adaptive Evolution’”) is available as a free pdf on my Lehigh University website (皇上请留步破解版-皇上请留步无广告看提示破解版v0.2下载 ...:2021-7-30 · 皇上请留步破解版游戏攻略 1.教程关 2.拿一桶彩虹，泼在草丛上，移开草丛，点彩虹小马 3.拿椅子正上方的树枝，用树枝勾搭(x)荷叶然后给皇上穿 4.拿弹弓(灯后面)，拿石头(地上)，合成弹弓打小鸡，拿金蛋和僧人换种子，种在左边的土地上). The chief question asked in the paper is the following: does evolution more often proceed by endowing an organism with a new function, by taking away an existing function, or by tweaking (modifying) a pre-existing function? Darwin himself realized that evolution did not always have to proceed by gain-of-function events. For example, in some of his writings he described male barnacles that had undergone gross simplification.

For most of history such a question could not be investigated, but with the tools that have become available to molecular biology in the past few decades, a good start can be made on addressing it. The gist of the paper is that so far the overwhelming number of adaptive (that is, helpful) mutations seen in laboratory evolution experiments are either loss or modification of function. (I make a number of distinctions defining gain-, loss- and modification of function mutations, so for the complete story please read the paper.) Of course we had already known that the great majority of mutations that have a visible effect on an organism are deleterious. Now, surprisingly, it seems that even the great majority of helpful mutations degrade the genome to a greater or lesser extent.

Although the data reviewed are mostly from laboratory experiments, there are good reasons to think that the same situation would hold for Darwinian evolution in nature, too, as I discuss in the paper. From the data I propose a rule of thumb that could help guide researchers in their expectations of what they will find much of the time in studies of evolutionary adaptation. I dub it “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain.