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Monday, November 26, 2018

Deflated egos and the G-value paradox

The Deflated Ego Problem refers to the fact that many scientists were very disappointed to learn we had less than 30,000 genes. Those scientists were expecting that the human genome would contain many more genes in line with their belief that humans must be genetically more complex than the "lower" animals. They should have known better since knowledgeable experts were predicting fewer than 30,000 genes and these same experts knew that humans don't need many more genes than other animals [see: Revisiting the deflated ego problem].

Disappointed scientists don't use the term "deflated ego;" instead they refer to their problem as the G-value paradox. This makes it seem like a real problem instead of just a mistaken view of evolution.

I just read the original paper on the G-value paradox and I think it's worth quoting some of it because it clearly states the issues. The paper is by Matthew Hahn and Gregory Wray when they were both at Duke University in Durham, North Carolina, USA. (Hahn was a graduate student in Wray's lab, he is now a professor at Indiana University.) (Hahn and Wray, 2002). It's important to note that these are respected scientists and their views are still very popular.

They begin their brief review by expressing surprise that the human genome had "a surprisingly modest 31,000 genes." Then they explain why this is a problem.
Even though sequencing the human genome may be merely a first pass at a deeper understanding of our biology, one fact stands out as demanding an immediate explanation: Why do humans have so few genes?

The assumptions and chauvinism implicit in this question—that humans are vastly more complex than the other fully sequenced eukaryotes and should therefore have a commensurately larger suite of genes—are difficult to argue clearly and may be even more difficult to justify biologically. Still, it is hard to deny our intuitive perception that the number of genes in a genome should be roughly correlated with complexity and that organismal complexity can be ranked as yeast < nematodes < flies < humans (we reserve judgment on the relative position of the “green fly,” Arabidopsis). However, the number of genes in the genomes of these organisms does not match our naive expectation.
The is a perfect description of the Deflated Ego Problem—the number of genes did not match their naive expectation. Normally when a scientific result doesn't match your expectations—and you recognize that your expectations were "naive"—that would cause you to reevaluate your expectations, especially when you learn that other scientists did not share them.

That's not what happened in most cases. What usually happened is that disappointed scientists attempted to justify their naive expectations and then propose solutions that still make humans more genetically complex even though they have the same number of genes as other animals.

Here's what the justification looks like.
This disjunction between the number of genes and organismal complexity, what we call the “G‐value paradox,” parallels the finding during the 1950s that the physical size of genomes does not correlate with organismal complexity, a relationship known as the C‐value paradox. The finding that much of the genome contains noncoding repeats and “junk” DNA seemed to resolve the C‐value paradox. Implicitly, this resolution rested on the assumption that once noncoding DNA was taken into account, the total number of genes would then correlate with organismal complexity (Cavalier‐Smith 1985). However, the published G values of the completely sequenced eukaryotes make it clear that we have not yet resolved the C‐value paradox—it has merely given way to the G‐value paradox.
Do you see what they just did? They tried to convince you that other scientists were also expecting there to be more genes because humans are more complex. This "problem" even has a name: it's called the G-value paradox.

What they did not do in their paper was to mention that many knowledgeable scientists were predicting fewer genes and their predictions were backed up by solid evidence (e.g. Ewing and Green, 2000; Roest Collius et al., 2000). Nor did did they mention the idea coming from evo-devo that complexity doesn't correlate with the number of genes but with differential control of a core set of genes. I'm struggling to understand why there's so much resistance to this key concept that's strongly supported by data from a number of model organisms.

Here's what the "solution" to the G-value paradox looks like.
Just as the discovery of noncoding DNA seemed to resolve the C‐value paradox, so a few simple observations may in time resolve the G‐value paradox. These observations all attempt to give more value to each of our genes and thus to give us a more accurate genomic predictor of organismal complexity by identifying the true measure of information encoded by a genome, the "I‐value." Some of the observations we discuss here have been offered as the answer to explaining our modest number of genes, whereas some have been invoked in combination. These observations indicate that the evolution of organismal complexity will typically involve changes in the genome that are subtler than simply adding genes. The C‐value paradox was resolved by a plea to the G value; a resolution of the G‐value paradox may be offered by a plea to the I value.
The most common ways of giving "more value" to existing genes, according to Han and Wray, are alternative splicing, and posttranslational modifications. Both of these possibilities give you more bang for the buck with the same number of genes because each gene can produce multiple products.

We now know that neither process causes a significant increase in the number of gene products but, even in 2018, it's still widely believed that this is the answer to the G-value paradox.

As I mentioned above, I'm having difficulty understanding why the G-value paradox was created in the first place but that difficulty pales in comparison to my difficulty in understanding why it remains so popular in 2018. Perhaps my readers can help me out. Do you have a problem accepting that humans have about the same number of genes as other mammals, fish, or insects? If so, can you explain to me why you think this is a problem that demands a solution?


Ewing, B., and Green, P. (2000) Analysis of expressed sequence tags indicates 35,000 human genes. Nat Genet, 25:232-234. [doi:10.1038/76115]

Hahn, M.W., and Wray, G.A. (2002) The g-value paradox. Evolution and Development, 4:73-75. [doi: 10.1046/j.1525-142X.2002.01069.x]

Roest Crollius, H., Jaillon, O., Bernot, A., Dasilva, C., Bouneau, L., Fischer, C., Fizames, C., Wincker, P., Brottier, P., Quetier, F., Saurin, W., and Weissenbach, J. (2000) Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence. Nat Genet, 25:235-238. [doi:10.1038/76118]



52 comments :

  1. When I was a lowly undergraduate in the late 1970s, we discussed this issue in my genetics class…and the professor was quite clear that we might have a few more genes than Drosophila, but not by much, and there was no good reason to expect humans to have significantly more genes than other animals.

    I wonder where the people who are surprised by reality went to school.

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    1. Did this professor explain how DNA replication errors built functional genes? What school did he go to?

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  2. Note that Han & Wray also confuse "noncoding" with "junk", using the former term when they mean the latter.

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  3. Modern creationism would welcome people having the same number as critters because it makes sense from a common design stance. God would do it that way. not give different numbes just to make a point. All in biology works well with the same number. its a good idea.
    it shows biology is just twisted/tweeked into its diversity but is still from a (simple?) blueprint.
    In fact having different number of genes etc would be more welcome in a idea of evolutionism being random and selecting .and drifting, and generally as if from chance.
    As research/people do better things look better for a thinking being behind nature. I'm sure more to come.

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    1. A convincing argument. I'm sure the one explaining the wildly varying amounts of junk DNA in different species is just as convincing.

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    2. "Modern creationism would welcome people having the same number as critters because it makes sense from a common design stance. God would do it that way. "

      Okay, so since he clearly didn't, God can't have been responsible. Right?

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    3. Whenever evolutionary biologists discover some interesting new feature the response of creationists is always the same. The know the mind of god(s) so they are not surprised. After all, that's clearly the way god(s) would do it.

      You can be certain they would give the same response if it turned out that each species has a different set of genes. Apparently their god(s) can be very flexible.

      On the other hand, when it comes to things like the existence of evil, the standard response is that god(s) work in mysterious ways and we can't possibly understand his/her/its purpose.

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    4. You can see that inconsistency when they are confronted with bad-design arguments. No, they say, once cannot say that god(s) would not do it that way, one cannot presume to know what they intend. Which is fine, but in the case of junk DNA they make an argument totally inconsistent with that. It cannot be there, they say. Pressed as to why, it's because the Designer they have in mind would not do it that way.

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    5. A creationist can only answer it makes sense biology follows laws/order like in physics. So why not a better idea to have a common blueprint for biology and then it fits fine with a common number of genes etc for everyone?
      I think Einstein once said he asked himself WHAT would God do when trying to figure out physics stuff.
      creationists don't discover the equal numbers of genes but we can say AHA that makes sense as opposed to other options.
      I think evolutionism would easily welcome a diversity in gene numbers etc. tHey would say it fits with a mechanism thats founded on chance, or almost.

      Bad -design claims are just wrong ideas about biology.
      There was no bad design but then there was after problems came.
      Every bad-design can be explained especially from a YEC stance.
      This is, by the way, a strange way to preserve evolutionism. Your debunking the opposite option only here.
      Is it true that already thoughtful evolutionists realize they can't make a biological scientific case to justify evolution as a theory or hypothesis??

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  4. 31,000 genes permit 31,000! simple gene interactions, not to mention higher order interactions and the variable non-coding substrate on which these interactions may be modulated. There is enough complexity in flies, snails, or men to occupy molecular biologists at least several centuries.

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  5. Do these guys define the 'complexity' they want to explain, of do they just take an 'I know it when I see it' stance? Having an explicit definition might make the weaknesses of their arguments clearer.

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    1. I'm not so sure. Which makes the weakness of their arguments clearer -- having one or not having one?

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    2. The most common definition they use is the number of different types of cells and tissues. Using this definition they claim that humans are among the most complex organisms. They even seem to be more complex than other mammals but I’m not sure how that works.

      The nice thing about their definition of complexity is that humans are more complex than trees so it highlights the problem because we don’t have a lot more genes than trees. The inconvenient truth in their analysis is that plants have just as many transcript variants per gene as humans. I guess they’re all junk in plants but in humans they are examples of alternative splicing that increases diversity and complexity.

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    3. I think I read that Norwegian pine trees have >20 gigabasepair genome, and it's mostly retrotransposons.

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    4. How unambiguous are the criteria for 'different types of cells' across different kinds of organisms? Is our understanding of tree cell biology sufficient for us to be sure we're applying the same standards?

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    5. I haven’t looked closely at the references but my impression is that the data on cell types is okay but not great. It seems to be tilted in favour of humans ‘cause we know a lot more about how many distinct cells are present in human organs than in, say, bird organs or fish.

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    6. "it highlights the problem because we don’t have a lot more genes than trees"

      Yes, that does highlight an interesting problem. How DNA replication errors have resulted in the phenomenal versatility that human genes exhibit is difficult to imagine.

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    7. It's good we don't have to imagine it then, we can just look at the evidence and see that it has come mostly from three processes: 1) Gene dupication and divergence, 2) from de novo emergence of promoters in non coding DNA, and 3) from genetic recombination and exon shuffling.

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    8. "we can just look at the evidence and see that it has come mostly from three processes"

      How is the fact that they are there evidence for how they got there?

      If humans utilize 100,000 proteins, but only have 21,000 genes, which one of the three accidental processes you mention do you see as the big player in producing genes that code for multiple proteins?

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    9. "If humans utilize 100,000 proteins, but only have 21,000 genes"

      If.

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    10. "If."

      Do you dispute the numbers? There are other estimates:

      "As with genome size, having more protein-coding genes does not necessarily translate into greater complexity. This is because the eukaryotic genome has evolved other ways to generate biological complexity....In fact, scientists have estimated that there may be as many as 500,000 or more different human proteins, all coded by a mere 20,000 protein-coding genes."

      https://www.nature.com/scitable/topicpage/eukaryotic-genome-complexity-437

      The real problem though, is not about the numbers. It is about how in hell natural selection and random mutations "evolved other ways to generate biological complexity".

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    11. "Do you dispute the numbers?"

      Clearly, you haven't been reading much that Larry has posted, including the very post at the top of this page. Why not?

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    12. "...you haven't been reading"

      Oh, I read the post, and the questions posed at the end.

      ”Do you have a problem accepting that humans have about the same number of genes as other mammals, fish, or insects? If so, can you explain to me why you think this is a problem that demands a solution?”

      The answer is obvious, but it isn’t about the number of genes. It is about functional complexity. Complex systems make the mutations/selection idea look stupid, and hyper-complex systems make it look deluxe stupid. Genes coding for multiple proteins is an extremely sophisticated design. The Nature article I linked to touches on the concept:

      ”Consider again those 60,000 protein-coding genes in Trichomonas vaginalis. If all of those 60,000 genes operated at the same level of complexity as the 20,000 or so genes in Homo sapiens, then shouldn't T. vaginalis be a much more complex organism than it is? As it turns out, its genes do not operate at that same level of complexity.”

      The problem doesn’t really demand a solution, but it does call for a reasonable conclusion. Believing that random accidents result in fantastic innovation is not reasonable.

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    13. "Oh, I read the post, and the questions posed at the end."

      You probably should have read this one too.

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    14. The problem doesn’t really demand a solution, but it does call for a reasonable conclusion. Believing that random accidents result in fantastic innovation is not reasonable.

      Have you ever heard of "trial and error learning"?

      You need to study the concept. Humans work the same way. Your argument shows your ignorance.

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    15. "Have you ever heard of "trial and error learning”?… You need to study the concept”

      I’m sorry, but that concept doesn’t apply at all. It's all accidents. Nobody is trying, nobody is recognizing errors, and nobody is learning. You’ve just heard words like “tinkering” used for anthropomorphic effect. It is deceitful, but it has the intended effect. You’re not the first person who has been led to believe that evolution is smarter than you.

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    16. I’m sorry, but that concept doesn’t apply at all.

      I computer model this concept! You're up against a serious model/theory that is already being useful to experimenters in a number of "intelligence" related fields including robotics.

      Numenta is a popular neuroscientific research organization with an online community that is best able to understand and fairly judge the usefulness of computational biological models pertaining to how "intelligence" works, as I explained happening in genetic systems, cells and our brain. In all of "science" the Numenta online community is the best place in the world for the model/theory and I to be right now, which is why I discuss details there instead of elsewhere.

      https://discourse.numenta.org/t/will-we-ever-see-agi/5123/10

      https://discourse.numenta.org/t/intelligence-and-transfer-learning/3894/7

      https://discourse.numenta.org/t/intelligence-and-transfer-learning/3894/4

      https://discourse.numenta.org/t/oscillatory-thousand-brains-minds-eye-for-htm/3726

      It's all accidents. Nobody is trying, nobody is recognizing errors, and nobody is learning. You’ve just heard words like “tinkering” used for anthropomorphic effect. It is deceitful, but it has the intended effect. You’re not the first person who has been led to believe that evolution is smarter than you.

      A sentence like "It's all accidents." is tinkering with terminology that should have read "random mutation" to as Judge Jones found denigrate well tested scientific theory.

      This is how "intelligent cause" really works, giant mystery explained:

      https://theoryofid.blogspot.com/

      https://www.reddit.com/r/IDTheory/

      Much more information that you badly need:

      https://www.reddit.com/user/GaryGaulin

      What I have to say came from many thousands of hours spent conducting experiments with applicable computational models. My experience now helps write ahead of their time dissertations and such using most precise terminology for concepts relating to multiple-level intelligent systems and a model based definition that also works for IBM Watson, HTM Theory and rest of neuroscience.

      Throwing stones at what I explained caused your response to become destined to be a faded memory of a bully. This is a situation where you are forced to adapt to the existing scientific terminology and definitions, like I always have had to. So please try again.

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    17. ”A sentence like "It's all accidents." is tinkering with terminology….”

      No, it is just being candid. Random events cannot result in complexity and sophistication.
      -
      ”…as Judge Jones found denigrate well tested scientific theory.”

      No, it has not been tested at all. The scientific theory says that eyes (and every other biological thing) are the result of recurring, fortuitous DNA replication errors. It also says that everything that eyes (and every other biological thing) require, were produced by recurring, fortuitous DNA replication errors.

      This is, of course, an idiotic thing to believe, and the invocation of natural selection does not make it less idiotic. It is just looking for a deity.

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    18. “Are you familiar with the Dunning–Kruger effect?"

      Yes, I am. The illusion of cognitive superiority enables people to accept ideas that are either not supported by evidence, or refuted by profuse evidence. The fact that the disease databases cannot rattle the absurd beliefs associated with mutations are a good example. Combine the DKE with academic, political and cultural groupthink, and you have an iron-clad religion.

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    19. "How is the fact that they are there evidence for how they got there?"

      It isn't. It is the patterns in their sequences and distribution in different species, that is the evidence. Not the mere fact of their existence.

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    20. "For txpiper"

      Good grief. Okay, so let’s just assume that I’m addicted to religion, morphine, muffaletta sandwiches and Japanese girls. That doesn’t make your mutations problem go away. Have you even figured out that you have a problem yet? Do you comprehend why the supposed operational mechanism of evolution is a ridiculous idea?

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    21. txpiper, this blog format is not very conducive to this kind of discussion. You can register as a user on https://discourse.peacefulscience.org/ or on http://theskepticalzone.com/wp/ alternatively.

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    22. “No, why is it a problem?”

      Because nobody can explain how it works.

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    23. Then go ahead txpiper, tell us "how it works" so that we become as wise and knowing as you are.

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    24. “tell us "how it works" so that we become as wise and knowing as you are”

      I can’t, and you’ve missed the point. Let’s try this.

      From your point of view, once upon a time, mammals had not evolved from reptiles. But the mammary function (among other things) arose. Your theory says that this system is the result of powerful natural selection acting on multiple series of random, but complimentary mutations. Lots of novel subsystems and features are involved, in parent and offspring, things too numerous to list. So are the complications and obstacles.

      So what makes you believe that this, or anything like this, occurred….millions of times? You tell me how it works.

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    25. "I can’t,

      Why not?

      "and you’ve missed the point. Let’s try this."

      If you cannot explain anything at all about how the process (of evolution that fossil evidence beyond reasonable doubt proves happened) works then it's your theory that failed.

      ...... Your theory says that this system is the result of powerful natural selection acting on multiple series of random, but complimentary mutations.

      This is my theory:

      http://theoryofid.blogspot.com/

      How could you not know this after my earlier linking you to several places including what it looks like in computational neuroscience? Did you later forget what you read? Or did you not bother to study any of it?

      You tell me how it works.

      I develop cognitive models/theory of things that are intelligent. And for some reason you have no interest at all in evolution by natural selection theory that another way explains how the process of evolution works.

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  6. If you mean all possible pairwise combinations of 31,000 genes, that’s 31,000C2, which is (31,000!)/(2!((31,000-2)!)), which is only 480,484,500. If I remember my math, anyway.

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    1. Or much more simply 31,000 multiplied by 30,999 divided by 2.

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    2. The smart biology man up the thread says 2^n so he seems to be saying you have to add up nC0, nC1, nC2 ... nCn.

      I'm not qualified to opine but I did do a project on Pascal's triangle in grade 11 math. Made a very pretty poster. All the rows add to 2^n! where here I'm using ! as the punctuation and not the math thing.

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  7. Did you read the paper "Testing the retroelement invasion hypothesis for the emergence of the ancestral eukaryotic cell" (Lee et al., 2018)?

    Here is the abstract:

    Phylogenetic evidence suggests that the invasion and proliferation of retroelements, selfish mobile genetic elements that copy and paste themselves within a host genome, was one of the early evolutionary events in the emergence of eukaryotes. Here we test the effects of this event by determining the pressures retroelements exert on simple genomes. We transferred two retroelements, human LINE-1 and the bacterial group II intron Ll.LtrB, into bacteria, and find that both are functional and detrimental to growth. We find, surprisingly, that retroelement lethality and proliferation are enhanced by the ability to perform eukaryotic-like nonhomologous end-joining (NHEJ) DNA repair. We show that the only stable evolutionary consequence in simple cells is maintenance of retroelements in low numbers, suggesting how retrotransposition rates and costs in early eukaryotes could have been constrained to allow proliferation. Our results suggest that the interplay between NHEJ and retroelements may have played a fundamental and previously unappreciated role in facilitating the proliferation of retroelements, elements of which became the ancestors of the spliceosome components in eukaryotes.

    And here is a particular statement:

    " In some animals, for example, the spliceosome can generate multiple mRNAs through alternative splicings of a single primary transcript, allowing access to additional complexity without a concomitant increase in the amount of coding DNA."


    Link for the paper: http://www.pnas.org/content/early/2018/11/14/1807709115


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  8. Rube Goldberg was a popular cartoon. There's a reason for that. People just love complicated answers to simple problems. Seriously, I think that's a big part of the reason why folks invent things like the G-value paradox.

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  9. I expected that humans have about the same number of genes as other mammals, fish, or insects. For me it's not an issue.

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    1. It wasn't an issue for me either but that's not the point. The point is that it WAS a very important issue for a huge number of scientists - probably a majority.

      Even today, it's still an issue for most of them and that's why they are looking for explanations of what they perceive to be a major paradox.

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    2. The bright side is that their paradox is motivating them to search for a scientific explanation, and it does not feed the Discovery Institute supremacists who inflate their egos with religion then deny that their belief that they are above all else and all others is socially dangerous behavior that leads to bloody wars and genocide.

      https://evolutionnews.org/2018/12/science-article-castigates-human-supremacy/

      The way I see it a genetic system controls cell reproduction and morphology of one cell, but the multicellular morphology that develops is dependent on the cell migration and behavior patterns of the autonomous cells in the colony.

      We have a relatively large (but not largest) brain and can make a wide range of sounds to form words with, yet our lack of a strong tail/flipper and bodily protection makes it impossible to (without technology) survive extreme heat and cold that other animals thrive in. Nor can we fly on our own through water and/or air like most birds can.

      In my opinion what seems like an advantage is for the most part our way of making up for what we morphologically lack at birth. We had to run for clothes, then invent climate controlled environments, or freeze to death.

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    3. I have to add that the chimp versus human scores are controversial, but even where (with enough practice) a human can do as well as a chimp it's none the less a surprise finding.

      In either case: being kicked out of paradise and having to run for clothes after falling is sounding more and more like a fuzzy memory of our evolutionary history.

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  10. Perhaps it is irrational of me, but I would expect the most genetically complex creatures to be those undergoing metamorphosis? Amphibians and some insects would be the summit of the biological hierarchy, which strikes me as an argument against rating organisms by the number of genes?

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