Genetic load and junk.

Mung, to petrushka, elsewhere:

Everyone does not understand “genetic load” and those that do claim to understand are probably wrong. Why don’t you start an OP on genetic load and the genetic load argument? That would be interesting. Betting you won’t.

This is such an OP. I believe the genetic load argument*** was initially proposed by Susumu Ohno in 1972, whose paper also introduced the then-scare-quoted term “junk”. It’s brief, accessible, and worth a read for anyone who wishes to offer an opinion/understand (not necessarily in that order).

The short version: sequence-related function must be subject to deleterious mutations. Long genomes (such as those of most eukaryotes) contain too many bases for the entire genome to be considered functional in that way, given known mutation rates. The bulk of such genomes must either have functions that are not related to sequence, or no function at all.

Interestingly, the paper is hosted on the site of an anti-junk-er, Andras Pellionisz, a self-promoting double-PhD’d … er … maverick. Also of interest is that, contrary to some ID narratives, the idea was initially resisted by ‘Darwinists’, if that term is understood not as people who simply accept evolution, but as people who place most emphasis on Natural Selection. Perfectionism is not the sole preserve of Creationists.

More recent work has characterised the nonfunctional fraction, and this lends considerable empirical support to Ohno’s contentions.

[eta: link to comment]
***[eta: in relation to genome size, not the first time anyone, ever, discussed genetic load!]

209 thoughts on “Genetic load and junk.

  1. There is much more material about Remine’s argument in other places: his own web pages, the debates at sci.bio.evolution accessed through Google Groups.

    Too bad that ARN’s discussions have vanished. I looked for them in the Wayback Machine (achive.org) and found only ARN’s front pages archived, but their forums seem to have been blocked from being archived by a robots.txt file, which is a way of preventing a web-crawling “bot” from accessing pages.

    I can post more links but that should be a new thread. This one is for discussing the junk DNA issue.

  2. I find it very interesting that Larry Moran doesn’t consider the authors of the Human Genome Project to be knowledgeable scientists.

    Very Interesting.

  3. petrushka: The point I made in the other thread and which seems to have been rejected by mung and colewd is that if the sequence isn’t conserved, and any sequence seems to be as viable as any other, than maybe the sequence has no function.

    There are more rigorous arguments than this, but it’s a starting point for discussion.

    What Darwinian process creates conserved DNA sequences?

  4. Joe Felsenstein: There is much more material about Remine’s argument in other places: his own web pages, the debates at sci.bio.evolution accessed through Google Groups.

    Indeed. I came across a lot of material. It does seem to tail off after 2007, though. Not sure if anyone here feels Remine’s arguments have not already been adequately addressed. If they do, they are welcome to put up an OP. (anyone wishing to publish an OP who doesn’t already have the ability to compose and publish – this is available on request)

  5. Alan Fox: Selection.

    Do you think that is science Alan?

    What exactly is the proposition, that if you have SOME genes that are great at copying perfectly every time, and if those genes are related to functions that are useful, then those genes will be selected. Other genes, that are less important, THEY can be bad at copying, because it doesn’t matter, but the important ones, they should be good at it, overtime, those players will reproduce better.

    How many ways can you think of, of how illogical this proposition is? I can think of a whole lot. Here are just a couple:

    -WHAT exactly is the mechanism that makes some genes good at copying, and some bad?

    -Why are there still some genes that cause bad consequences because they mutate, if there is a mechanism that would prevent them from making bad copies.

    -Was there a time in history when ALL genes were bad at copying, and then a MUTATION made them good at copying?? What kind of random mutation does that?

    -How long would it take the mutation which makes genes that are bad at copying become good at copying, drift throughout the entire population?

    -Is the mutation that makes genes good at copying themselves flawlessly, itself subject to a mutation, or is that mutation also conserved?

    -At some point were there deleterious mutations that got a mutation that made them highly conserved, but because they were deleterious, the highly conserved aspect of that gene never drifted throughout the population?

    -Is it only a matter of time before the genes which prevent people from getting heart disease and cancer and diabetes, and that turns off aging in cells, that THESE genes will get the accidental mutation which makes them stable, and then this will drift throughout the populations of the world? How long do you think that will take.

    -Will all living things be immortal one day?

    But here is the biggest logical problem Alan. The claim of evolution is that the entire reason we have diversity and complex intricate, perfectly tuned structures is precisely because gene copying is unstable, if it were stable we never would have gotten the great advances in systems that we see. EXCEPT for when we need stability. How convenient. We have just added another great layer of blind incredulity required to accept the premise of the theory. Its unstable and stable, that is why it works. If it were anyway else it wouldn’t work.

    Sounds like we also need to accept the infinite universes theory, so we won’t be boggled down by the incredible odds needed for this.

  6. phoodoo: Do you think that is science Alan?

    I think that how the organism, and the population carrying the gene pool, interacts with the environment, differential reproduction depending on individual fitness in the niche, is a very plausible and testable explanation for adaptation.

  7. phoodoo: What exactly is the proposition, that if you have SOME genes that are great at copying perfectly every time, and if those genes are related to functions that are useful, then those genes will be selected.

    This is garbled. There are two elements to evolution; variation and selection. There may be sections of some genomes that are more prone to variation but variation in the form of new mutations, crossing over, duplications and so on, are not prescient. Selection is the process that determines whether new alleles spread or disappear.

    Other genes, that are less important, THEY can be bad at copying, because it doesn’t matter, but the important ones, they should be good at it, overtime, those players will reproduce better.

    Copying errors are considered to be a major contributor to variation. But too much variation can lead to extinction. Whether genes spread or disappear depends on how they contribute to an individual’s fitness in the niche that individual inhabits. Good or bad at copying? Where does this come from?

    How many ways can you think of, of how illogical this proposition is? I can think of a whole lot. Here are just a couple:

    M’kay.

    -WHAT exactly is the mechanism that makes some genes good at copying, and some bad?

    There’s a presumption here that’s unsupported. The accuracy of DNA copying from cell to cell is (for me) amazing. You only have to look at Lenski’s LTEE to be amazed how little things change over generations.

    -Why are there still some genes that cause bad consequences because they mutate, if there is a mechanism that would prevent them from making bad copies.

    Which is it. Copying is too accurate – or not accurate enough? Maybe it’s just right.

    -Was there a time in history when ALL genes were bad at copying, and then a MUTATION made them good at copying?? What kind of random mutation does that?

    I’m sure there was a time when replication was less accurate. That’s what selection does. In a race for resources, the better exploiters win out.

    -How long would it take the mutation which makes genes that are bad at copying become good at copying, drift throughout the entire population?

    I’m a skeptic on drift.

    -Is the mutation that makes genes good at copying themselves flawlessly, itself subject to a mutation, or is that mutation also conserved?

    Selection acts on the whole organism (or on it’s extended phenotype) – not on individual genes.

    -At some point were there deleterious mutations that got a mutation that made them highly conserved, but because they were deleterious, the highly conserved aspect of that gene never drifted throughout the population?

    I’m trying to read this charitably but it makes little sense. Genes that are basic to the cell biochemistry are the ones that show the deepest homology and the ones under purifying selection.

    -Is it only a matter of time before the genes which prevent people from getting heart disease and cancer and diabetes, and that turns off aging in cells, that THESE genes will get the accidental mutation which makes them stable, and then this will drift throughout the populations of the world? How long do you think that will take.

    Because human populations are huge and mobile and to a varying extent insulated from selection pressures (such as plague and famine) that were much more prevalent in the past, selection may not exert the same pressure on human populations that it has in the past.

    -Will all living things be immortal one day?

    I doubt it. How boring would that be!

    But here is the biggest logical problem Alan. The claim of evolution is that the entire reason we have diversity and complex intricate, perfectly tuned structures is precisely because gene copying is unstable, if it were stable we never would have gotten the great advances in systems that we see. EXCEPT for when we need stability. How convenient. We have just added another great layer of blind incredulity required to accept the premise of the theory. Its unstable and stable, that is why it works. If it were anyway else it wouldn’t work.

    I don’t claim evolution is a comprehensive explanation for the diversity of life. But I don’t know of another that even approaches “plausible as far as it goes”.

    Sounds like we also need to accept the infinite universes theory, so we won’t be boggled down by the incredible odds needed for this.

    As it is a non-disprovable hypothesis, we are free to pick on that.

  8. Alan Fox: Good or bad at copying? Where does this come from?

    Do you even get what the concept of conserving genes must mean Alan? It means that the genes are conserved by virtue of being good at copying themselves, without mutating. Conservation of a gene type is just another one of those misleading evolution terms they use (like when we say it evolved for a purpose…), when all it really means is the gene doesn’t suffer from copying errors.

    Now exactly HOW a gene is good at copying itself, and how others genes are less good at this (in other words, they are more prone to errors during the copying- you know, what we call mutation!) well, why quibble over little details…

  9. Alan Fox: I’m trying to read this charitably but it makes little sense.

    Actually, until you can explain how in the world the genes are conserved, nothing makes sense.

    But my questions regarding the logic of it all make perfect sense, its just that you are not getting the implications of your suggestion (that selection “chooses” genes that are conserved. Oh boy!).

  10. Alan Fox,

    I don’t claim evolution is a comprehensive explanation for the diversity of life. But I don’t know of another that even approaches “plausible as far as it goes”.

    Thank you 🙂

  11. phoodoo: Do you even get what the concept of conserving genes must mean Alan? It means that the genes are conserved by virtue of being good at copying themselves, without mutating.

    All DNA sequences are inherently “good” at producing copies of themselves. PCR and DNA finger-printing would not work otherwise. That it is almost perfect rather than utterly perfect allows mutations to occur (not to mention high energy ER and other mutagens).

    Conservation of a gene type is just another one of those misleading evolution terms they use (like when we say it evolved for a purpose…), when all it really means is the gene doesn’t suffer from copying errors.

    You have this wrong. A gene is conserved when it is essential to the function of the organism – so essential that almost any mutation will be deleterious, leading to such mutations being eliminated by selection.

    Now exactly HOW a gene is good at copying itself, and how others genes are less good at this (in other words, they are more prone to errors during the copying- you know, what we call mutation!) well, why quibble over little details…

    You seem to be falling under a significant misunderstanding here. Copying or replication is a property inherent in the chemistry of DNA strands. It happens in vitro. Whether copying is accurate is irrelevant to what information is carried by the strand. Junk DNA copies just as accurately as essential genes. It is the selection process that conserves sequences.

  12. phoodoo: Do you even get what the concept of conserving genes must mean Alan?It means that the genes are conserved by virtue of being good at copying themselves, without mutating.

    I’m curious where you’re getting this notion from, phoodoo. That is absolutely not what evolutionary conservation means.

  13. Alan Fox,

    No Alan!, we are not talking about conserving the entire genome! We are talking about conserving certain parts of the genome, whilst other parts are subject to random mutations. The question is how are there specific sections protected from copying errors.

    You are the one who has the misunderstanding.

  14. phoodoo:
    Alan Fox,

    No Alan!, we are not talking about conserving the entire genome!

    I wasn’t, that’s for sure. I’m not sure what you are claiming

    We are talking about conserving certain parts of the genome, whilst other parts are subject to random mutations.

    Conservation of sequences is a result of selection. Selection retains essential genes. Junk sequences, on the other hand are not visible to selection.

    The question is how are there specific sections protected from copying errors.

    Copying errors that occur in essential sequences are likely to be deleterious (if not immediately fatal) and will be selected against and eliminated from the gene pool. Copying errors (and other types of variation) occur randomly. They can occur in conserved sequences and in junk sequences. Selection will weed out deleterious mutations in essential genes. Selection will ignore mutations in junk sequences.

    You are the one who has the misunderstanding

    I may be misunderstanding your point, perhaps.

  15. keiths,

    Oh fucking hell, here goes keiths again with his cut and paste Wikipedia hail mary play which he hopes will solve everything.

    How you read the Encyclopedia Britannica yet Keiths?

  16. Conserved sequences are not protected from copying errors. Copy errors still occur, even in conserved sequences.

    Do I get a star?

  17. For all I know conserved genes are not 100% conserved in terms of sequence similarity, so they can take some variation while still performing their function just fine. Of course mutations still happen in those genes and phoodoo is clueless as usual

  18. Mung: Conserved sequences are not protected from copying errors.

    The definition of conserved is that copy errors have not occurred.

    Conserved sequences are not necessarily functional.

  19. petrushka,

    petrushka: The definition of conserved is that copy errors have not occurred.

    Conserved sequences are not necessarily functional.

    It’s not that they didn’t occur, which seems to be what phoodoo believes. It’s that when they occur they are strongly selected against, don’t reach high frequencies and are therefore infrequently observed.

  20. Mung,

    I think for those who don’t yet realize that there are some regions of the genome that are more susceptible to mutation than others, they should go read a book.

  21. What I would like to see is evidence that specific areas of the genome are immune to copy errors.

  22. Mung,

    Oh well, if you want evidence,you better not hang around evolutionary biologists circles, because they rarely have time for such trivialities, while they are making up their fairy tales.

    Nonetheless, in the world of speculation that is evolution, there is this:

    “The work presented by Lehner and Supek sheds new light on a process that was unexplored – what makes some parts of the human genome more vulnerable to damage? “We found that regions with genes switched on had lower mutation rates. This is not because less mistakes are happening in these regions but because the mechanism to repair them is more efficient”, explains Ben Lehner, group leader, ICREA and AXA professor of risk prediction in age-related diseases at the EMBL-CRG Systems Biology unit in Barcelona. The ‘mismatch repair’ cellular machinery is extremely accurate when copying important regions containing genes that are key for cell functioning, but becomes more relaxed when copying less important parts. In other words, there appears to be a limited capacity for DNA repair in our cells, which is directed where it matters most.”

  23. phoodoo,

    The full text of the paper discussed in the Science Daily article phoodoo quotes from can be found here.

    I’m aware that there is cellular machinery that detects and corrects “mis-matches” following DNA replication. I wasn’t aware that there is new evidence to suggest that such machinery “targets” particular sequences, so thanks for pointing it out. Cheap and fast genome sequencing is producing more results than it is possible to keep up with.

    I’m also aware that some regions of the genome are more prone to mutations than others.

    On the other hand, there is a distinction to be made between DNA mutation and DNA damage repair. Damage can be single or double strand breaks which may be repaired by repair enzymes. Once a mutation such as a base substitution occurs in a strand which replicates, that mutation is invisible to repair enzymes.

  24. phoodoo’s error is to think that conserved sequences are created by repair mechanisms. They aren’t, because even the best repair mechanisms aren’t perfect. Some errors will go unrepaired.

    What creates conserved sequences is purifying selection. Errors still happen, but they are rejected by means of selection.

    Not all errors are rejected even then, because some are neutral. In a protein-coding gene, for example, a portion of the amino acid sequence may be conserved even while the nucleotide sequence allows for synonymous substitution errors.

    Less fulmination and more self-education please, phooster.

  25. petrushka: The definition of conserved is that copy errors have not occurred.

    I agree with Dave Carlson, here. Conserved DNA is as prone to copying errors/mutations as junk but is then subject to purifying selection whereas junk DNA is invisible to selection.

  26. keiths: Less fulmination and more self-education please, phooster.

    ROFL. As if the phoozie is even superficially familiar with the basics.

  27. phoodoo: What Darwinian process creates conserved DNA sequences?

    Natural selection. LOL. How in the hell is this not something you know?

  28. As if the Wikipedia authors are mistaken about conserved sequences and selection, but everyone else knows better.

    You’re a hoot, phoo.

  29. Rumraket,

    Natural selections means things die at different rates. That you would believe that this can create something, other than the artifacts of death, is not surprising.

  30. From bitesizebio.com. Open wide, phoodoo:

    How To Identify Conserved Elements In Genes

    Conserved elements are stretches of DNA sequence that are under purifying selection. That means mutations leading to a change of function in this part of the DNA are detrimental to the organism and will not become fixed in the genome, but rather discarded by natural selection.

  31. keiths,

    That’s a totally flawed definition keiths. Its like saying, well, we have these sequences, so they must have been the most useful, and we don’t have these sequences, because they have been purified. Like I said to Alan, you believe that is science? Only if science requires nothing more than speculation.

    Its even more useless, because in every case where there ARE differences in genes sequences between different species, you simply say, “Well, I guess the mutations must not have been detrimental…”

    Back to the same old circular nonsense of the term fitness.

    But cut and paste all you like keiths. Its just leaves so much more of the rest of the world for others to see.

  32. phoodoo,

    Its even more useless, because in every case where there ARE differences in genes sequences between different species, you simply say, “Well, I guess the mutations must not have been detrimental…”

    Do you think that unreasonable?

  33. Alan Fox: I agree with Dave Carlson, here. Conserved DNA is as prone to copying errors/mutations as junk but is then subject to purifying selection whereas junk DNA is invisible to selection.

    Sloppy writing strikes again. Errors will always occur, but not necessarily be fixed.

  34. phoodoo,

    What is your explanation for differentials in the extent of species differences at various points along the genome?

  35. Allan Miller: differentials in the extent of species differences

    Sorry I don’t understand this sentence.

    Are you asking why do different species have different genomes?

    I think a more interesting question for evolutionists is this, why does a water flea have more genes than any other animal? Nearly 10,000 more than humans.

  36. phoodoo,

    Sorry I don’t understand this sentence.

    Are you asking why do different species have different genomes?

    No, I’m asking why the same groups of species differ more in some genes then others. The evolutionary explanation which you summarily dismiss is that the different genomic regions have been subject to different intensities of purifying selection. So what’s your alternative explanation?

    I think a more interesting question for evolutionists is this, why does a water flea have more genes than any other animal? Nearly 10,000 more than humans.

    More junk DNA. I think you could have probably anticipated the evolutionary explanation yourself without needing it spoon fed.

  37. phoodoo:
    “The work presented by Lehner and Supek sheds new light on a process that was unexplored – what makes some parts of the human genome more vulnerable to damage? “We found that regions with genes switched on had lower mutation rates. This is not because less mistakes are happening in these regions but because the mechanism to repair them is more efficient”, explains Ben Lehner, group leader, ICREA and AXA professor of risk prediction in age-related diseases at the EMBL-CRG Systems Biology unit in Barcelona. The ‘mismatch repair’ cellular machinery is extremely accurate when copying important regions containing genes that are key for cell functioning, but becomes more relaxed when copying less important parts. In other words, there appears to be a limited capacity for DNA repair in our cells, which is directed where it matters most.”

    Is there some reason you wouldn’t expect that based on evolutionary theory? It makes sense that DNA repair of more essential sections of the genome would be selected for more strongly than repair of nonessential sections.

  38. IMO too much emphasis has been placed on DNA as a double strand of bases which are altered by forces known and unknown. There is vastly more to the evolution of life than this unrealistic, simple model. Bare DNA strands do not get passed on through the generations, cells and cellular structures do. And it is becoming increasingly obvious that these structures, down to the structure of DNA itself play an important role in replication and its products.

    Here is one example of this finding.

    Recent work has demonstrated that substantially more territory in the human genome is under selection for maintaining DNA shape than for the exact sequence of nucleotides. This work showed that segments in the human genome that are DNA shape-constrained encompass a substantial fraction of experimentally determined functional regions (enhancers, deoxyribonuclease I hypersensitive sites, promoters, etc.), evidence that maintaining DNA shape is important to at least some aspects of genomic function.

    It is easy to envision accidental mutations occasionally having a beneficial effect on a single nucleotide code. But when we start to see multiple and interlacing codes and constraints, accidental beneficial changes become increasingly unlikely to produce anything substantial. It becomes more like solving a multi-dimensional Rubik’s cube than solving an anagram of a four letter word.

    Some portions of the genome that are considered of no importance due to the fact that their sequences are seen to have no meaningful conservation may in fact actually possess structural conservation. Focusing solely on genomic sequences does not reflect reality, it only reveals our myopia.

    And what of the products of the evolutionary process, the organisms themselves. Studying biomes such as tropical rain forests demonstrates the power of natural selection. The numbers of species which make up these environments is vast, but most of them have been reduced to being able to exist in extremely narrow niches which are evolutionary cul-de-sacs. Natural selection produces short term benefits at the expense of long term viability.

  39. CharlieM,

    The cells and everything in them are manufactured from sequences held in DNA – including DNA itself. This one has been done to death.

    No-one focusses solely on DNA sequence. That’s a ludicrous straw man.

  40. Patrick: Is there some reason you wouldn’t expect that based on evolutionary theory? It makes sense that DNA repair of more essential sections of the genome would be selected for more strongly than repair of nonessential sections.

    The DNA repair is selected for? So you mean some individuals have bodies that had used DNA repair for nonessential sections of DNA (now we had to say bodies, because we can’t say had a genome which repaired its genome, right? Its a new mystery where this ability is being stored.) but they reproduced less than those that had bodies which had DNA repair that repaired what was useful to repair.

    So every once in a while we get bodies which repair genomes anywhere, we also get bodies which don’t repair anywhere, and we also get bodies which repair their entire genome, but none of those other options fare as well in the reproducing arena as the bodies which repair their genomes “just right!” and so those are the ones that drift throughout the population.

    This natural selection gets more amazing every day! Or actually its not that natural selection is amazing, its that there are infinite universes, so everything is possible in some universe, we just happen to be in the one where the really, really, really incredible happens.

  41. CharlieM,

    I think this is a great post and you are spot on with the impossibility of something random creating anything out of this complexity.

    I strongly disagree with Allan’s casual hand-waving away of this problem.

  42. CharlieM: But when we start to see multiple and interlacing codes and constraints, accidental beneficial changes become increasingly unlikely to produce anything substantial.

    Why? You claim it here, but no argument follows. Explain why you think it is so, and then back it up with concrete real-world experiments.

    Phoodoo is very impressed with mere assertion, I’m not. Why does the fact that DNA is in interaction with the intra and extracellular environment (and that to understand the organism fully, we must understand these interactions) make evolution less probable? Why?

    CharlieM: Some portions of the genome that are considered of no importance due to the fact that their sequences are seen to have no meaningful conservation may in fact actually possess structural conservation.

    They may, but DO they? Why to they vary so much between even closely related and pretty much identical species? Why can one species of water-lice, pretty much morphologically and behaviorally identical to another species of water-lice, get by with ONE TENTH the amount of DNA of it’s cousin?

    CharlieM: Focusing solely on genomic sequences does not reflect reality, it only reveals our myopia.

    Nobody focuses SOLELY on genomic sequences. One might put an EMPHASIS on genomic sequence data for various reasons, that doesn’t mean one is not aware there’s more to the equation than sequence.

    CharlieM: And what of the products of the evolutionary process, the organisms themselves. Studying biomes such as tropical rain forests demonstrates the power of natural selection. The numbers of species which make up these environments is vast, but most of them have been reduced to being able to exist in extremely narrow niches which are evolutionary cul-de-sacs. Natural selection produces short term benefits at the expense of long term viability.

    Yes, of course, evolution can’t peer into the future, it can only adapt living organisms to their current circumstances. This isn’t an argument against the possibility of evolution at all.

  43. CharlieM: And it is becoming increasingly obvious that these structures, down to the structure of DNA itself play an important role in replication and its products.

    What determines the structure and shape of DNA? That’s right, sequence.

  44. phoodoo,

    I strongly disagree with Allan’s casual hand-waving away of this problem.

    And I strongly disagree with your causual hand-waving of my casual hand-waving away of this … problem? Why is it even a problem? Theoretical 3D regulation and the inheritance of primary sequence are entirely compatible.

    What science are you actually basing your enthusiasm for Charlie’s view on? Other than that he comes from the same ‘side’? What persuades you that the unproven possibility of 3D regulation means that primary sequence is somehow relegated to a mere supporting role?

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