Monday, November 02, 2015

The birth and death of salmon genes

Modern Salmonidae (salmon and its relatives) have genomes that show clear evidence of an ancient duplication event. Berthelot et al. (2014) sequenced the rainbow trout genome and constructed a phylogenetic tree of all teleost fish. The genome duplication event in the Salmonidae lineage can be dated to approximately 96 million years ago (96 ± 5.5 Mya).

This event provides an opportunity to track the fate of the duplicated protein-coding genes. How many of the original duplicates are left and what happened to them?

There were able to get reliable data on 9,040 of the original genes in the ancestral genome. (That's about one third of the estimated 31,000 genes in the genome of the original species.) Of those 9,040 genes, 4,728 (52%) are now single copy genes because one of the duplicated genes has been lost. Many of these original genes are still detectable as pseudogenes at the right position in the genome.

By combining these results with studies of more ancient genome duplications in the vertebrate lineage, it looks like the average rate of gene loss is about 170 genes per million years (Berthelot et al., 2004). It's likely that in the majority of cases one of the duplicates will eventually become inactivated by mutation and that allele will become fixed in the genome by random genetic drift. (Some early inactivation events may be selected.)

4,312 (42%) of the original duplications have been retained in the trout genome as a small family consisting of two paralogues. In some cases the two paralogues have diverged and in some cases they are expressed in different tissues or at different stages of development. This suggests that the two copies have evolved different functions.

However, most of the duplicated genes seem to be performing similar functions and it's likely that there is no selective pressure to retain two copies. There just hasn't been enough time to inactivate one copy.

The trout genome contains 241 ancient microRNA genes and 233 of them still have two copies, one from each of the duplicated genomes. The authors suggest that this is significant and it indicates that multiple copies on these microRNA genes are needed. I'm not sure if this is true since these genes are quite a bit smaller than the average protein-coding gene so they will take longer to inactivate by mutation.

In any case, the big picture provides us with lots of data on the birth of new genes by duplication and death of genes by pseudogene formation.


Berthelot, C., Brunet, F., Chalopin, D., Juanchich, A., Bernard, M., Noël, B., Bento, P., Da Silva, C., Labadie, K., and Alberti, A. (2014) The rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates. Nature communications, 5:3657 April 22, 2014 [doi:10.1038/ncomms4657]

32 comments :

  1. > By combining these results with studies of more ancient genome duplications in the vertebrate lineage, it looks like the average rate of gene loss is about 170 genes per million years (Berthelot et al., 2004).

    Is that just for genes that are now redundant because duplicates exist? Surely this doesn't apply to all genes since functional sequences that have no backups tend to be conserved?

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    1. Larry refers to the average rate of gene loss following polyploidization events. Clearly, almost all of that loss is of the sort you suggest, but following such an event that category would equal all genes, initially.

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  2. Wait, I thought they were all created on a Thursday about six thousand years ago...

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  3. Hi Lutesuite

    You keep bringing up the "sequence space" and saying that, for the degree of difference between proteins found in chimps and humans, it must be necessary for the genes coding for these proteins to have "worked thru" this sequence space. But that is simply not the case. If two proteins are, say, 95% similar, then it is only necessary that they undergo enough random mutations to account for this 5% difference. Empirical evidence demonstrates that the observed mutation rate can easily account for this.

    Here are my thoughts on this. If both proteins do the same function I completely agree that this could be the result of just mutational activity but what if the functions are different. Given Arts number that the probability of hitting sequencing space is 1/10^10 as a minimum value and 1/10^64 as a maximum value for proteins of 100 amino acids and all these protein mods hit functioning space...how do we explain this as a product of random mutation
    with only 5 x 10^7 tries?

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    1. Art Hunt illustrates how this can happen in Figure 4 of his article. Why are you citing as evidence for your position an article whose whole point is to demonstrate that your position is wrong? And where did that 5 x 10^7 figure come from?

      You are also unaware of the research that has been performed that has actually demonstrated the pathways by which functional proteins have evolved over hundreds of millions of years. (Just because you are ignorant of something does not mean it does not exist.) Some of the best of this, by Joe Thornton, is summarized in the following post from Larry.

      http://sandwalk.blogspot.ca/2009/10/joe-thornton-vs-michael-behe.html

      Do read thru the various links there, especially the last one. You'll find them most helpful IF you take the time to actually understand them. You clearly have not done so with the Art Hunt article you keep citing.

      (BTW, you posted this in the wrong thread.)

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  4. Luitesuite
    Have you read and studied Joe Thornton's work? He claims no evidence for a novel protein forming. Ken Miller sighted his work to me and I studied it carefully. This is just like Dazz sending me the article from the NCSE that drops the mechanism discussion because they are using the Scientific method. I wonder if you guys are really reading closely what you are sighting? Ok you are accusing me of the same misunderstanding of Hunts article and I agree that a slight mod could find a different enzyme reaction based on Thornton's work but I now have found 2 sources that claimed 50 human proteins that are not homologous to chimp proteins. Is it reasonable that there have been 50 gene deletions since the common ancestor and the specie survives this
    ? Is it reasonable that the titin protein that works in a mechanical system with actin and myosin can be shortened by 8% by random deletions and still function given titin is very sensitive to mutations. The 5X 10^7 is 50 million...the number of mutations were talking about in Larry's article. Changed threads because I could not send on the other...maybe over loaded. Your computer password helps protect you from someone breaking into your computer with a random search...how? It uses ordered sequences. Yep...not a good architecture for finding function with random change.

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    1. Have you read and studied Joe Thornton's work? He claims no evidence for a novel protein forming.

      He demonstrates the mechanism by which novel proteins arose from an ancient ancestor, by working backwards from the modern protein to the ancient one. This is evidence for a novel protein forming. You need to read the paper again.

      I now have found 2 sources that claimed 50 human proteins that are not homologous to chimp proteins.

      Source, please?

      Is it reasonable that there have been 50 gene deletions since the common ancestor and the specie survives this

      Obviously. Because here we are (or there are the chimps), happily living without them.

      Is it reasonable that the titin protein that works in a mechanical system with actin and myosin can be shortened by 8% by random deletions and still function given titin is very sensitive to mutations.

      I don't know why you are asking this. You've already been told that the length of titin isoforms in humans alone can vary from 34,350 down to 5,604 amino acid residues. So it seems it is not as "sensitive to mutations" as you claim.

      The 5X 10^7 is 50 million...the number of mutations were talking about in Larry's article.

      Oh, dear. You really don't understand the bare basics. Do you think that is the total number of mutations that have happened, in the entire population of the lineage,. since the divergence from the common ancestor? It isn't. It is just the number of mutations that have become fixed.

      It is becoming clearer why you do not accept evolution. It is because your knowledge of it is severely deficient.





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    2. Joe Thornton how proteins evolve -- how new protein functions can evolve from existing proteins. He provided great evidence for that.

      Humans and chimps have some proteins that are not homologous to proteins in the other species. We know at least two mechanisms for developing completely novel proteins; horizontal gene transfer, and mutations that produce a functional start sequence in a random part of the DNA. We don't know if all or most of the novel proteins in the human lineage actually do anything useful. Some may and I predict that most don't, but this is one of the many subjects that should be (and probably is being) researched.

      We know that organisms can loose some proteins and survive. Consider the human vitamin C gene, for example.

      I know nothing about the titin protein. However, I do know that proteins in general have functional parts that can't be changed much without failure and other parts that can change in sequence and often length with little or no change in protein function.

      Like you, I have trouble with the homonyms cite, sight, and site.

      Why do you keep writing "ordered sequences"? Sequences are ordered by their very nature, so what information do you think you've added with this "ordered"?

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    3. Humans and chimps have some proteins that are not homologous to proteins in the other species.

      My understanding is that these genes were likely just deleted in the human lineage. Bill Cole has trouble accepting this. He doesn't say why. I'm sure his religion has nothing to do with it. Yeah, right.

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    4. Sorry, should say "chimp" above. It's probably hard for Bill Cole to stomach that humans are not special creatures for whom God designed shiny new genes that had nothing to do with those damn dirty apes.

      The idea that gene loss was a major contributor to human evolution remains an intriguing one (Olson 1999; Olson and Varki 2003). Interestingly, ∼50 known or predicted human genes were found to be missing partially or entirely in the chimpanzee genome, and some of these differences were confirmed by PCR or Southern blotting (The Chimpanzee Sequencing and Analysis Consortium 2005). Confirmation of the ancestral state of these loci and reciprocal analysis of genes disrupted exclusively in humans requires additional primate outgroup data and further “polishing” of the chimpanzee genome sequence.

      http://genome.cshlp.org/content/15/12/1746.full

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    5. Lutesuite thanks for finding this: I am interested why you think the above conclusion is true. 50 removed genes from a common ancestor. Do you have any evidence we should expect this? We just assume its true because its the only explanation we can come up with in short order?

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    6. 50 removed genes from a common ancestor. Do you have any evidence we should expect this?

      Yes. You've already been given the evidence on the natural mutation rate. Do you still not understand it?

      We just assume its true because its the only explanation we can come up with in short order?

      No. We accept it is likely true because that is the explanation that is most consistent with the enormous amount of scientific evidence we have accumulated. But, sure, if there's an even better explanation, I'm sure people would be interested in it. Do you have anything in mind?

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    7. No. We accept it is likely true because that is the explanation that is most consistent with the enormous amount of scientific evidence we have accumulated. But, sure, if there's an even better explanation, I'm sure people would be interested in it. Do you have anything in mind?

      I don't, but I think this assumption could be tested.

      When I started to blog with Larry I assumed the chimp to man common ancestor was true. Now I think it is an untested hypothesis. A grad student on this blog found the titin differences.

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    8. When I started to blog with Larry I assumed the chimp to man common ancestor was true. Now I think it is an untested hypothesis.

      Really? So explain this:

      http://www.evolutionarymodel.com/ervs.htm

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    9. I don't, but I think this assumption could be tested.

      Oh, so you got nothing. I'm not surprised.

      How do you propose testing it? I mean, besides the many ways it has already been tested that have been brought to your attention in this discussion.

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  5. Hi Bwilson

    Joe Thornton how proteins evolve -- how new protein functions can evolve from existing proteins. He provided great evidence for that.

    Totally agree: He also stated the origin of a novel protein has never been observed.

    I agree a Gene can get inserted by horizontal transfer but the origin of the gene is still unknown.
    We know that organisms can loose some proteins and survive. Consider the human vitamin C gene, for example.
    I agree but in this case we are talking about 50 changes. Will get source to you and Lukesuite.

    I know nothing about the titin protein. However, I do know that proteins in general have functional parts that can't be changed much without failure and other parts that can change in sequence and often length with little or no change in protein function

    Completely agree and there are 400 pub med articles on titans sensitivity to mutation. Luke suite....the different forms of titin are for different muscle functions like skeletal heart etc. Single mutations can cause heart disease.

    Why do you keep writing "ordered sequences"? Sequences are ordered by their very nature, so what information do you think you've added with this "ordered"?

    A little quirk of mine :-) The existence of these put the random mechanisms of evolutionary theory in doubt for me. Now I see the NCSE is backing off also on identifying a testable mechanism. Richard Dawkins took on the challenge of ordered sequences or sequences in the blink watchmaker. He used the english language to simulate their formation in a 29 character english sentence. When I ran a program similar to his program it solved to problem easily at 29 characters in a few seconds. I ran the program for 3 day with over 100million trials at 80 characters and it could not recreate the original sentence. This program was comparing the sequence to the end goal and making changes as the random changes looked more like the end product which is easier then in evolution. The origin and evolution of the sequences inside DNA is a big challenge.

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    1. Totally agree: He also stated the origin of a novel protein has never been observed.

      Yes. Because no one has lived for the millions of years it would take to observe this. Are you really this stupid?

      agree but in this case we are talking about 50 changes.

      So what?

      Will get source to you and Lukesuite.

      It's OK. I found it. Strangely, the authors have no problem explaining it.

      Completely agree and there are 400 pub med articles on titans sensitivity to mutation. Luke suite....the different forms of titin are for different muscle functions like skeletal heart etc. Single mutations can cause heart disease.

      So if any of those really bad mutations happen, the organism dies, and the mutation goes with it. That still leaves a large number of neutral, or nearly neutral, mutations that can, and have, happened.

      Richard Dawkins took on the challenge of ordered sequences or sequences in the blink watchmaker. He used the english language to simulate their formation in a 29 character english sentence. When I ran a program similar to his program it solved to problem easily at 29 characters in a few seconds. I ran the program for 3 day with over 100million trials at 80 characters and it could not recreate the original sentence.

      Congratulations. You've demonstrated for yourself that evolution is not directed at a specific goal. That's what we've been trying to explain to you.


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    2. So if any of those really bad mutations happen, the organism dies, and the mutation goes with it. That still leaves a large number of neutral, or nearly neutral, mutations that can, and have, happened.

      Do you have any evidence that the deletion of 100 amino acids can be neutral?

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    3. agree but in this case we are talking about 50 changes.

      So what?

      What mechanism are you proposing that is going to delete 50 genes?

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    4. Do you have any evidence that the deletion of 100 amino acids can be neutral?

      They don't have to be deleted all at once.

      What mechanism are you proposing that is going to delete 50 genes?

      Ummm, deletions. What were you expecting?

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    5. Also, to clarify: That 50 genes are present in the human, but not the chimp, genome does not mean there were 50 deletions of entire genes. There could just have been mutations that rendered the genes inactive. IOW, they became junk.

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    6. Bill, again and again you get hung up on how to get to some particular protein via random processes. Ain't gonna happen (probably) -- and that's not a problem. That's not how evolution works. It's not working toward an end goal! It's modifying what exists. (Sometimes even modifying existing DNA sequences in a way that produces a novel, likely minimally functional protein product.)

      Think about a population of minimally functional proto-cell. Has a fragile hydrocarbon membrane, an irregularly functional method of generating a useful chemical form of energy storage, RNA (or something like it) that produces new copies (because RNA just does that) and proteins (ditto) most of which do nothing useful and some of which do useful things inefficiently. The RNA mutates a lot (no editing) and the cell divides irregularly when it gets big enough to pinch off into two cells. Daughter cells tend to break down before reproducing, but some of them do reproduce. Many of the breakdowns are caused by failure of the RNA or proteins to function adequately. (At least nothing is around to eat them before they do.)

      Mutations that lead to more stable information carriers or more functional proteins will cause the cells to survive better or reproduce faster. Lots of variations will occur. Lots of those variations won't work. What happens then? Those cells die.

      Will modern hemoglobin evolve (in the cell lineages that survive)? Probably not. Will some proteins that bind to oxygen reversibly evolve? I think we can be sure they will evolve. Hemoglobin of some kind? Hemocyanin? Some third option I don't know about? Something(s). And the great majority of these proteins will have a long ancestry of somewhat different, more or less functional proteins, perhaps doing quite different things. (That's what Thornton's experiments are about.)

      Is your calculation about the probability of randomly generating hemoglobin, or making some chosen sentence, of any relevance here? Not really. Of course the probability of evolving any one long protein is very, very low! However, evolution isn't aiming at any one target. It's just a mechanism for refining and improving* existing organisms, and that can lead to creatures as weird as redwoods and sea slugs and dinosaurs, even humans.

      * improving = producing organisms that are better at producing offspring that will produce more offspring.

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    7. Lukesuite
      Larry's explanation is exon deletion of 100 amino acids 25 times from the common . I want to meet the common ancestor...:-)

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    8. Some third option I don't know about?

      Chlorophyll (substitute magnesium for iron).

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    9. Larry's explanation is exon deletion of 100 amino acids 25 times from the common.

      For what? The 50 missing genes? That's not what he was talking about.

      Anyway, I don't know how commonly deletions of 100 AA's happen, nor whether Larry was saying they happened in chunks of 100 each time. Maybe ask him.

      BTW, my name here is "lutesuite". And here's handy guide to HTML codes to help make your posts more legible:

      http://www.w3schools.com/tags/

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    10. Do you have any evidence that the deletion of 100 amino acids can be neutral?

      Average human mutation rate per generation is 130. And we tend neither to croak in droves nor to turn into super- men and women. Thus 130 genetic modifications per generation in each of billions of people is conclusively demonstrated to be neutral.

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    11. Sorry lutesuite thanks for the guide....hopefully this old dog can learn something :-)

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  6. Hi Bwilson
    I know the theory and believed all of it until a year ago. The sequences are a big problem for finding function. They get bigger then resources can make it through them. As I said before we use sequences as a tool to block random search. I think the unguided story has a double edge sword. As you move further along in evolution you start needing specificity. This is exactly the titin problem with the chimp to man hypothesis. You need 2500 new amino acids ordered that are compatible with the chimp gene or you need to say the chimp was a reduction from the common ancestor. Either explanation is problematic. Also if you look at the architecture of the muscle proteins you can see that there needs to be compatibility between actin myosin and titin. Thats why I think isolated mutations of titin( a molecular spring that connects myosin to the z bar) are so problematic.

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    1. Evolution needs variation and sampling, either random (drift) or non-random (some form of selection). The selection can certainly be unguided, because there's no particular place (as folks have tried to tell you repeatedly, apparently without effect) it's going. And that's it. No need for "specificity," for particular amino acids to change, no need at all for any movement toward any particular goal. Wherever you happen to wind up, well that's where you are, as they say.

      What are the chances a raindrop will take the precise path it does down your windowpane? Does this cause you to doubt gravity, surface tension, etc., in favor of "guided precipitation"?

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    2. Would there be mutations among the titin gene the descendants of the last common ancestor of chimps and humans? Yes. Would some, perhaps even most of them be fatal? In such an important gene, yes. What would happen as a result? Those embryos / fetuses / infants would die.

      Would some of the mutations be survivable? Variation in titin genes among species indicates that some of them would be.

      I don't see a problem for evolution here.

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    3. Hi bwilson

      Would some of the mutations be survivable?

      I think they would all need to be and with myosin and actin making changes along with titin so the mechanism continues to work. I think this creates a challenge to the theory.

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    4. Why do you feel that it's important that no embryos in the lineage of humans or chimps could have had fatal mutations in the titin gene?

      It is true that all mutations in organisms that actually became ancestors of humans and chimps must have been survivable; otherwise there would be no humans and/or no chimps. However, why wouldn't it be possible, for example, for an embryo that might have been your great-great-great-great-great-great-great aunt to have had a fatal mutation in the titin gene?

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