Sunday, January 17, 2016

Origin of de novo genes in humans

We know quite a lot about the origin of new genes (Carvunis et al., 2012; Kaessman, 2010; Long et al., 2003; Long et al., 2013; Näsvall et al., 2012); Neme and Tautz, 2013; Schlötterer, 2015; Tautz and Domazet-Lošo (2011); Wu et al., 2011). Most of them are derived from gene duplication events and subsequent divergence. A smaller number are formed de novo from sequences that were not part of a gene in the ancestral species.

In spite of what you might have read in the popular literature, there are not a large number of newly formed genes in most species. Genes that appear to be unique to a single species are called "orphan" genes. When a genome is first sequenced there will always be a large number of potential orphan genes because the gene prediction software tilts toward false positives in order to minimize false negatives. Further investigation and annotation reduces the number of potential genes.

The human genome has a number of duplicated genes that aren't found in our closest relatives but, for the most part, these are transient duplications and the extra gene will soon be deleted or disabled (it becomes a pseudogene). The interesting new genes are de novo genes—new genes that are not derived from a gene duplication event. There are about 60 potential de novo genes in our genome [see How many genes do we have and what happened to the orphans?].

New potential genes tend to be small and if they have an open reading frame then the potential protein is less that 100 amino acids long. They are usually transcribed at very low levels and often the transcripts are only detected in a few types of tissues; notably, brain or testes. Both of these tissue are famous for having lots of transcripts.

Only a small number of these potential genes will turn out to be actual genes with a functional RNA [What Is a Gene?]. The problem is that it's hard to prove that a potential de novo gene is really a gene (i.e. has a biological function).

Ruiz-Orera et al. (2015) are the latest workers to give it a try. They analyzed the human, chimpanzee, macaque, and mouse genomes for regions that were frequently transcribed to produce a transcript that was at least 300 nucleotides long. This identifies potential genes. They compared the five genomes to find examples that were only expressed in humans and/or chimpanzees but where similar nontranscribed sequences were present in macaque or macaque and mouse genomes.

The result was 634 human-specific transcribed regions, 780 that were chimpanzee-specific, and 1,300 that were only found in humans and chimps. Only 51% of these transcribed regions were found in intergenic regions. The other 49% were found within known genes: 38% within introns and 11% overlapping exons. (Recall that about 70% or our genome is DNA that's between genes [What's in Your Genome?].)

We want to know if these are real genes of just spurious transcripts. The first clue is that 94% of these transcribed regions are expressed in testes. That's a tissue where chromatin is being reformed and DNA is much more exposed than in other tissues. You expect more spurious transcription in testes cells.

These potential de novo genes are not conserved, by definition, so you can't use sequence conservation as evidence of function. Instead, the authors looked for evidence of proteins/peptides encoded by the transcripts. This eliminates all possible genes that may have a functional noncoding RNA but it's a start.

They found one human-specific peptide and 6 hominoid-specific peptides by mass spectrometry. By looking at ribosome-associated RNAs they identified 5 additional human-specific and 10 hominoid-specific transcripts. Thus, there are 21 potential de novo protein-coding genes. The median size of the peptides is 76 amino acid residues.

Next they looked for signatures of purifying selection by comparing the number of substitutions in the transcribed regions in the macaque lineage and the human/chimpanzee lineages. The sequences in the macaque lineage are expected to accumulate mutations at the rate of mutation (neutral rate) but there should be fewer mutations in the human and chimpanzee lineages if the sequences have a new function. They conclude, "... in de novo genes in general there was not a significant decrease in the number of substitutions in the longest ORF when compared to neutrally evolving sequences, suggesting that the majority of these transcripts do not encode functional protein."

The conclusion is that there are very few de novo protein-coding genes in the human genome but,
Our results indicate that the expression of new loci in the genome takes place at a very high rate and is probably mediated by random mutations that generate new active promoters. These newly expressed transcripts would form the substrate for the evolution of new genes with novel functions.
This is important because it shows us that generation of new genes from "random" sequences is not difficult.


Carvunis, A.-R., Rolland, T., Wapinski, I., Calderwood, M.A., Yildirim, M.A., Simonis, N., Charloteaux, B., Hidalgo, C.A., Barbette, J., Santhanam, B., Brar, G.A., Weissman, J.S., Regev, A., Thierry-Mieg, N., Cusick, M.E., and Vidal, M. (2012) Proto-genes and de novo gene birth. Nature, 487:370-374. [doi: 10.1038/nature11184]

Kaessmann, H. (2010) Origins, evolution, and phenotypic impact of new genes. Genome research, 20:1313-1326. [doi: 10.1101/gr.101386.109]

Long, M., Betran, E., Thornton, K., and Wang, W. (2003) The origin of new genes: glimpses from the young and old. Nat Rev Genet, 4:865-875.

Long, M., VanKuren, N. W., Chen, S., and Vibranovski, M. D. (2013) New gene evolution: little did we know. Annual review of genetics, 47:307. [doi: 10.1146/annurev-genet-111212-133301]

Näsvall, J., Sun, L., Roth, J. R., and Andersson, D. I. (2012) Real-time evolution of new genes by innovation, amplification, and divergence. Science, 338:384-387. [doi: 10.1126/science.1226521 ]

Neme, R., and Tautz, D. (2013) Phylogenetic patterns of emergence of new genes support a model of frequent de novo evolution. BMC genomics, 14(1), 117. [doi: 10.1186/1471-2164-14-117]

Ruiz-Orera, J., Hernandez-Rodriguez, J., Chiva, C., Sabidó, E., Kondova, I., Bontrop, R., Marqués-Bonet, T., and Albà, M. (2015) Origins of de novo genes in human and chimpanzee. PLoS Genet, 11: e1005721. [doi: 10.1371/journal.pgen.1005721]

Schlötterer, C. (2015) Genes from scratch–the evolutionary fate of de novo genes. TRENDS in Genetics, 31(4), 215-219. [doi: 10.1016/j.tig.2015.02.007]

Tautz, D., and Domazet-Lošo, T. (2011) The evolutionary origin of orphan genes. Nature Reviews Genetics, 12(10), 692-702. [doi: 10.1038/nrg3053]

Wu, D.-D., Irwin, D.M., and Zhang, Y.-P. (2011) De novo origin of human protein-coding genes. PLoS Genet, 7:e1002379. [doi: 10.1371/journal.pgen.1002379]

55 comments :

  1. You don't know anything about the origins of genes period! Do you think that your "knowing a little about de novo genes" will change the fundamental truth about that fact?

    Just don't give me the "the science doesn't know it, yet so God did it thing". It's bs. It's an excuse that science has not fundamental answers that you can admit to because they are 100% obvious. The ones that can be watered down, you focus on because that is all you have. Pitty!!!

    ReplyDelete
    Replies
    1. Your comments are getting tiresome. If you can't say anything intelligent then don't say anything at all.

      This is your first warning.

      Delete
    2. Larry, Why don't you say that my comments are exposing the lack of knowledge? Do you think that you can just wave it away? What's in your way? I know what it is. I don't care why YOU CHOSE this path, but I have a pretty good idea. You don't enjoy it but you have no choice because there is not way out. So the only way left is to continue deeper in. God-by!

      Delete
    3. Why don't you say that my comments are exposing the lack of knowledge?

      Oh, they're exposing a lack of knowledge all right.

      Say, you wouldn't happen to be able to write down here that slam dunk proof Jerry Coyne was wrong you've mentioned, would you?

      Delete
    4. Eric, go ask one of your handlers to get you your daily dosage of antipsychotics, and restrict your internet access.

      Delete
    5. Eric if this was my blog I would have banned you already. Your pithy comments add about as much to this discussion as my neighbours yappy dog.

      Delete
  2. This is important because it shows us that generation of new genes from "random" sequences is not difficult.

    Yes, in cognitive science the process is called "trial-and-error learning"

    ReplyDelete
  3. This is important because it shows us that generation of new genes from "random" sequences is not difficult.

    Not difficult but not common. I'm supposing changes in the expression of developmental genes would be more common.

    ReplyDelete
    Replies
    1. Since the only genetic changes that can make it to offspring are those that change the gamete cells this part of what Larry said caught my attention:
      The result was 634 human-specific transcribed regions, 780 that were chimpanzee-specific, and 1,300 that were only found in humans and chimps. Only 51% of these transcribed regions were found in intergenic regions. The other 49% were found within known genes: 38% within introns and 11% overlapping exons. (Recall that about 70% or our genome is DNA that's between genes [What's in Your Genome?].)

      We want to know if these are real genes of just spurious transcripts. The first clue is that 94% of these transcribed regions are expressed in testes. That's a tissue where chromatin is being reformed and DNA is much more exposed than in other tissues. You expect more spurious transcription in testes cells.

      Delete
    2. One thing to keep in mind when thinking about de novo gene origins is that genes and the (usually) protein products they encode should not be viewed as singular entities. Many proteins are comprised of an array of structural and functional modules-- a DNA binding domain here, a protein-protein interaction domain there and a histidine kinase domain embedded elsewhere-- in the finished product. Thus, new genes with novel structures and activities can arise by fusion of such modules. It would be interesting to know, then, whether any of the de novo peptides reported by Ruiz-Orera et al. assume an ordered structure after translation. My guess is they don't.

      Delete
    3. This article in New Scientist was interesting

      Science writer Helen Pilcher looks at de novo genes and concludes that most of them code for proteins which are intrinsically disordered. Quoting the article:

      > It was once thought proteins must be folded into a delicate, precise 3D structure to work properly, but it now seems many exist in a state of intrinsic disorder, flitting through thousands of different possible conformations, all the while remaining perfectly functional. About half of human proteins have at least one long intrinsically disordered segment, while 10 percent are disordered from beginning to end.

      > Peter Tompa of the Flanders Institute of Biotechnology in Brussels, who studies intrinsically disordered proteins, suspects that new orphan genes are likely to code for disordered proteins because they are easier to make than folded proteins. And disordered proteins often play a role in cell signalling and regulation. “I wouldn’t be surprised if orphan genes turn out to have regulatory functions,” says Tompa.

      > Perhaps this helps explain why orphan genes can become essential very quickly.

      Delete
    4. @Aceofspades

      Imagine that these regions of DNA were just random pieces that happened to be transcribed and happened by chance to encode an open reading frame of 50-100 amino acids.

      You would expect this subset of potential orphan genes to be a minority of all those regions that are transcribed and that's what you find.

      Furthermore, you expect the encoded peptide to be a random assortment of amino acid residues with no particular structure. That's because random mixtures of amino acids don't usually form alpha helices or beta structures or reverse turns. That's what you see when you look at these peptides.

      There are proteins with regions of SELECTED or SPECIFIED intrinsic disorder but that's a feature, not an accident. Just because such proteins exist is no reason to assume that a random assortment of amino acids must have a function because the peptide has no tertiary structure.

      Delete
    5. @Prof.Moran

      Perhaps you misunderstood me? I wasn't arguing that all (or even most translated sequences have a function). I agree with you that virtually all translated de-novo sequences will have no function. I wouldn't call them de-novo genes in this case because I think the word gene should imply function.

      I wasn't assuming they were functional just because they were disordered. Rather I was talking about the rare cases that could be shown to be functional and then arguing that these would most likely be disordered.

      Delete
    6. From Aceofspades' excellent link:

      All this suggests that it is relatively easy
      for non-coding DNA to acquire the switches
      needed for RNA copies of it to be made. Indeed,
      the ENCODE study found that as much as
      80 per cent of DNA is copied into RNA at least
      occasionally. Some argue that all this RNA
      is functional, but another interpretation is
      that most of this activity is just noise, and that
      junk DNA is routinely transcribed into RNA.

      Proto-genes

      If so, we are basically experimenting with
      thousands of potential new genes all the
      time – and Anne-Ruxandra Carvunis of
      the University of California, San Diego, has
      shown that this is indeed the case, at least in
      yeast. Last year, her team analysed 108,000
      short, unknown but potentially proteincoding
      sequences in the yeast genome
      (Nature, vol 487, p 370). More than 1000 were
      interacting with the cell’s protein-making
      factory, suggesting that they were being
      converted to proteins. “These may just be
      the tip of the iceberg,” says Carvunis.

      Delete
  4. I think this paper shows nicely that very little in evolution is newly invented. Most is modification of existing things.
    It's precisely what you would expect from a combination of random drift and selection in small populations

    ReplyDelete
    Replies
    1. Yes, it's a quite strong refutation of Intelligent Design Creationism. When a car manufacturer decides to add air conditioning to one of its models, they are not limited to trying to cobble it together out of the intake manifold or something. They just add completely new components.

      Delete
    2. Unfortunately many creationists believe that de-novo means that the entire sequence has appeared whole cloth out of nowhere with no possible explanation for where it may have come from.

      That would be truly remarkable!

      I swear I've had to correct this misconception 5 or 6 times already.

      Delete
    3. Since most of them deny the existence of junk DNA, they don't really have any other option regarding the origin of new genes, do they?

      Delete
    4. If you consider the basic chemical elements to be your building blocks, then ALL new things are just rearrangements of existing things. Stuart Kauffman calls this "the adjacent possible".

      Delete
    5. When it comes to genetics, we don't consider "the basic chemical elements" to be our building blocks. The building blocks are the 4 standard nucleotide bases. But even then, we are not talking about single nucleotides here, we are talking about rearranging and modifying sequences of these nucleotides 100+ bases in length.

      Delete
    6. Of course. I was stating a general principle. It can be applied to any level of a hierarchy. One person's building blocks are another person's complex assemblies of smaller building blocks.

      Are you the same AceOfSpades25 who commented on the "Unbelievable" blog entry to the interview of P.Z. Myers and Perry Marshall ? If so, I learned a lot from reading your comments.

      Delete
    7. Just out of interest, what did you learn? That I can be an obnoxious arsehole? ;p I felt like I was hounding Perry a little too much

      Delete
    8. I learned something about genetics and evolution from your comments, just as I learn the same from reading Larry's blog. And you pointed out many errors in Marshall's arguments that I had suspected were there, but it is good to hear them confirmed. I am an engineer, and I am embarrassed by Marshall's pretense at understanding biology. No, I don't think you were too harsh with him. His fallacious twisting of reality tends to either drive people away or invoke harsh words, and then he crows about his opponents not being able to engage him on civil, scientific grounds. You didn't succumb to either, which takes a lot of patience.

      Delete
  5. I can understand wanting to trivialize things like the ENCODE project. But the research will ultimately make or break the idea of most of the genome being relics in an evolutionary museum (junkyard). Even now, some things seem to defy notions of accidental emergence.

    “The work illuminates basic facts about the genome’s 3-D structure, including that it forms around 10,000 loops. It also sheds light on how genome structure influences gene expression, as looping DNA brings promoters and enhancers into close proximity……The researchers further attempted to understand the function of the loops. They confirmed that loops often bring together distant enhancers and promoters and that these pairings often lead to changes in gene expression. Thirty percent of the loops found in a lymphoblastoid cell line (GM12878) were formed by promoters and enhancers coming together, the researchers found.”

    http://www.the-scientist.com/?articles.view/articleNo/41653/title/DNA-Loop-the-Loops/

    ReplyDelete
    Replies
    1. Well you see it seems to be really really complex therefore txpiper can't imagine how it could have evolved therefore magic.

      Delete
    2. This stuff isn't new, I was taught this crap over 8 years ago as if it had been already known for 20 years before that. What new discovery has the ENCODE project made?

      Delete
    3. Ah, txpiper - ask anyone who worked on ENCODE whether he/she thinks it means Intelligent Design is more likely.

      I don't think you'll be too happy with the answer.

      Delete
    4. Aceofspades,

      “it seems to be really really complex therefore txpiper can't imagine how it could have evolved”

      Something like that. Cramming a two meter long nucleotide chain into a cell nucleus is a pretty neat trick, but using the loop architecture itself to manipulate gene expression is quite a utility. I can’t think of anything even remotely similar that could be the result of random accidents. Can you?

      Delete
    5. txpiper

      Your Boeing from a scrapyard type argument isn't going to work here because you're neglected to account for selection.

      For billions of years life got along just fine without DNA coiling like this around histones because DNA was a single stranded structure and was arranged in a ring.

      Later when DNA migrated to the nucleus and adopted a chromosome structure, as it grew, space constraints began exerting selective pressures for proteins to act a spools that would allow it to coil and uncoil to save space.

      These coils naturally bring distant promoters into close contact with other sequences by chance - this was an unintentional outcome of coiling. Over time some sequences could feasibly become reliant on these distant promoters, even potentially losing their proximal promoters if the distant ones were working just as well.

      Your lack of ability to imagine something is a poor argument for supernatural intervention. It is also often referred to as an argument from ignorance and outs considered to be a type of logical fallacy.

      Delete
    6. Aceofspades,

      “DNA migrated to the nucleus and adopted a chromosome structure, as it grew, space constraints began exerting selective pressures for proteins to act a spools that would allow it to coil and uncoil”

      I’m afraid you’ve acquired a distorted view about natural selection. Selection is a result, not a cause. It is a removal process. Selection pressure doesn’t make things happen. It can’t induce cooperative proteins, or influence proteins to act a certain way. You’ve been conditioned to think of selection as some sort of natural (actually supernatural) ethereal force, but that perception is entirely false. Selection is just what happens when inferior or ill-suited organisms are, along with their genes, are removed from a population.
      -
      ” to save space”

      You’re invoking purpose.
      -
      “Your lack of ability to imagine something… ”

      Perhaps I am limited in that regard, and perhaps you are gifted. But theories are supported by evidence, not imagination. If you hypothesize that DNA migrated to the nucleus, or adopted a chromosome structure, or just grew, you have to support your ideas. Just saying something happened does not make it a fact. You can’t fill in the gaps with fantasia. Having said that, I have to admit that your method is wildly popular.

      Delete
    7. txpiper,

      You are the one with the distorted view of natural selection.

      "Selection is a result, not a cause. It is a removal process."
      You're wrong about natural selection here, but even if we assume you are right that selection is a removal process, your statement here does not make logical sense. Selection is certainly a cause, it causes changes in allele frequencies in populations. Of course, the result is a change in allele frequencies in populations, so your distinction here makes no sense.

      "Selection pressure doesn’t make things happen."
      I just explained how it does.

      "It can’t induce cooperative proteins, or influence proteins to act a certain way."
      Of course not. That would imply forethought, and active drive toward a particular goal. Natural selection doesn't do that, and it doesn't need to do that to result in evolutionary change.

      "You’ve been conditioned to think of selection as some sort of natural (actually supernatural) ethereal force, but that perception is entirely false. Selection is just what happens when inferior or ill-suited organisms are, along with their genes, are removed from a population."
      Wrong again. Nothing about natural selection as an evolutionary process requires anything supernatural or ethereal. You have been conditioned to think this way, perhaps. Selection can remove alleles from a population, or increase their frequency. You don't seem to understand even this elemental process.

      "But theories are supported by evidence, not imagination. If you hypothesize that DNA migrated to the nucleus, or adopted a chromosome structure, or just grew, you have to support your ideas. Just saying something happened does not make it a fact. You can’t fill in the gaps with fantasia."

      Actually, evolutionary theory has enormous amounts of evidence to support it. Because it cannot explain (at least currently) how DNA became organized into a nucleus (at least in eukaryotes, of course) it has at least hypotheses consistent with evolutionary theory that scientists are exploring.

      Since you are unsatistifed with this, what is your alternative explanation for the nucleus, and what evidence do you have to support it?

      Delete
    8. Chris B,

      “Selection is certainly a cause, it causes changes in allele frequencies in populations. Of course, the result is a change in allele frequencies in populations, so your distinction here makes no sense.”

      Any way you choose to look at it, natural selection is nothing more than organisms dying. Nothing is really and truly being favored or selected. Selection barely even qualifies as a process as there is no real activity involved. If alleles are preserved or removed, it is because their hosts either survived, or did not survive.

      Aceofspades’ appeal to selection is a great example of how the concept is abused. It is understandable that this happens. Lots of writers and articles tend to leave people with a distorted impression. Here’s a good example:

      “ "When the early toothed whales began to cross the open ocean, they found this incredibly rich source of food surfacing around them every night, bumping into them," said Lindberg, former director and now a curator in UC Berkeley's Museum of Paleontology. "This set the stage for the evolution of the more sophisticated biosonar system that their descendents use today to hunt squids at depth.” “

      http://phys.org/news/2007-09-whales-evolved-biosonar-squid-deep.html

      Do you see the problem? Bumping into food doesn’t set the stage for anything. This guy is just completely screwed up on account of natural selection having become a fairy.

      ——

      “Since you are unsatistifed with this, what is your alternative explanation for the nucleus, and what evidence do you have to support it?”

      I’m a creationist, so my explanation involves intellect capable of conceiving and producing such things. I accept complexity that cannot be the result of accidents as evidence.

      Delete
    9. Tx:
      "I’m a creationist, so my explanation involves intellect capable of conceiving and producing such things."
      Which intellect are we talking about? ET, Odin, Jupiter?

      Delete
    10. txpiper,

      "Selection barely even qualifies as a process as there is no real activity involved."
      Wrong, but in any case irrelevant. Regardless of how you choose to misrepresent it, selection happens and can result in change. Conversely, evidence for an intelligent designer or supernatural being conjuring species out of nothing hasn't a shred of evidence to support it.

      "I’m a creationist, so my explanation involves intellect capable of conceiving and producing such things."
      Ok, provide evidence an 'intellect' produced these things.

      "I accept complexity that cannot be the result of accidents as evidence."
      Arguments from personal incredulity do not constitute evidence. But you fail to even frame the problem properly. Define what you mean by 'accidents'.

      Delete
    11. @txpiper...

      I can't believe I missed your response.

      You're quite right that what I offered was simply a plausible hypothesis. It wasn't based on evidence because like you I haven't yet bothered to look into what the evidence says for the evolution of chromatin looping. There is probably plenty of scientific literature on this out there.

      What you fail to grasp though is that all that is needed to defeat your argument from ignorance is a plausible hypothesis.

      You were arguing that DNA loops are so complex that the only plausible explanation for this is that a magic man (aka God) must have done it.

      All that is needed to defeat this argument is a plausible explanation that doesn't invoke untestable and invisible beings. I offered you a single plausible hypothesis - I don't know whether it is true or whether is is the one that currently has the most support in the scientific literature but a simpler explanation is all that is needed to defeat an argument from ignorance that invokes ntestable and invisible beings.

      Finally, you made the claim that I was invoking purpose when I said "to save space". I wasn't invoking purpose - this was merely shorthand for the idea that:

      - As DNA replicated and grew, the nucleus was becoming crowded
      - Organisms that stumbled upon early histone-like proteins which bound to parts of their DNA compressing it into more of a 3 dimensional structure were at an advantage and so were able to outcompete organisms that had chaotic genomes. Perhaps these other organisms were slower to transcribe genes or were doing so more haphazardly such that cells could not differentiate as effectively.
      - Over time, organisms that couldn't order their nuclear genome were out-competed out by those that could
      - Selection continued acting in such a way as to refine these histones

      You dismiss selection as something incapable of producing novelty - well obviously. No intelligent person has ever claimed this (much to the chagrin of Douglas Axe and Ann Gauger). But when selection is combined with random mutations then it does produce novel solutions. This has been demonstrated time and time again. In my degree, I wrote algorithms which could develop novel solutions to problems based on mutation and selection

      See this
      Or this
      Or this
      Or this

      Or if you prefer biology:
      See this
      Or this
      Or this

      Delete
    12. I’m a creationist, so my explanation involves intellect capable of conceiving and producing such things. I accept complexity that cannot be the result of accidents as evidence.

      Are you a "capital 'c' Creationist," i.e., do you think the universe and life were created by God?

      If you do, then what you wrote above is self-contradictory. Think about it for a minute: "...complexity that cannot be the result of accidents," in a universe that an all-powerful and all-knowing God made, is equivalent to "God could not have made this outcome occur using random mutation, neutral evolution, and selection," or for shorthand, "God could not have made this outcome using evolution." To say that, you're putting limits on God, which means God can't be all-powerful and all-knowing. That contradicts the premise you started with, that the universe and life were created by an all-knowing, all-powerful God.

      You could say perhaps that in your view God didn't choose to use evolution. But then you have no proof, it's only your opinion. As soon as you say you can prove this outcome was impossible via evolution, you are saying it wasn't possible for an all-powerful, all-knowing God to do it, and you've contradicted yourself.

      Delete
    13. This comment has been removed by the author.

      Delete
  6. Great post. I've always been skeptical of claims of de-novo gene discoveries. Even if a few are found, the contribution of duplication to the gene birth-rate still dwarfs de-novo origination. I guess this observation has implications for commonly given definitions of certain types of pseudogenes...

    ReplyDelete
  7. All need to study this:
    http://www.kurzweilai.net/why-evolution-may-be-intelligent-based-on-deep-learning

    This complements all the theory I have that comes from other areas of cognitive science.

    ReplyDelete
  8. The abundant existence of taxonomically restricted genes has been confirmed by several high-throughput sequencing techniques, from Prokarya to Eukarya, and this is another serious problem for evolution.

    "Orphan genes have puzzled scientists since their initial discovery in the infancy of genome biology. Originally thought to be artifacts of sampling bias that would disappear as more genomes were sequenced, "orphan" genes have been found in large numbers in every single prokaryotic and eukaryotic genome that has been sequenced and annotated."

    "The latest analyses have shown that between 10-20% of every sequenced genome is composed of orphan genes (Khalturin et al., 2009), and some predict that this will continue to be the case even as many more genomes are sequenced (Wilson et al., 2005)." (Daniel S. Standage 2013).

    It's interesting to see these genes challenging evolution, which denies that de novo genes would appear "out of thin air", as Fraçois Jacob amde it clear in a 1977 article published at Science:

    "The probability that a functional protein would appear de novo by random association of amino acids is practically ZERO".

    Adi Livnat, citing Jacob, presented the problem for evolution in a very practical way:

    "Other empirical findings have been more directly challenging. Consider for example de novogenes (e.g., [9-13])—genes that presumably have arisen “out of thin air” by a sequence of random mutations that came together into a new functioning gene, including signals for transcription and translation and even alternative splicing [11]. This de novo formation takes place even though traditional natural selection could not have acted on this sequence of mutations until the gene was already complete (substantial enough to be active), in clear contradiction with what Jacob justifiably predicted to be impossible" (A. Livnat Biology Direct 2013,8:24).

    It's claimed that new genes arise from duplication of existing ones, which begs the question, where did the first genes come from? How did they form?

    Wallace Barbosa

    ReplyDelete
    Replies
    1. Hahaha... An opinion from 1977!? You base your belief that denovo genes are impossible on an opinion made in 1977.

      Who the fuck needs evidence when we have opinions from 1977?!

      Delete
    2. I do not believe that anyone is stating that de-novo gene origination does not happen, simply that origination through duplication is much-much-much more common; and that there are probably no examples of de-novo genes in the human genome. Keep in mind, out of the 64 possible codons (4^3), only three code for a stop codon.

      Delete
    3. Just to be clear.. I assume you're talking about genes exclusive to humans and not found in other apes as opposed to genes which appear to have arisen denovo at any point in our distant past? I'm pretty sure there are known examples of these.

      Delete
    4. @Wallace BS, you don't appear to read very thoroughly. From Larry's discussion of the recent article:

      Thus, there are 21 potential de novo protein-coding genes. The median size of the peptides is 76 amino acid residues.

      Next they looked for signatures of purifying selection by comparing the number of substitutions in the transcribed regions in the macaque lineage and the human/chimpanzee lineages. The sequences in the macaque lineage are expected to accumulate mutations at the rate of mutation (neutral rate) but there should be fewer mutations in the human and chimpanzee lineages if the sequences have a new function. They conclude, "... in de novo genes in general there was not a significant decrease in the number of substitutions in the longest ORF when compared to neutrally evolving sequences, suggesting that the majority of these transcripts do not encode functional protein."


      So of 21 potential candidates, less than half may actually be new functional genes. That is from an original pool of 1300 "transcribed regions" found in humans and chimps, 634 additional such regions in humans alone, and 780 in chimpanzees alone. Thus no more than 10 (and possibly zero) of 2700+ candidates, compared to a total of 20,000+ genes in humans and about the same number in chimps.

      So how does a number of 0-10 out of 40-50,000 contradict Jacob's thinking that the chances of de novo genes arising are "practically zero"? (Note he *didn't* say impossible. But it was his thinking they should be quite rare. And this is what we see.)

      Delete
    5. "Just to be clear.. I assume you're talking about genes exclusive to humans and not found in other apes as opposed to genes which appear to have arisen denovo at any point in our distant past? I'm pretty sure there are known examples of these."

      Yes, I believe you follow me.

      There are genes exclusive to humans, but this exclusiveness is generally due to gene loss in other organisms.

      Regarding genes that have arisen de-novo in our distant past: since their origination there have likely (actually there is no likely to it, it is almost a certainty) been multiple duplications that have occurred. Any gene that appears to not have any paralogs appears so because either the paralogs have been lost, or are so divergent they cannot be confidently identified.

      Delete
    6. Ridiculous, Larry blocked my other account so I couldn't post my replies....

      Back to the topic (before Larry blocks me again):

      the existence of thousands of orphan genes is undeniable and fits beautifully into Intelligent Design model, leaving evolution again in the hall of shame.

      Now explain me how the very first genes formed, since you all believe tht everything in biology is copy&paste from existing genes..

      In fact, the first life (LUCA) faces several problems, including the fact that it has to be just as complex as the "modern" free-living organisms, which have genomes ranging from 800 to 1500 ORF's (and 1 million base pairs, as demonstrated by Podar et al 2008)... Less than that number, the cells become unable to live independently, becoming obligate parasites and symbionts, which cannot cope with the external medium and its varying and grievous conditions...

      Wallace Barbosa

      Delete
    7. > Now explain me how the very first genes formed, since you all believe tht everything in biology is copy&paste from existing genes..

      You seem to have a problem with reading comprehension. This article clearly affirms that denovo genes exist and apart from you I haven't seen anyone here argue that they are impossible.

      Delete
    8. re wallace.b.s.88--

      Why do Intelligent Design creationists all seem to think that LUCA was the first life form, not the last COMMON life form?

      Delete
    9. Ridiculous, Larry blocked my other account so I couldn't post my replies....

      Ridiculous. I did no such thing.

      Delete
    10. Sometimes I have trouble with the multi-step process of posting at this blog, and my posts disappear. Sometimes I think I did everything right, but my posts disappear. The first few times I had this problem I thought it was some kind of moderation thing (with a really nutty moderator) and then I realized it's just problems with the process and/or operator error.

      Conclusion: it would be easy to think one's account was blocked here when it wasn't.

      Delete
    11. “Why do Intelligent Design creationists all seem to think that LUCA was the first life form, not the last COMMON life form?”

      I don’t know anyone who thinks that. I do know people who recognize that LUCA’s antecedents seem to defy what is actually known about biological life. The last time I read about it, the minimum number of genes required for an organism to live and reproduce was around 250. And everybody agrees that once upon a time, there were no genes at all.

      Delete
    12. "The last time I read about it, the minimum number of genes required for an organism to live and reproduce was around 250."

      That would be for a free living cell, with a DNA-based genome, a 20 amino acid alphabet and modern protein translation.

      Once you start letting go of these assumptions it becomes clear there might be other possibilities.

      If perhaps it had an RNA-based genome instead of DNA, it would not need the biosynthetic pathways for making DNA monomers. Nor machinery for both RNA and DNA replication.

      If perhaps it only had a smaller amino acid alphabet of 8 to 12 amino acids, it would not need the genes to biosynthesize the additional and yet-to-evolve 8 to 12, nor the corresponding tRNA molecules, not their aminoacyl-tRNA-synthetases.

      If it wasn't free-living it might not have needed a cell membrane, nor the biosynthetic pathways to make phospholipids.

      And so on and so forth.

      I don't claim to know that such an organism ever existed, but what I do claim to know is that it's too soon to declare the search over and to start relegating the unexplained to mythological beings with magic powers that zap things into existence with spells and incantations.

      Think about this analogy. You come to a horse race, to see a horse (naturalism) that has won every race it ever participated in, literally hundreds of thousands of races against all other horses it's ever been put up against (explained millions of phenomena with nothing but blind natural forces).

      It's about to race again, where do you put your money?

      Delete
    13. txpiper

      "The last time I read about it, the minimum number of genes required for an organism to live and reproduce was around 250."

      You have to consider FREE-LIVING ORGANISMS to elucidate what LUCA should seems like..

      The genome size you mentioned is only found in obligate parasites and symbionts. To survive as a fre-living cell, it takes hundreds of essential genes.. Obligate parasites like Mycoplasma can barely survive in nutrient-rich growth medium, which explains why researchers call them "fastidious" cells.

      In any "outdoors" environment, the cells have to cope and deal with many dangerous and changing conditions and sources of stress, such as osmotic shock, oxidation, UV radiation, salt stress, cold and heat stress, nutrient deprivation, toxic substances, etc.. Back to mycoplasma, they lack cell wall, have a very limited metabolic capability, which makes them unable to metabolize all the needed substrates, etc.. That's science again bursting naturalistic assumptions without mercy.

      "And everybody agrees that once upon a time, there were no genes at all."

      That's irrelevant unless you bring confirming data to back that assumption.

      Delete