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Human proteome more complex “than previously thought.” Surprise us again.

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From The Scientist :

There may be more to the human proteome than previously thought. Some genes are known to have several different alternatively spliced protein variants, but the Scripps Research Institute’s Paul Schimmel and his colleagues have now uncovered almost 250 protein splice variants of an essential, evolutionarily conserved family of human genes. The results were published today (July 17) in Science.

Focusing on the 20-gene family of aminoacyl tRNA synthetases (AARSs), the team captured AARS transcripts from human tissues—some fetal, some adult—and showed that many of these messenger RNAs (mRNAs) were translated into proteins. Previous studies have identified several splice variants of these enzymes that have novel functions, but uncovering so many more variants was unexpected, Schimmel said. Most of these new protein products lack the catalytic domain but retain other AARS non-catalytic functional domains.

“The main point is that a vast new area of biology, previously missed, has been uncovered,” said Schimmel. More.

What say we copyright the expression “than previously thought”?

We won’t charge anybody to use it, but after it’s been used five times in a publication like The Scientist , we’ll insist that they write an editorial explaining why they haven’t come to expect this by now.

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9 Replies to “Human proteome more complex “than previously thought.” Surprise us again.

  1. 1
    bornagain77 says:

    Although they tried to put a Darwin friendly spin on this finding towards the end of the article, finding 250 protein splice variants of a human gene(s) is very antagonistic to Darwinian presuppositions. When alternative splicing was first discovered in a virus it caused quite a stir and was thought to be some type of a fluke or a mistake since the odds against getting several messages from one sequence by accident are statistically zero. But now, despite the fact that Darwinists did not expect such an astonishing level of data compression in the genome, alternative splicing is found to be ‘typical’,,,

    The Extreme Complexity Of Genes – Dr. Raymond G. Bohlin – video

    Multiple Overlapping Genetic Codes Profoundly Reduce the Probability of Beneficial Mutation George Montañez 1, Robert J. Marks II 2, Jorge Fernandez 3 and John C. Sanford 4 – published online May 2013
    Excerpt: In the last decade, we have discovered still another aspect of the multi- dimensional genome. We now know that DNA sequences are typically “ poly-functional” [38]. Trifanov previously had described at least 12 genetic codes that any given nucleotide can contribute to [39,40], and showed that a given base-pair can contribute to multiple overlapping codes simultaneously. The first evidence of overlapping protein-coding sequences in viruses caused quite a stir, but since then it has become recognized as typical. According to Kapronov et al., “it is not unusual that a single base-pair can be part of an intricate network of multiple isoforms of overlapping sense and antisense transcripts, the majority of which are unannotated” [41]. The ENCODE project [42] has confirmed that this phenomenon is ubiquitous in higher genomes, wherein a given DNA sequence routinely encodes multiple overlapping messages, meaning that a single nucleotide can contribute to two or more genetic codes. Most recently, Itzkovitz et al. analyzed protein coding regions of 700 species, and showed that virtually all forms of life have extensive overlapping information in their genomes [43].

    38. Sanford J (2008) Genetic Entropy and the Mystery of the Genome. FMS Publications, NY. Pages 131–142.
    39. Trifonov EN (1989) Multiple codes of nucleotide sequences. Bull of Mathematical Biology 51:417–432.
    40. Trifanov EN (1997) Genetic sequences as products of compression by inclusive superposition of many codes. Mol Biol 31:647–654.
    41. Kapranov P, et al (2005) Examples of complex architecture of the human transcriptome revealed by RACE and high density tiling arrays. Genome Res 15:987–997.
    42. Birney E, et al (2007) Encode Project Consortium: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816.
    43. Itzkovitz S, Hodis E, Sega E (2010) Overlapping codes within protein-coding sequences. Genome Res. 20:1582–1589.

    Landscape of transcription in human cells – Sept. 6, 2012
    Excerpt: Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.,,,
    Isoform expression by a gene does not follow a minimalistic expression strategy, resulting in a tendency for genes to express many isoforms simultaneously, with a plateau at about 10–12 expressed isoforms per gene per cell line.

    Time to Redefine the Concept of a Gene? – Sept. 10, 2012
    Excerpt: As detailed in my second post on alternative splicing, there is one human gene that codes for 576 different proteins, and there is one fruit fly gene that codes for 38,016 different proteins!
    While the fact that a single gene can code for so many proteins is truly astounding, we didn’t really know how prevalent alternative splicing is. Are there only a few genes that participate in it, or do most genes engage in it? The ENCODE data presented in reference 2 indicates that at least 75% of all genes participate in alternative splicing. They also indicate that the number of different proteins each gene makes varies significantly, with most genes producing somewhere between 2 and 25.
    Based on these results, it seems clear that the RNA transcripts are the real carriers of genetic information. This is why some members of the ENCODE team are arguing that an RNA transcript, not a gene, should be considered the fundamental unit of inheritance.

    Not only is there ‘unexpected’ widespread alternative splicing of genes, but, as the Sanford paper alluded to, there are also multiple overlapping codes in the same sequence:

    Second, third, fourth… genetic codes – One spectacular case of code crowding – Edward N. Trifonov – video

    In the preceding video, Trifonov elucidates codes that are, simultaneously, in the same sequence, coding for DNA curvature, Chromatin Code, Amphipathic helices, and NF kappaB. In fact, at the 58:00 minute mark he states, “Reading only one message, one gets three more, practically GRATIS!”. And please note that this was just an introductory lecture in which Trifinov just covered the very basics and left many of the other codes out of the lecture. Codes which code for completely different, yet still biologically important, functions. In fact, at the 7:55 mark of the video, there are 13 codes that are listed on a powerpoint, although the writing was too small for me to read.

    Concluding powerpoint of the lecture (at the 1 hour mark):

    “Not only are there many different codes in the sequences, but they overlap, so that the same letters in a sequence may take part simultaneously in several different messages.”
    Edward N. Trifonov – 2010

    Supplemental notes:

    Design In DNA – Alternative Splicing, Duons, and Dual coding genes – video (starting at 5:05 minute mark)

    Multidimensional Genome – Dr. Robert Carter – video (Notes in video description)

  2. 2
    Axel says:

    Great idea! It would cover any number of exclamations of delight at evolution’s cornucopia of ‘chocolate-box’ surprises, wouldn’t it?

  3. 3
    Dionisio says:

    What say we copyright the expression “than previously thought”?

    We won’t charge anybody to use it, but after it’s been used five times in a publication like The Scientist , we’ll insist that they write an editorial explaining why they haven’t come to expect this by now.

    I like the idea.
    However, perhaps the frequency of the expression “…than previously thought” in some scientific publications is more related to wishful thinking than to not noticing the overwhelming evidences.
    Therefore, if we insist that they write an editorial explaining why they haven’t come to expect this by now, most probably they will respond that we are just a bunch of ignorant IDiots who don’t understand evolution. 😉

  4. 4
    Dionisio says:

    “The main point is that a vast new area of biology, previously missed, has been uncovered,”

    We ain’t seen nothing yet. The party has just started, the fun part is still ahead.
    That’s why we should look forward, with much anticipation, to reading future research reports, which will keep shedding light on the mind-boggling choreographies and orchestrations seen in the biological systems. 🙂

    BTW, can’t wait to see gpuccio’s next OP in this blog, though I like that he takes time to write it well. I’m sure that new thread will provoke very good follow-up comments. 🙂

  5. 5
    Dionisio says:

    “This is an incredible study that fundamentally changes how we look at the protein-synthesis machinery,”

    No comments.

  6. 6
    Dionisio says:

    “The unexpected and potentially vast expanded functional networks that emerge from this study have the potential to influence virtually any aspect of cell growth.”

    no comments

  7. 7
    Dionisio says:

    “This is an interesting finding and fits into the existing paradigm that, in many cases, a single gene is processed in various ways [in the cell] to have alternative functions,”

    No comments

  8. 8
    Dionisio says:

    “… [these proteins] will play some biological roles,”

    “[…] interesting biological functions will come out of future studies on these variants.”

  9. 9

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