Jonathan Wells, the author of The Myth of Junk DNA, offers some thoughts on the limitations of what DNA does. Read this before you pay attention to any more DNA fundamentalism:
We have rigorous experimental evidence that DNA does not even code completely for proteins; in most cases the final forms of proteins are not fully specified by DNA sequences.
After transcription, most multi-exon eukaryotic genes undergo alternative splicing, which changes the sequence. [1] We know of one DNA sequence (a “gene” in now-obsolete parlance) in Drosophila from which over 18,000 different proteins are derived, mostly through alternative splicing. [2]
After alternative splicing, some mRNAs undergo editing, in which various subunits are modified or removed and new subunits are added. [3] Because of alternative splicing and RNA editing, the sequences of most mRNAs are different from the original DNA sequence. Instead, their final forms are specified by processes mediated by huge epigenetic complexes (spliceosomes and editosomes) that respond to extracellular cues and operate differently in different developmental stages.
Even after RNAs are translated into proteins, the latter change in ways that cannot be traced back to DNA sequences. First, proteins with the same amino acid sequences can adopt different three-dimensional folding patterns; these are called “metamorphic proteins.” [4] Second, most proteins are glycosylated: That is, complex carbohydrates are chemically bonded to them to generate enormous diversity in protein functions. [5] Since carbohydrate molecules are branched, they carry many more orders of magnitude of information than linear molecules such as DNA and RNA. This has been called the “sugar code,” and although it is highly specified it is largely
independent of DNA sequence information. [6]
So DNA does not completely specify proteins; but even if it did, it would not specify their spatial locations in the cell or embryo. After a protein is transcribed in the nucleus, it must be transported to the proper location in the cell with the help of cytoskeletal arrays and membrane-bound targets that are not themselves specified solely by DNA sequences. The pattern of spatial information in the membrane — called the “membranome” — is known not to be specified by DNA [7] Since spatial localization is essential for proteins to function properly, this adds yet another layer of complexity to the specification of form and function. [8]
Studies using saturation mutagenesis in the embryos of fruit flies, roundworms, zebrafish and mice also provide evidence against the idea that DNA specifies the basic form of an organism. Biologists can mutate (and indeed have mutated) a fruit fly embryo in every possible way, and they have invariably observed only three possible outcomes: a normal fruit fly, a defective fruit fly, or a dead fruit fly.
[1] Kornblihtt AR, Schor IE, Alló M, Dujardin G, Petrillo E, et al. (2013) Alternative splicing: A pivotal step between eukaryotic transcription and translation. Nat Rev Mol Cell Biol 14:153-165. doi:10.1038/nrm3525
[2] Sun W, You X, Gogol-Döring A, He H, Kise Y, et al. (2013) Ultra-deep profiling of alternatively spliced Drosophila Dscam isoforms by circularization-assisted multi-segment sequencing. EMBO J Jun 21, 2013. doi:10.1038/emboj.2013.144
[3] Peng Z, Cheng Y, Tan BC, Kang L, Tian Z, et al. (2012) Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome. Nat Biotechnol 30:253-260. doi:10.1038/nbt.2122
[4] Bryan PN, Orban J (2010) Proteins that switch folds. Curr Opin Struct Biol 20:482-488. doi:10.1016/j.sbi.2010.06.002
[5] Furukawa K, Ohkawa Y, Yamauchi Y, Hamamura K, Ohmi Y, et al. (2012) Fine tuning of cell signals by glycosylation. J Biochem 151:573-578. doi:10.1093/jb/mvs043
[6] Gabius H-J (2000) Biological information transfer beyond the genetic code: The sugar code. Naturwissenschaften 87:108-121. doi:10.1007/s001140050687
[7] Cavalier-Smith T (2004) The membranome and membrane heredity in development and evolution. In: Hirt RP, Horner DS, eds. Organelles, Genomes and Eukaryote Phylogeny. CRC Press (Boca Raton, FL) pp 335-351.
[8] Wells J (2013) The membrane code: A carrier of essential biological information that is not specified by DNA and is inherited apart from it. In: Marks RJ II, Behe MJ, Dembski WA, Gordon BL, Sanford JC, eds. Biological Information: New Perspectives. World Scientific (Singapore) pp 474-488.
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