A new study from Sweden’s Karolinska Institutet shows that the ‘grammar’ of the human genetic code is more complex than that of even the most intricately constructed spoken languages in the world. The findings, published in the journal Nature, explain why the human genome is so difficult to decipher — and contribute to the further understanding of how genetic differences affect the risk of developing diseases on an individual level.
Under the supervision of Professor Jussi Taipale, researchers at Karolinska Institutet have previously identified most of the DNA words recognised by individual transcription factors. However, much like in a natural human language, the DNA words can be joined to form compound words that are read by multiple transcription factors. However, the mechanism by which such compound words are read has not previously been examined. Therefore, in their recent study in Nature, the Taipale team examines the binding preferences of pairs of transcription factors, and systematically maps the compound DNA words they bind to.
Their analysis reveals that the grammar of the genetic code is much more complex than that of even the most complex human languages. Instead of simply joining two words together by deleting a space, the individual words that are joined together in compound DNA words are altered, leading to a large number of completely new words. More.
And it all just somehow appears, due to Darwinian evolution (natural selection acting on random mutation generating huge levels of information).
Notice, by the way, how it is okay to describe the genome as having a “complex language,” but—as we see in “Claim: Monkeys recognize the basic structure of language,” life forms that have never had a complex language are supposed to provide us with clues about how it works. But monkeys do not go on to develop a language because … ?
So, would studying the complex language of the genome help us understand human language? Or is “language” just a metaphor in this case?
But what does that metaphor imply?
Isn’t there a certain perversity in seeing language as an advanced primate shriekfest that produces nothing but continued shrieking. It;s almost as if not getting anywhere isn’t really a problem, as long as one is not caught asking thoughtful questions.
No matter. Shriek studies will get funded, so they’ll go on. Results don’t much matter in an environment where everyone has agreed not to ask the critical questions.
Can we talk? Language as the business end of consciousness
Human origins: The war of trivial explanations
Here’s the abstract:
Gene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs1, 2, 3. Such sequences are very common in the human genome, and an important determinant of the specificity of gene expression is the cooperative binding of multiple TFs to closely located motifs4, 5, 6. However, interactions between DNA-bound TFs have not been systematically characterized. To identify TF pairs that bind cooperatively to DNA, and to characterize their spacing and orientation preferences, we have performed consecutive affinity-purification systematic evolution of ligands by exponential enrichment (CAP-SELEX) analysis of 9,400 TF–TF–DNA interactions. This analysis revealed 315 TF–TF interactions recognizing 618 heterodimeric motifs, most of which have not been previously described. The observed cooperativity occurred promiscuously between TFs from diverse structural families. Structural analysis of the TF pairs, including a novel crystal structure of MEIS1 and DLX3 bound to their identified recognition site, revealed that the interactions between the TFs were predominantly mediated by DNA. Most TF pair sites identified involved a large overlap between individual TF recognition motifs, and resulted in recognition of composite sites that were markedly different from the individual TF’s motifs. Together, our results indicate that the DNA molecule commonly plays an active role in cooperative interactions that define the gene regulatory lexicon. (paywall) – Arttu Jolma, Yimeng Yin, Kazuhiro R. Nitta, Kashyap Dave, Alexander Popov, Minna Taipale, Martin Enge, Teemu Kivioja, Ekaterina Morgunova, Jussi Taipale. DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature, 2015; DOI: 10.1038/nature15518
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