Genome complexity: DNA tiny part of the controls (Introduction)

by David Turell , Thursday, January 03, 2019, 19:35 (2152 days ago) @ David Turell

DNA codes for protein but we still do not know what runs life:

http://nautil.us/issue/68/context/its-the-end-of-the-gene-as-we-know-it

"The existence of a powerful code-script seemed to be confirmed with the discovery of the structure of DNA by Watson and Crick in 1953. They revealed how the sequences of components (called nucleotides) in DNA could serve as a template—a code—for a protein, much as a typewriter sequences letters to form words. So the accepted “central dogma” could be conceived as the one-way flow of information from the code in the gene:

"DNA template → proteins → developing characteristics; as if production of the words alone is tantamount to writing the whole “book” of a complex being.

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"Scientists now understand that the information in the DNA code can only serve as a template for a protein. It cannot possibly serve as instructions for the more complex task of putting the proteins together into a fully functioning being, no more than the characters on a typewriter can produce a story.

"This can seem confusing to those of us indoctrinated in the idea that there must be a set of genetic instructions prior to development: If not in the DNA code, then where? By the 1980s, research findings started to turn that notion on its head.

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"Accordingly, even single cells change their metabolic pathways, and the way they use their genes to suit those patterns. That is, they “learn,” and create instructions on the hoof. Genes are used as templates for making vital resources, of course. But directions and outcomes of the system are not controlled by genes. Like colonies of ants or bees, there are deeper dynamical laws at work in the development of forms and variations.

"Some have likened the process to an orchestra without a conductor. Physiologist Denis Noble has described it as Dancing to the Tune of Life (the title of his recent book). It is most stunningly displayed in early development. Within hours, the fertilized egg becomes a ball of identical cells—all with the same genome, of course. But the cells are already talking to each other with storms of chemical signals. Through the statistical patterns within the storms, instructions are, again, created de novo. The cells, all with the same genes, multiply into hundreds of starkly different types, moving in a glorious ballet to find just the right places at the right times. That could not have been specified in the fixed linear strings of DNA.

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"It is such discoveries that are turning our ideas of genetic causation inside out. We have traditionally thought of cell contents as servants to the DNA instructions. But, as the British biologist Denis Noble insists, “The modern synthesis has got causality in biology wrong … DNA on its own does absolutely nothing until activated by the rest of the system … DNA is not a cause in an active sense. I think it is better described as a passive data base which is used by the organism to enable it to make the proteins that it requires.”

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"But more evolved functions—and associated diseases—depend upon the vast regulatory networks mentioned above, and thousands of genes. Far from acting as single-minded executives, genes are typically flanked, on the DNA sequence, by a dozen or more “regulatory” sequences used by wider cell signals and their dynamics to control genetic transcription.

"This explains why humans seem to have only a few more genes than flies or mice (around 20,000), while a carrot has 45,000! There is no correlation between the complexity of living things and the number of genes they have. But there is a correlation with the evolving complexity of regulatory networks. Counting genes to understand the whole is like judging a body of literature by counting letters. It can’t be done.

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"More startling has been the realization that less than 5 percent of the genome is used to make proteins at all. Most produce a vast range of different factors (RNAs) regulating, through the network, how the other genes are used.

"Increasingly, we are finding that, in complex evolved traits—like human minds—there is little prediction from DNA variation through development to individual differences. The genes are crucial, of course, but nearly all genetic variations are dealt with in the way you can vary your journey from A to B: by constructing alternative routes. “Multiple alternative pathways … are the rule rather than the exception,” reported a paper in the journal BioSystems in 2007.

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" we can now understand why the same genetic resources can be used in many different ways in different organs and tissues. Genes now utilized in the development of our arms and legs, first appeared in organisms that have neither. Genes used in fruit flies for gonad development are now used in the development of human brains. And most genes are used in several different tissues for different purposes at the same time.

"In a paper in Physics of Life Reviews in 2013, James Shapiro describes how cells and organisms are capable of “natural genetic engineering.” That is, they frequently alter their own DNA sequences, rewriting their own genomes throughout life. The startling implication is that the gene as popularly conceived—a blueprint on a strand of DNA, determining development and its variations—does not really exist."

Comment: the whole system of genetic controls is still a giant black box.