Genome complexity: what genes do and don't do (Introduction)

by David Turell , Sunday, January 13, 2019, 15:46 (1931 days ago) @ David Turell

A careful article on the limits to what we understand about genes:

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

"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.

"Then came the brilliant technology for sequencing genes (the components or “letters” in the DNA) in the whole genome.

"Now, in low-cost, highly mechanized procedures, the search has become even easier. The DNA components—the letters in the words—that can vary from person to person are called single nucleotide polymorphisms, or SNPs. The genetic search for our human definition boiled down to looking for statistical associations between such variations and differences in IQ, education, disease, or whatever.

" Only a few extremely weak associations between SNPs and observable human characteristics could be found.

"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. (my bold)

***

"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.

***

" as the British biologist Denis Noble insists in an interview with the writer Suzan Mazur,1 “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.” (my bold)

***

"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.

***

"it is now well known that a group of genetically identical individuals, reared in identical environments—as in pure-bred laboratory animals—do not become identical adults. Rather, they develop to exhibit the full range of bodily and functional variations found in normal, genetically-variable, groups. In a report in Science in 2013, Julia Fruend and colleagues observed this effect in differences in developing brain structures.

" 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: We have a long way to go to really understand how the orchestrated layers of the genome works. Note my bolds. Fascinating article in the whole.