We have reached peak gene, and passed it.
Ken Richardson in "It's The End Of The Gene As We Know It"
In scientific, as well as popular descriptions today, genes “act,” “behave,” “direct,” “control,” “design,” “influence,” have “effects,” are “responsible for,” are “selfish,” and so on, as if minds of their own with designs and intentions.
But at the same time, a counter-narrative is building, not from the media but from inside science itself.... 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....
First, laboratory experiments have shown how living forms probably flourished as “molecular soups” long before genes existed. They self-organized, synthesized polymers (like RNA and DNA), adapted, and reproduced through interactions among hundreds of components. That means they followed “instructions” arising from relations between components, according to current conditions, with no overall controller: compositional information, as the geneticist Doron Lancet calls it....
In this perspective, the genes evolved later, as products of prior systems, not as the original designers and controllers of them. More likely as templates for components as and when needed: a kind of facility for “just in time” supply of parts needed on a recurring basis.
We have traditionally thought of cell contents as servants to the DNA instructions. But, as the British biologist Denis Noble insists in an interview with the writer Suzan Mazur, “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.”
PS: the proposed definition of "gene" by Portin and Wilkins:
A gene is a DNA sequence (whose component segments do not necessarily need to be physically contiguous) that specifies one or more sequence-related RNAs/proteins that are both evoked by Genetic Regulatory Networks and participate as elements in Genetic Regulatory Networks, often with indirect effects, or as outputs of Genetic Regulatory Networks, the latter yielding more direct phenotypic effects.Wiki tells us: A genetic regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expressionlevels of mRNA and proteins.
Guest · 307 weeks ago
The fertilized egg that becomes human, mouse, or oak tree comes with a set of such mini programs, implemented in proteins and RNA, but they can't make more of themselves, because their blueprints are in the DNA. Only by using the DNA to make more of these and other cellular components can cells grow, divide, differentiate and form organisms.
So DNA is like a program, only it's a very special program, since it also contains instructions for making more computers, and not only the computers but the whole range of components needed to supply the computer with power and other essentials.
Perhaps the most outrageously nonsensical claim in the article is that genetically identical animals exhibit the full range of variability of the wild types. That is simply and utterly false. On the other hand, they aren't truly identical, because there is many a mutation between egg and fully developed organism. For example, the cells in your brain don't contain exactly the same DNA as the egg from which they originate. They will probably have about 1000 point mutations, or variant SNPs, from that egg and each other that occurred in the process of cell division growth and migration that formed your brain.
Incidentally, SNPs (single nucleotide polymorphisms) are just one of the many ways DNA strands can vary. There are also gene duplications, inversions, copy number variants, and many other variations. So SNPs are just a little of the way genomes can differ.
macgupta 81p · 307 weeks ago
Aha! my take-away analogy was that genes are like the persistent store - say the database - in a computer program. The database provides information needed to construct in-memory data structures and objects, but is not the program, nor the loaders or assemblies - those are in the rest of the cell.
Perhaps the most outrageously nonsensical claim in the article is that genetically identical animals exhibit the full range of variability of the wild types. That is simply and utterly false. On the other hand, they aren't truly identical, because there is many a mutation between egg and fully developed organism. For example, the cells in your brain don't contain exactly the same DNA as the egg from which they originate. They will probably have about 1000 point mutations, or variant SNPs, from that egg and each other that occurred in the process of cell division growth and migration that formed your brain.
The SNPs aren't expressed in proteins or regulating RNA, so that is quite irrelevant. The question is the truth of this: "Conversely, 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." Yes, it seems over the top. But here's the J. Freund paper he referred to: https://pure.mpg.de/rest/items/item_2098536/compo...
macgupta 81p · 307 weeks ago
"This list is far from comprehensive and is meant to illustrate our point that significant phenotypic variation, including crossing a threshold to fatal disease, can emerge from animals that have an identical, cloned genetic background, and frequently-occurring differences in mitochondrial DNA cannot be a universal mechanism for a wide spectrum of phenotypic differences. "
Guest · 307 weeks ago
When a somatic cell is reprogrammed to become a zygote in cloning, the reprogramming consists of essentially of resetting the epigenetic flags to a starting configuration. This resetting process may well be imperfect, resulting in developmental failures in the clone.
Guest · 307 weeks ago
That is not true in general. A SNP is the change in any base pair in the genome. SNPs in genes or regulatory regions are the most interesting ones and the most often tested for. SNPs in genes may be synonymous, nonsynonymous, or frame disrupting. Synonymous changes don't change the coded for amino acid and usually (but not invariably) don't have physiological consequences, nonsynonymous changes change the amino acid and the protein. Frame changing (also called nonsense) SNPs usually abolish the produced protein. Sickle cell anemia is usually produced by a single SNP. So are most other genetic diseases.
Rather, they develop to exhibit the full range of bodily and functional variations found in normal, genetically-variable, groups. Not over the top - categorically false. I've read the cited paper and can find no place where it makes such a claim. What it does find is behavioral plasticity - mouse brains, like human brains, learn from their experiences. Also, at least some learning is associated with post developmental neurogenesis.
Finally, programs are data (at least in the von Neumann paradigm), but not all data consists of programs. Genes are instructions which when implemented result in the production of RNA and (in the case of mRNA) proteins. All those other components of the cell (RNA, proteins, membranes) are coded for, directly or indirectly, by the genes.
macgupta 81p · 307 weeks ago
Guest · 307 weeks ago
Slightly off topic, but FOXP2 is a famous gene, active in the brain and elsewhere. It differs in exactly two SNPs from the version found in other great apes. Another additional SNP in FOXP2 seriously disrupts human language. The protein it produces is purely regulatory - it modifies the amount of expression of other genes. Most of the genes active in the human brain that differ from the versions found in other great apes are regulatory genes. So our brains, which are three or more times larger than those of the other great apes, differ almost entirely in being retuned - like a race car engine. Completely novel proteins are very rare in the human brain.
Guest · 307 weeks ago
You might be interested in the book: "She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity" by Carl Zimmer. It's better at explaining many things than most of the genetics textbooks I have read.
Guest · 307 weeks ago
macgupta 81p · 307 weeks ago
"A gene is a DNA sequence (whose component segments do not necessarily need to be physically contiguous) that specifies one or more sequence-related RNAs/proteins that are both evoked by Genetic Regulatory Networks and participate as elements in Genetic Regulatory Networks, often with indirect effects, or as outputs of Genetic Regulatory Networks, the latter yielding more direct phenotypic effects."
Guest · 307 weeks ago