Many people think that biological traits are due to specific genes and that variation in a trait is due to variation in that gene. So it would follow that if a gene variant becomes more frequent, the trait variant it codes for becomes more frequent. We get this idea from Mendel, but it explains only a small fraction of traits; most traits are due to many genes, and this fundamentally changes the specificity of the genotype phenotype connection. To complicate this further, a house may be made of bricks, but the bricks can all be swapped for different bricks, and you've still got the same house. This applies equally to genes and traits.
It may sound mystical to suggest that biology is not "molecular'' at its core the way physics and chemistry are. How can it not be? Life consists of molecules undergoing biochemical reactions that must follow physical laws. We think we understand those laws, but if not, and someone were to discover that they needed revising, life would follow whatever revisions to those laws we came up with. But no one seems to think that currently. Which is not to imply that our understanding of how life works--how those molecular principles apply--is necessarily correct.
In particular, genomes are molecular entities, and the prevailing theory about life is that genomes and their variation drive life and its properties and variation. Under a rather shallow interpretation of Darwinism, genomes bearing specific genotypes that succeed by proliferating themselves because of their functional success, and hence their specific sequence details, are represented with increasing frequency over time.
But suppose it is not a genome per se that is especially conserved by evolution. Suppose the trait, the ephemeral phenotype that is refreshed each generation by new embryos and persistent over time, is really what we need to understand. A phenotype, an individual, is an 'emergent' result of genotypes that is, at present at least, only very imperfectly predictable from its genotype. Since we know that similar phenotypes can be generated by a variety of genotypes, individual genes would then be "only'' the meandering spoor left by the process of evolution by phenotype. Over time a very different set of genotypes might generate a favored phenotype, compared to the genotypes that did so at some time in the past. This phenomenon is called phenogenetic drift.
Perhaps biology has hidden behind the Modern Synthesis, and the idea that all the action is in gene frequencies, for too long. Life is ultimately about phenotypes, the result of interactions by large numbers of genes and other molecular factors, and a better theoretical basis for understanding the dual evolution of phenotype and genotype--the tempo and mode of phenogenetic drift--is needed.
Biology struggled for much of this century to achieve respectability in the pantheon of science, and by mid-century found its "atoms'' in genes. If atoms are 'it', biology had it made! But evolution is less specific and determinative than prevailing, if elegant, molecular and evolutionary theory suggest. Evolution works by phenotypes, whole organisms that reproduce or don't, not genotypes. A phenotype may a vague and ephemeral notion that is a poor excuse for an atom, but it may be the basic "unit" of biology nonetheless, and one we should strive to understand, on its own terms, with the many new methods that now exist.
This is yet another reason to be more circumspect about genomic determinism than many currently are. It is why the determinism of this person's phenotype by his/her genotype may be unique. It's why Darwin's necessary focus on the whole organism rather than just its 'gemmules' was insightful, despite his totally wrong theory of inheritance, and even in an era of rapid and fashionable excitement about the nature of molecules, and specifically genes, as the fundamental physical particles in Nature.
There are probabilistic aspects to gene action, but it may be more important to realize that all genomic functional units are susceptible to variation through mutation, and it is the interaction of countless such units that generates traits, many of whose actual values depend on the environmental factors that interact with DNA's and its products. It is far easier to think of genomes as consisting of beads on a string, than of them as 'mere' contributors to emergent interactions, but the latter is closer to the truth, as countless experiments have by now clearly shown. But, if there is such a thing as a good theory of 'emergence', we don't yet have it, and clearly don't know how to apply it to the eons of ad hoc events, mutational and selectional, that have generated what is here today, not to mention the same sorts of 'slippage' that intervenes between genomes--a person's born DNA sequence, and the person's traits.
Phenogenetic drift, which includes the undeniable equivalence among many different genotypes in terms of the trait values with which they are associated, shows why when we use reductionism to dig below the level of the organism or its traits, to its genome, we pass through the very organizational phenomenon we are trying to understand.
3 comments:
Wonderful, educational post, as always, Ken. A few immediate comments. First, I did actually not know the term “Phenogenetic drift “ until a geneticist pointed it to me last week when we discussed the related (?) phenomenon of “phenocopy” (first proposed, I believe , by Waddington), mentioning that your are a champion of phenogenetic drift. I think it is a useful concept and apt term!
Second, you rightly said: “Perhaps biology has hidden behind the Modern Synthesis, and the idea that all the action is in gene frequencies, for too long. “ This has deep roots: Such attitude is linked, I speculate, to how our mind works: The tendency to connect all observable to a MATERIAL cause that is, that which has a tangible, concrete material embodiment. Hence the many fantasized gods (in the shape of man, animals or combined creatures) and monsters who are in charge for this and that natural phenomenon. Discovering the molecular substrate of the gene (as defined in textbooks) only cemented this desire to reduce the complex observable to tangible quantifiable entities. The precise and careful description and quantification of said material basis can make you look like a serious scientist. In this sense GWAS of mental disorders is nothing but molecular phrenology (which looked like serious science for a while).
Third, you state toward the end: “But, if there is such a thing as a good theory of 'emergence', we don't yet have it” – here I must disagree. The most central and fundamental result of the theory of non-linear dynamical systems is, not deterministic chaos which unfortunately has overshadowed the other results else, but that the very same system with the very same architecture can give rise to multiple, qualitatively and discretely distinct, self-stabilizing system states with memory of themselves even if the event that put the system in that given state has vanished. This is called MULTI-STABILITY. Slight changes of initial conditions can determine which state (phenotype!) will be realized. Conversely, an immense space of different system architectures can produce the very same (or similar) stable behavior (phenotype). This would correspond to your phenogenetic drift. It is precisely because of these two properties, resulting from inescapable mathematical facts, that evolution can work: memory of multiple states and fault tolerance in a system of many interacting parts.
Reply to Sui Huang
Thanks for the thoughtful comments (as always)! My experience with some systems people (not you) is that they essentially talk of systems as if they introduce something profoundly different from standard genomic analysis. Of course, standard hyper beanbag genetics (see an upcoming post or two) is that a system is treated as essentially just another unit, as 'ordinary' reductionists treat a gene or SNP.
Your comment adds interesting things to think about and leads me to ask if you have read Andreas Wagner's papers or book on 'arrival of the fittest'. I think much that we both talk and think about is consistent with his basic points as I understand them, that relates both multiple paths through very complex systems (and phenogenetic drift) as well as the ability without catastrophic jumps to add something new if adaptive circumstances enable it. It reminds me of work Walter Fontana was doing some years ago (maybe still, as I haven't kept up with it) about functional RNAs.
Much to think about....
Thanksgiving's come and gone but I'm very grateful for this post and these comments.
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