Wednesday, July 23, 2014

On the mythology of natural selection: Part VII. Phenogenetic drift

We are trying in this series of posts (see this week and last, beginning with Part I here) to enumerate a few ways in which organized traits can arise without the usual canonical view of natural selection as the complete, force-like causal process.  We do this to temper what we see as an often unquestioning belief in natural selection.  We do this because such a belief leads to what we think is extreme, and unwarranted, genomic determinism and belief in inborn inherency that leads both to potentially disastrous societal consequences and false hopes in regard to promises for health and well-being.

Also, mistaken reliance on simplistic explanations impedes the effort to understand the truth rather than mythology about the truth--because mythology removes a sense that we must work harder to understand the actual truth.

Today, we wish to note an important aspect of the relationship between genes and traits, even if one were to accept a purely "Newtonian" law- or force-like version of ubiquitous natural selection as the, that is the, cause of traits in organisms.

The point is that even then, and even if genes (broadly defined, without quibbling about what a 'gene' is) worked in a perfectly force-like deterministic causal way, even ignoring all the obvious probabilistic aspects or environmental components, even then, genetic determinism is not the simple story as is often portrayed.

"Survival of the fittest"?  A non-sensical notion too widely adopted
It is blatantly clear to anyone wishing to make even the most casual observation of nature rather than a book of slogans, that 'survival of the fittest' is at the very best a misleading term.  What does 'the' mean? The one and only most-fit individual?  Clearly not!  All those who are fit (here 'fit' refers to success in the evolutionary screen of natural selection)?  Or somewhat fit?  If that, then what does 'fittest' mean?  All those 'equally' best or only the very best survive?  That is an untestable definition.

Darwin should not have adopted this phrase, which he borrowed from Herbert Spencer to clarify, one might say, his term 'natural selection' to make sure that no one would think he (Darwin) was imagining God as nature's selector. The plain and manifest truth is that 'survival' is not exactly the right term so Darwin mis-spoke or spoke metaphorically, because it is both survival and reproduction that are important, and for most species not just survival per se but length or timing of survival, etc.  What Darwin probably meant was 'survival' in the sense of being represented in the next generation.  In any case, semantics aside, in the hurly-burly of real life, evolutionary success is a problematic, quantitative rather than simple qualitative yes-no phenomenon.

It is common if not typical or even necessary that biological traits are produced by the action of many functional elements of an organism's genome, not just one.  Traits themselves usually have at least some variation among individuals within and between species (and during each one's life).  Here we ignore environmental factors, but their variation is of course often an important additional contributor to trait variation. Essentially, life is causally a many-to-many phenomenon.

This fact has profound implications for our understanding of phenogenetic relationships, that is, relationships between genes and the traits to which they contribute.  To show this clearly, in what follows, we will for the sake of argument just assume the force-like universal view of simplistic natural selection.

Divergence of primordial EMP (enamel) gene. Phenogenetic drift. Source: Kawasaki and Weiss, 2003

Phenogenetic drift
With traits that are affected by many different genes (often called 'polygenic' as a short-hand term), many different genotypes can yield essentially the same phenotype.  This is we have called 'phenogenetic equivalence'.  In the Darwinian arena, individuals with the same trait will have similar fitness prospects--they'll be treated similarly by natural selection--even if their trait is due to different genotypes.  That means that the contributing genetic variants are equally 'fit': they proliferate equally well. Different individuals in a population, or individuals from different populations, or individuals from the same population over different time periods, will have the same traits for different genomic reasons. This kind of causation is essentially the definition or essence of polygenic or causally complex traits.

When this occurs, along with the chance elements in life itself, the chance elements in recombination among genes in genomes and between parents and the gametes they provide to each offspring, the relative frequency of the contributing genomic variants will vary over place and time essentially by chance--they will drift as the term has it. This is the case even when selection of the classical kind is at work, even when the selection is strong. This is phenogenetic drift, or chance changes in the relationship between phenotypes and genotypes. (The phenomenon was discussed in the reference below***, and elsewhere in my work, and see Kawasaki on SCPP genes and mineralization, or Wagner on avian digits, e.g.)

With phenogenetic drift there is no reason to expect that a given gene or genetic variant is necessary or sufficient for the trait.  Genetic determinism has a different kind of meaning than the usual 'marginal' (statistically, on-its-own) view of genetic causation.  One could say that the Predictance, the probability of a given phenotype for a given genotype, was very high, but the Detectance, the probability of a given genotype underlying a given phenotype, was low.

But the common reality, based on countless GWAS and other types of genomewide enumeration studies to relate phenotypes to genotypes, is that such prediction is usually small, trivially so for each individual variant and even if all statistically detected genetic variants are taken into account.  Now and then a strong-effect variant at a specific gene is identified, and one might find evidence that fitness--health or actual survival--is predictable from the genotype at that specific gene.  But that is the exception, the Mendelian tease, the first taste of a drug that leads to the hyper-Darwinian addiction.

The Mendelian tease: peas that followed rules; Ernst Benery Erfurt, 1867.

In sum
For rhetorical purposes we have assumed here that the world is a deterministic Darwinian one, but in fact environments are at least as complex as genomes, the interactions among genes are complex, and probabilistic elements are involved all along the way.  We cannot escape a certain amount of probabilism, either because that is the true essence of biological causation, or at least because our measurements are imperfect. Worse, we don't know all the factors to measure, and when it comes to environments they are always changing and in directions we simply cannot predict.  This is particularly true in the case of humans, because our behavior is based on all sorts of unpredictable cultural elements, so that, for example, disease risks are inherently estimated from past exposures, and our future exposures (diet, environmental chemicals, climate, etc. simply cannot be predicted).  All these factors introduce slippage between genotype and phenotype at any given time, and hence over evolutionary time.

Again: the bottom line is that when many genetic factors contribute to a trait's variation, the combination underlying any given individual's trait can be unique to that individual.  It can be problematic to predict the trait from the genotype (as in 'personalized genomic medicine') or to predict the underlying genotype of an individual's phenotype.  Genetic causation is typically not as deterministic as its widespread, if often implicit, image.

Phenogenetic drift is an obvious fact of life, and it raises important questions related to the DNA sequence conservation issue we considered in the context of functional selection earlier in this series. That's because when contributing factors are experiencing phenogenetic drift, specific genes or variants need not be particularly conserved.  So how is it that when phenogenetic drift is part of life and evolution, there is so much evidence at the gene-by-gene sequence level, for purifying selection, for sequence conservation?  Here is a serious subject for study, though it poses no sort of controversy about adaptive evolution except by showing why simplified views of natural selection are inaccurate and at best incomplete.

The so-called Modern Evolutionary Synthesis, formulated in the 1930s and 40s, united paleontology, Darwinian gradualism, and Mendelian inheritance into a single gene-based view of life and its evolution.  It was, essentially and at least implicitly, focused on the effects of variants at single genes, screened by natural selection.  The theory of population genetics was its mathematical basis, and is usually presented for simplicity's sake in textbooks and classes as focused on single 'Mendelian' (two-allele) models, just like green and yellow peas.  But this almost cartoon-like simplification has widely been implicitly or or even explicitly accepted as the reality, even in current medical school curricula (and widely in 'gene-for' research, a topic we often write about). This view in practice often treats individual genes as having inherent deterministic (causal) value, on their own, free of much recognition of context.

Phenogenetic drift, like other not-Darwinian aspects of genotype-phenotype relationships and their evolution, is simply observable, not mystical, perverse, or in any way arcane or secret.  It belongs in the panoply of tools we have to attempt to understand biological causation and its evolution, fleshing out the skeleton of the process that Darwin was able to intuit with the tools available in his time, and as a corrective to the caricature-like simplism that is so widespread today, even in many professional circles and in the public media.  Of course, nobody admits to being simplistic--but pay attention to what they actually say and how they say it, to see whether you think our impressions are accurate nor not.

***Weiss, K, Fullerton, SM  Phenogenetic Drift and the evolution of genotype-phenotype relationships.  Theoretical  Population Biology, 57: 187-195, 2000.

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