Of Transcription Factors, Experiential Inheritance, Second-Order Selection Of Proteins, and Saltatory Evolution

Recently, there has been considerable news generated by a paper recently published in Science, Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution, by A.B. Stergachis et al., and an associated perspective commentary, The Hidden Codes That Shape Protein Evolution, by R.J. Weatheritt and M.M. Babu.  In the popular press the reporting has tended to focus on what is described as the ‘double meaning in genetic code’, with, admittedly, some encouragement from A.B. Stergachis.  While the metaphor of a secondary genetic code may indeed be appropriate to deploy, here, much of the extant discussion has, to my mind, failed to bring into focus the most important implications of both this research and the wider context concerning transcription factors of which it is a part.  The truly remarkable implications of this work - if it holds up - concern the role of transcription factors in facilitating the inheritance of response patterns based on parental experience, and in second-order selection among proteins leading to saltatory evolution.

An acquired characteristic per se cannot directly impact an individual’s genome; thus it cannot directly insure its heritability by the next generation.  However, it certainly may affect the overall likelihood that the organism will succeed in passing its genes to the next generation.  If the acquired trait itself increases the organism’s overall fitness and if the readiness with which the trait was acquired is in any way genetically determined and heritable, then - other things being equal - the fact of the organism’s having acquired the characteristic will increase the likelihood that the progeny will acquire the characteristic at least as readily.  This much was evident from the first.  What has only become apparent in the last decade or so is the role of so-called transcription factors and the associated upregulation or downregulation of genes in facilitating the inheritance of propensities for trait-acquisition based upon the acquisition of macroscopic traits.  Simply put, portions of the genome code for proteins - transcription factors - that variously inhibit or disinhibit transcription from other parts of the genome, and these transcription factors in turn may be activated or inactivated by environmental conditions.  The individual experience of an organism can thus result in upregulation or downregulation of certain genes; if this upregulation or downregulation proves conducive to the organism’s survival and reproduction, the genetic proclivity to upregulate or downregulate under like conditions will be inherited by the next generation, based upon the parent’s experience.  

But, beyond facilitation of what I’m sorely tempted to call ‘soft Lamarckianism’, transcription factors appear to allow for an even more important plasticity - namely evolution stemming from selection pressures operating on a population comprised of different sections of the same genome.  It appears that a given genome exhibits significant redundancy with respect to a number of different protein types:  that is, different sections of the genome code for essentially the same protein.  Critically, this is redundancy with variation:  while the protein types coded for are similar and almost functionally equivalent, the codon sequence, and hence the amino acid sequence, are not quite the same, and there is every reason to believe that the environmental context could be such as to insure that one version of the functional enzyme does a slightly better job than another.  Now consider the role transcription factors might play.  Suppose that there is some feedback mechanism, however indirect, that leads from differential performance to upregulation or downregulation - more specifically, from suboptimal performance of the enzyme variant to downregulation of the section of the genome that coded for it, or from optimal performance to upregulation of the corresponding genome section.  Now we have all the conditions in place for natural selection to occur, operating over a population of genome sections coding for functionally analogous but variant enzymes.  Be it noted this is ‘second-order’ natural selection occurring on top of the first order selection that operates between whole genomes:  when its consequences are viewed at the molecular scale, they will appear as a kind of adaptive learning; while at the macroscopic scale they may manifest as saltatory evolution.

It is also worth observing - as is generally true of cases involving adaptation via second-order selection - that selection pressures favor conservation of such a feedback mechanism, if there are any means by which it can be stumbled upon and conserved.  That is, a mechanism that allows for optimization of enzyme function through selective adaptation constitutes a first-order advantage for the whole genome that possesses it; thus, genomes might be expected to evolve such a feature if a reliably replicable version can be hit on accidentally.  Indeed, it may be the primary reason for the apparent redundancy of protein-encodings in the genome.