Moss - What genes cant do - 2003 (522929), страница 14
Текст из файла (страница 14)
The explanatory “game” played by Gene-P is thus not confinedto purely classical methods, which unfortunately has made it all theeasier to conflate this meaning of the “gene” with the one I will refer toas Gene-D.Quite unlike Gene-P, Gene-D is defined by its molecular sequence. AGene-D is a developmental resource (hence the D) which in itself is indeterminate with respect to phenotype. To be a Gene-D is to be a transcriptional unit on a chromosome within which are contained moleculartemplate resources. These templates typically serve in the production ofvarious gene products—directly in the synthesis of RNA and indirectlyin the synthesis of a host of related polypeptides.
To be a gene for NCAM, the so-called neural cell adhesion molecule, for example, is tocontain the specific nucleic acid sequences from which any of 100 potentially different isoforms of the N-CAM protein may ultimately be derived(Zorn & Krieg 1992). Studies have shown that N-CAM molecules are(despite the name) expressed in many tissues, at different developmentalstages, and in many different forms. The phenotypes of which N-CAMmolecules are coconstitutive are thus highly variable, contingent uponthe larger context, and not germane to the status N-CAM as a Gene-D.The expression of an embryonic form (highly sialylated, i.e., furthermodifed by the attachment of long chains of a negatively charged sugar)in the mature organism is associated with neural plasticity in the adultbrain (Walsh & Doherty 1997) but could well have pathological consequences if expressed in other tissues—yet it would not affect the identity of the N-CAM sequence as a Gene-D.
So where a Gene-P is definedstrictly on the basis of its instrumental utility in predicting a phenotypicoutcome and is most often based on the absence of some normalsequence, a Gene-D is a specific developmental resource defined by itsspecific molecular sequence and thereby by its functional template capacity; yet, it is indeterminate with respect to ultimate phenotypic outcomes.A Gene-P allows one to speak predictively about phenotypes, but only(as Johannsen realized) in a limited number of cases and within somecontextually circumscribed range of probabilities. In the absence of, forexample, a full molecular-developmental understanding of the processesresulting in the pathophysiology of cystic fibrosis, it can be prognosti-Genesis of the Gene47cally useful to speak of “the gene for cystic fibrosis.” The normalresource, i.e., the Gene-D located at the cystic fibrosis locus for the greatmajority of individuals who do not have a family history of cystic fibrosis affliction, is not thereby a gene for normal pulmonary function (anymore than the thousands of other genes involved in normal pulmonaryfunction); rather, it is a member of a family of transmembrane ionchannel templates.
As a developmental resource, it is one among verymany that play a direct role in pulmonary development and function (aswell as many other things). To speak of and direct one’s attention tothis gene for a transmembrane ion-conductance regulator protein is tobecome involved in an entirely different kind of explanatory game, i.e.,that of a Gene-D (see table 1.1). There is no preformationist story to behad at this level. To study the biological role and function of this genefor a chloride channel involves locating it within all of the contexts inwhich it is biologically active and attempting to elucidate the causal pathways in which it is an interactant (Kerem & Kerem 1995, Jilling & Kirk1997).
And as with any developmental resource, its status with respectto cause and effect in any given interaction will be contextual and perspectival (i.e., its actions will be viewed as either the cause of somethingor as the result of something else, depending on how a particular inquiryis framed).As a molecular-level developmental resource, Gene-D is ontologicallyon the same plane as any number of other biomolecules—proteins, RNA,oligosaccharides, and so forth—which is to say only that it warrantsno causal privileging before the fact. Gene-P and Gene-D are distinctlydifferent concepts, with distinctly different conditions of satisfactionfor what it means to be a gene.
They play distinctly different explanatory roles. There is nothing that is simultaneously both a Gene-D and aGene-P. That the search for one can lead to the discovery of anotherdoes not change this fact. Finding the Gene-P for cystic fibrosis led tothe identification of a Gene-D for a chloride-ion, conductance-channeltemplate sequence. But the latter is not a gene for an organismic phenotype.
Its explanatory value is not realized (and cannot be realized) inthe form of an “as if” preformationist tool for predicting phenotypes.Rather, the explanatory value of a Gene-D is realized in an analysis ofdevelopmental and physiological interactions in which the direction and48Chapter 1priority of causal determinations are experimentally first revealed (table1.1).The explanatory story in which Genes-D plays a role is not one of preformationism but of epigenesis.
Phenotypes are achieved through thecomplex interactions of many factors, the role of each being contingentupon the larger context to which it also contributes. What is true forNCAM is true for the Gene-D associated with the cystic fibrosis locus,with the breast cancer (BRCA1 and BRCA2) loci, and in fact with allof the genes (Genes-D) being identified at the level of specific molecularsequence by the Human Genome Project. Gene-D, the normal molecular resource at the cystic fibrosis locus, is not a gene for healthy lungsbut a genetic resource that provides template information for a transmembrane, chloride-ion channel, a protein which may be woven intocellular membranes and which plays a functional role in the transportof chloride ions into and out of the cell. Similarly, the normal resourceat the breast cancer locus (BRCA1) is not a gene for healthy breasts buta template for a large and complex protein which is present in many different cell types and tissues and in many different developmental stagesand which also appears to be capable of binding to DNA and influencing cell division in a context-specific way.To study the biology of a Gene-D is to play one kind of explanatorygame, an epigenesic one.
To use a Gene-P, i.e., the absence of a normalgenetic resource, as predictor of a phenotype is to play a different kindof explanatory game, an “as-if” preformationist one. Johannsen was notprivy to Gene-D, and his injunctions do not pertain to them. He predicted that the entirety of the organism would not be decomposed intogenes, and he was right. Genes-D are molecular sequences along thechromosome, not pieces of the phenotype.
Genes-P are spoken of asif they were pieces of the phenotype but, as Johannsen predicted, theypertain only to a limited, and in some sense superficial, set of traits andthen only for practical purposes. Now Gene-D and Gene-P can both beused responsibly within their proper domains. Genetics counselors, forexample, use Gene-P. But just as the word “bank” can be properly usedto mean both the side of a river and a good place to invest money, yetwithout implying that the side of a river is a good place to invest money,so too is the case where the word “gene” should not becomeTable 1.1Gene ConceptExamplesExplanatory ModelOntological StatusGene-PDefined with respect tophenotype but indeterminatewith respect to DNA sequenceGene for breast cancerGene for blue eyesGene for cystic fibrosisPreformationist(instrumental)Conceptual toolNCAM, actinfibronectin, tubulin2000 kinases(28,000 other examples)EpigenesisDevelopmental resource(one kind of molecule amongmany)—Preformationist(constitutive)Virus that invents its own host(“the replicator”)Gene-DDefined with respect to DNAsequence but indeterminate withrespect to phenotypeConflated GeneP/GeneDGenesis of the Gene4950Chapter 1simultaneously invested with the meanings of both Gene-D and Gene-P.Genes are not at once both molecular sequences and pieces of the phenotype, and yet it is precisely this conflationary confusion which hasbuoyed up the notion of the genetic code and a blueprint that regulatesits own execution.While the template relationship that a nucleic acid sequence in DNAhas to a protein (i.e., Gene-D) may be called information, and the predictability (however limited) of a Mendelian unit for the inheritance ofan aberrant (or normal) phenotype may also be called “information,”these can hardly be considered the same kinds of information.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
