Not building blocks, but networks

– the idea of the organism in genetics and epigenetics

Johannes Wirz

 

The rapid progress of molecular biology cannot escape the fact that the fundamental relationship between phenotype and genotype remains obscure. I postulate that this obscurity will persist because living beings are not realisations of their own genetic program, but – on the contrary – its active interpreters. [...]

 

Pablo Jensen (2001), a science historian and quantum physicist at the Claude-Bernard University in Lyon, masterfully described the capabilities and limitations of a quantum physical view of the macroscopic world:

"A rigorous explanation, with the help of atoms, of the properties of various materials remains problematic and fragmentary. [...] Furthermore, such a connection is peppered with approximations which could never have been made without knowledge of the final results."

If we replace "materials" with "organisms" and "atoms" with "genes", then the above quote also applies to the situation in molecular genetics. The existence of genes is as little challenged as that of elementary particles, but, to this day, the relationship between genetic information and organismic significance largely remains unexplained. [...]

 

The gene in phenotypic and molecular genetics

Fruit fly (Drosophila) with four wings. This phenotype arises from inactivation of the Ubx gene; source: http://www.pbs.org/wgbh/nova/genes/fate-nf.html

[...] In 1995, Edward Lewis was awarded the Nobel Prize for medicine, jointly with Christine Nüsslein-Vollhard and Eric Wieschaus. With ingenious crossing experiments and phenotypic analysis he had studied the genetics of segment identity in Drosophila, and through inactivation of a so-called homeotic gene (Ubx), had produced a fly with four wings (Lewis 1978). Ubx may be regarded as a repressor of wing formation on the third thoracic segment. [...]

It is unclear whether the molecular "body plan" (Bauplan), i.e. the networking of all relevant gene sequences, that ultimately in Drosophila lead to head, thoracic or abdominal segments, will ever be unravelled. Comparable studies with various groups of organisms suggest not, because this gene occurs in mice and humans too, both having totally different body plans from that of Drosophila (Wirz 2000). Whilst it is true that in these higher organisms they are indispensable as necessary conditions for embryonic development, they are not sufficient for the explanation of specific, "causal" developmental processes. Even with animals such as butterflies, which are relatively closely related to two-winged insects, there are some surprises. Although, even in Lepidoptera, Ubx codes for a transcription factor, its organismic significance is diametrically opposite (Levine 2002, Ronshaugen et al. 2002). Wing formation in butterflies is not suppressed, but stimulated! Therefore the bestowal of organismic significance of a gene is dependent on the animal species. A gene sequence is interpreted species-specifically. It is not a sufficient cause but rather a necessary condition for the realisation of development processes. The cause for the phenotypic expression is the organism as a whole.

The fact that, from knowledge of molecular function or base sequence, no phenotypic feature can be derived from a gene, and that the bestowal of significance resides not in the genes but in their carriers, markedly confirm investigations of other gene activities (see for example Moss 2005, who has discussed these findings in detail, Wirz 1997). In modern genetics, the substance of heredity is often described as a text, the human genome as a book of life. Thus a simple example may clarify this matter. What significance do the letters "hat" have? In German, they are a form of a verb. In English they mean a head covering, and in  Norwegian "hate". This code is interpreted according to the language. Any attempt to extract the meaning from the sequence of letters alone has to fail. [...] 

 

 

This text is an excerpt from the article with the same name by Johannes Wirz (Elemente der Naturwissenschaft 88 (2008), pp. 5-21, which may be downloaded here (German).