3.1 The homeobox genes in vertebrates

The author focus on Hox genes in mammals (rather than homeobox genes in vertebrates), and what he delivers is disappointing in regard with the title.

At the end of the first paragraph he announce: “There seems to be something deeper in the global plan. raising the hope that he will deal with two fundamental aspects of the subject, heredity and evolution, but he fails to do so. The lack of evolutionary perspective and of knowledge of the Hox genes and genetic environment, combined with a poor knowledge of embryology, steadily lead him to misunderstanding, misrepresenting and some quite weird comments and conclusions.

It isn’t even clear in his mind how Hox genes expression is regulated (that requires knowledge of the genetic elemets of the Hox clusters) and why reversion of collinearity isn’t such a big deal to be puzzled about.

The way Hox genes are expressed (or any gene by the way) is not dictated by any rules or concepts, it’s an observation. Genes’ products activity may be as pleiotropic as possible, the same elements participating in more than one physiological function. Elementary stuff.

His description of embryos as unidimensional is at least entertaining at most irritating coming from one who think he have a point of view worth displaying in a physical scientific journal. Development is a 3D+time (plus n dimensions for genes’ expression) process and oversimplifications should be avoided as much as possible.

Homeosis is misrepresented as well, assorted with a false description related with “body plan” when it is about changes of specification of regional identity with nothing to do with any bauplan, body plans being just anatomical descriptions of developments results. Homeotic transformations are as important in vertebrates as in any other animals, the rhetoric trying to minimize their influence in development is ridiculous.

The presumably “universal general bauplan” of vertebrates is heavily biased, comparing fins with limbs, letting aside dorsal, ventral, anal and caudal fins with no equivalent limbs in tetrapods, failing to introduce the neck with its variable number of cervical vertebrae, which contradict his point of view on limbs positioning (see 3.2).

Certainly the worst piece of non-sense is on page 8, column 2, §1:

Moreover, by definition, DNA sequences are linear, and if collinearity between DNA sequences and body form exists as a concept, then nothing can molecularly specify lateral “branchings”, or outgrowths. Lateral outgrowths require a change in growth direction. But such a change is not present as a specific instruction in the genome. This is to say that, while the subsequent genes in the Hox clusters may be correlated to specific forms observed in the stripes (where such or such genes are expressed), there is no interruption of the cluster of genes, by any gene which would serve to instruct a right turn to the growth process. The symmetry breaking which orients growth sideways is a physical, implicit one12 [12 As is, also, the point of intersection of the domains of En, Wg, and Dpp from which insect appendages emanate.], this is to say that it is an instability of the growth process itself, an anisotropy or a tensorial feature.

Let’s start seeing what result one can get with a linear set of values instructing a threshold value and a linear set of data.

1FCA5D9E-E059-4EFD-8D89-672CD4BBCACD.jpg

You can even make it for a 3D anaglyph image

25F6E3A5-D791-48E2-8352-FDA8C0085795.jpg

Or a 3D+time video.

And that’s a poor analogy, just to take ideas out of Fleury’s box.

DNA is not linear by definition, but de facto. And there are some circular DNA genomes/molecules whose circularity is functional. Well, not just some, many, if not most of them actually.

But you don’t expect them to give circular organisms, do you.🙂

Fleury certainly know about GRNs. He certainly read about the combinatorial power they provide, spanning n dimensions, n depending on the number of concerned genes, gene expression control (GEC) elements cis-positioned, interactions of genes’ products between them and with the GEC elements.
Maybe he don’t understand that such networks instruct every single aspect of biological functions, including development, or maybe he don’t want to understand and acknowledge it, as it doesn’t fit with his preconceived point of view.

The symmetry breaking which orients growth sideways is a physical, implicit one“. That’s a very wise observation or a truism. Now, what specifies it, what makes it implicit and differential for different organisms, what specifies the proximo-distal axis? Their genomes is what make the difference between insects and tetrapodes: their genomes specify what symmetry breaking (and where) will take place during their morphogenesis.

It is unfair to the reader to conceal homeobox other than Hox genes, the influence of heredity, biological evolution and importance of genetic information and its regulation of expression, including what concerns innovation in Hox genes cluster regulation of expression, in an effort to make his point of view seem plausible.

One final comment about “why it is so”. I hope nobody expects from a scientific paper to get a response about “why it is so”.

2 Responses

  1. Could we get the password, or is it private ?

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