Hox Genes: Spatial Control of Gene Expression


Many genes that alter embryos code for transcription factors.

These gene sequences are astonishingly conservative through evolution (for example have
homologous sequences in flies and in vertebrates) although they don't necessarily
have the same function. Even small changes are harmful - selective removal of mutants.

Hox (homeotic) genes - found in "all" animals

From the Wikipedia article on Hox genes:

"Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment (e.g. legs, antennae, and wings in fruit flies), and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves."

" Hox genes are thus a subset of the homeobox transcription factor genes. In many animals, the organization of the Hox genes in the chromosome is the same as the order of their expression along the anterior-posterior axis of the developing animal, and are thus said to display colinearity."

Look again at this sentence:
"Hox proteins encode and specify the characteristics of 'position'..."

This statement is widely believed to be true, even as having somehow been proved. But what evidence could either prove or disprove this interpretation?

Can you invent or remember alternative explanations?

What could be meant by "specify the characteristics of 'position"?

Do mutations in such genes result in correct structures that form in incorrect places?

"Hoxbox" - conserved DNA sequences found in all genes whose phenotypes are homeotic, in flies, humans, worms, everything.

Hox genes are located next to each other on chromosomes:
#1, #2, #3, #4, #5, #6, #7, #8, #9, #10, #12, #13,

"Key Question : Why are homeobox genes (very!) similar in all organisms?
Answer: Homeobox genes are crucial for very early embryonic development and are involved in cell differentiation and general body pattern."

Is that quotation a non sequitur?

Please argue pro and/or con

Colinearity of Hox Genes

In some organisms, especially vertebrates, the various Hox genes are situated very close to one another on the chromosome in groups or clusters.

Interestingly, the order of the genes on the chromosome is the same as the
expression of the genes in the developing embryo, with the first gene being
expressed in the anterior end of the developing organism

These genes are transcribed in consistent geometric patterns and time sequences. Those hox genes nearer the lower number end are transcribed sooner, and at locations nearer the animal's head. This very strong correlation between the locations in the embryo where hox genes are first transcribed, relative to the locations of these chromosomes where those genes are located, is called "Colinearity".

"The reason for this colinearity is not yet completely understood ".

This seems to me an extremely tantalizing set of unsolved problems.

What controls locations where each hox gene gets transcribed? How do locations of hox genes on chromosomes control locations in the body where particular hox genes get transcibed? Or does this causal link work in the opposite direction? How does the time sequence control locations in the body where hox genes get transcribed? Or does causation operate the other way round? Are there feedback loops? What is the selective Darwinian advantage to putting these genes next to each other?

What happens when large parts of animals regenerate? Do the regenerating tissues first regenerate which particular hox genes get transcribed in those tissues?

If you relocated hox gene #5 to the location on their chromosome downstream of hox gene #2, what effect would this translocation have on the anatomy of the animal? Would the animal make hox#5 messenger RNA at abnormal locations? Why hasn't anyone solved these questions? They are so obvious! (Although perhaps not so easy? Are these jobs for CRISPR?)