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I was recently reading about colinearity in the HOX genes that give an organism its high-level body plan (where the order of the HOX genes on the chromosome follow the head-to-tail order of body segments, such that the head gene comes before the thorax gene, comes before the abdomen gene, etc).

I'm really just a layman interested in this stuff (only completed A & P I), but I was under the impression that the location of genes on a chromosome has no bearing on the expression of those genes or phenotype of the organism -- in other words, that genes can be anywhere on any chromosome.

Do we understand how the order of the HOX genes ends up being expressed as the order of the body segments? Do we know why the positioning of these genes matters when the order of other genes don't?

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    $\begingroup$ Have you read Sean Carroll's "Endless forms Most Beautiful" ?I think you will get a complete answer in that book. $\endgroup$
    – biogirl
    Dec 6, 2013 at 9:27
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    $\begingroup$ By the way, the order of the other genes is also important . If it were not so, translocations of bits of chromosomes won't be harmful. Have to confirm this though..... $\endgroup$
    – biogirl
    Dec 6, 2013 at 9:29
  • $\begingroup$ @biogirl maybe you could provide a short synposis of Carroll's book in an answer? $\endgroup$
    – John
    Dec 9, 2013 at 17:45
  • $\begingroup$ To tell you the truth, I have not read it completely. So, it's really difficult for me to answer this. $\endgroup$
    – biogirl
    Dec 9, 2013 at 17:52
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    $\begingroup$ This reply is very late, but for the benefit of biogirl, chromosomal translocations can indeed be harmless, so long as they are gene-dose balanced, and their break-points don't disrupt genes or important regulatory regions. For example, many people live normally with balanced translocations and only find out when they have some trouble conceiving children and receive genetic counselling. Many translocations have occurred in evolutionary time between chimps and humans. The strict collinearity of Hox genes really is something special in animals, I think. $\endgroup$
    – Teige
    Feb 19, 2015 at 17:10

3 Answers 3

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You might be interested in this book

When writing Hox Gene collinearity (or colinearity as it is often misspelled as explain in wiki!) on Google scholar or WebOfKnowledge you will get many results on the subject. It is still today an ongoing debate.

Below are some sentences I pick up from these articles. It is certainly hard to understand as I hardly understood what I wrote! The best for you is to go through this review. It is not easy (at least for me but it is not at all my field) but I think it is the best source of information you can find on the subject.

This and this might also help you to understand the debate on the subject.

There are several types of collinearity:

Spatial collinearity is the sequential 3' to 5' expression of Hox Genes along a body axis. Spatial collinearity can be associated with time dependence where the most 3' is expressed first. This is defined as temporal collinearity.

There are two main models to explain the mechanisms hidden behind this ordering.

  • 1) Collinearity is based on transcriptional regulation and specifically that is limited by the progressive 3' to 5' opening of Hox cluster chromatin and/or mediated by global control regions

  • 2) Collinearity depends on interactions between the Hox genes themselves. These interactions include 'posterior prevalence', a negative interaction among Hox proteins that clearly relates to functional collinearity in Drosophila.

Evolution:

It is suggested that collinearity evolved by repeated tandem duplication of an ancestral ur-Hox Gene

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    $\begingroup$ Great, this is what I was looking for! It says I can award the bounty in 3 hours. You'll receive it as soon as SE lets me. $\endgroup$
    – John
    Dec 12, 2013 at 16:53
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Quoting from some parts of Sean Carroll's book - Endless forms most beautiful, I have tried to provide you with an answer but, remember that this can never suffice for the reading of this great book.

Yes, we do understand how the hox genes' expression is regulated.

From page 126-127

......The establishment of these Hox zones and their subsequent action in sculpting the different forms of repeated parts is the fundamental genetic logic upon which the modular forms of large,biletarian animals is built.

The genetic logic relies on genetic switches at two levels. One set of switches belongs to the Hox genes themselves. these switches activate each Hox gene in different zones that will become different modules of the animal. Another set of switches contain signature sequences that are recognized by Hox proteins and that control how other genes are expressed in different modules.

In both arthropods and vertebrates, the Hox genes are developed in zones along the main body axis. The distinct zones of each Hox gene's expression domain are governed by genetic switches, and seperate switches control Hox gene patterns in different tissues such as the ...... Because of the logic of the genetic switches, the cells that belong to one module express different Hox proteins or combinations of Hox proteins than those in adjacent modules....

Let us take an example of Ubx gene which leads to formation of wings in the 2nd and 3rd thoracic segments of drosophila. This gene is turned off in the first thoracic segment but in the second and third segments, it is turned on. This regulation can be achieved because of the genetic switches which in turn can be switched on or off by activators and repressors. These activators and repressors are unevenly distributed in the embryo and so regulation of switches in different parts of the embryo is possible.

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    $\begingroup$ The question is complex and it is nice that you looked up to your book to find this out. But does it answer to "why the order of the HOX genes correspond to the order of the body parts?" ? $\endgroup$
    – Remi.b
    Dec 12, 2013 at 14:49
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    $\begingroup$ @Remi.b is right. While this is a well-researched answer, it doesn't address specifically the colinearity that I was inquiring about--why the order of these genes on the chromosome matter. $\endgroup$
    – John
    Dec 12, 2013 at 16:00
  • $\begingroup$ @John Well, I just answered the first part of the your question. " Do we understand how the order of the HOX genes ends up being expressed as the order of the body segments? ". $\endgroup$
    – biogirl
    Dec 12, 2013 at 17:39
  • $\begingroup$ @Remi.b answers the second part in an excellent way ! $\endgroup$
    – biogirl
    Dec 12, 2013 at 17:40
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I have suggested that collinearity of Hox genes is a mechanism to maximise physical segregation between active and inactive Hox genes within the Hox gene cluster. This is to minimise interference between Hox genes in these two states. See 'The significance of Hox gene collinearity' in Int. J. Dev. Biol. 2015 Vol 59, pp 159-170. Or download from https://www.researchgate.net/profile/Stephen_Gaunt

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  • $\begingroup$ Thx for your contribution, but your answer does not answer the question "HOW does the order of genes in a DNA string determine the body plan". $\endgroup$
    – lolmaus - Andrey Mikhaylov
    Aug 26, 2018 at 16:15

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