Hox genes rap & reptiles

I found this rap video on Hox genes (yes really) on a couple of other blogs over the past week.  Its so good I thought I’d post it here.

And now that you’re all familiar with the basics of Hox genes…   a recent study in Genome Research has found some rather unusual features of this gene family in lizards.  Hox genes play an important role in specifying the anterior-posterior body plan in the developing embryo, and are found in ordered clusters in the genome.  Vertebrates have 4 clusters (A, B, C, and D), with each cluster containing multiple Hox genes.  

This figure shows the 4 Hox clusters in mammals, colour-coded according to where they are expressed in the developing embryo

This figure shows the 4 Hox clusters in mammals, colour-coded according to where they are expressed in the developing embryo

Hox clusters are unusual in that there is very little repetitive DNA  between the genes (repetitive elements being a large fraction of most eukaryotic genomes).  Thus, in most vertebrates Hox genes are located close together, in a tightly ordered sequence.  

Di Poi and colleagues from the University of Geneva analysed the arrangement of Hox clusters in the green anole lizard, the first reptile to have its entire genome sequenced, and found a massive accumuation of repetitive DNA in the Hox region.  This means that, although the general organisation of the genes is the same as in other vertebrates, the genes are much more spread out and the clusters are bigger.

You may be wondering why this extra DNA matters?   Well the important thing to know about Hox genes is that the chromosomal location of any given Hox gene influences both the timing of its expression, and where it is expressed along the developing body axis.  Genes that are anterior in the Hox clusters are expressed early and in the anterior part of the embryo, whereas genes that are posterior in the clusters are expressed later and towards the posterior of the embryo.  In this way, the Hox clusters function as a kind of “clock”, leading to the relatively conserved body plans we see across vertebrates.   Squamates (lizards and snakes) are one of two groups of vertebrates that show an usually large degree of variation in their body plans (teleost fish being the other).  The type of repetitive elements found in the anolis Hox cluster are retrotransposons, which are mobile DNA elements that are particularly associated with alterations in gene expression.   It is possible that the addition of these retrotransposons to the Hox gene clusters in squamates may have modified how the genes are regulated, opening the way for substantial variations in their timing and place of expression, and allowing the evolution of a spectacular variety of morphological variation.   However, the green anole is so far the only lizard where the arrangement of Hox clusters has been investigated, so the significance of these findings won’t be confirmed until this study is extended to other lizards and snakes.

Reference: Nicolas Di-Poï, Juan I. Montoya-Burgos, and Denis Duboule (2009) Atypical relaxation of structural constraints in Hox gene clusters of the green anole lizard. Genome Research doi:10.1101/gr.087932.108 

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