Evolution is not always about inventing new proteins but using the same old proteins in different ways to attain a new function and thereby modifying the body plan, leading to the development of new species. Drosophila fushi tarazu serves as a great example for evolution in action and this was demonstrated by Ulrike Lohr lab in 2001, the results of which were published in the current biology journal. This also happens to be one of my all-time favorite works on Hox genes as it displays the gradual change in gene function during the course of evolution with some classic experiments in drosophila. This work from Leslie Pick’s lab was also ahead of time in evo-devo studies as they tested the role of ftz from Tribolium (Tc-Ftz) and Schistocerca Ftz (Sg-Ftz) in the fruit fly Drosophila, which was not a common scenario at beginning of evo-devo era.
ftz functions as a segmentation gene in Drosophila, acts as a pair rule segmentation gene to be precise expressed in even parasegments at blastoderm stage. It is a well known fact that Hox genes are found in clusters but there are some genes in Drosophila cluster which have lost their homeotic property, Bicoid, Zen and ftz are noted examples. ftz is found in between Scr and Antp in the cluster.The Homeodomain in ftz resembles very closely to that of Antp and Scr, but it lacks another conserved motif called hexapeptide (YPWM) which is well characterized for interacting with cofactor extradenticle and thereby important for hox protein function . Interaction with cofactors plays a pivotal role in hox function as hox genes usually don’t act alone while regulating a gene function.
This motif is present in ftz orthologs in Tribolium (beetles) and Schistocerca (grasshopper) suggesting that primitive ftz orthologs are more closely related to ancestral Hox gene than Drosophila ftz (Dm-ftz).
If Dm-ftz is evolved from ancestral hox genes and their segmentation function in Drosophila could be because of change in spatial and temporal expression or due to some changes in protein structure that pushed them towards segmentaion function by losing homeotic activity.
Tribolium and Schistocerca-ftz functions like Antennapedia(Antp) gene of Drosophila:
Some simple but very clean experiments shown that ftz gene from Drosophila has modified its function from homeosis to promoting segmentation during the course of evolution whereas primitve ftz from Tribolium and Schistocerca retained homeotic property with less ability for segmentation.
When they overexpressed ftz from Tribolium and Schistocerca in Drosophila surprisingly they found antenna being transformed to leg somewhat similar to what you observe when antennapedia is over expressed in eye antennal disc. Like antp of Drosophila Tc-ftz transforms larval cuicle to thoracic like (T1 ) and activates teashirt , a target gene of antp. Tc-Ftz represses homothorax (hth),a hallmark of all homeotic genes.Drosophila ftz fails to transform antenna and also cannot activate teashirt expression in head regions.
Tribolium and Schistocerca ftz’s show segmentation potential as well like their Drosophila counterpart,Tribolium mimics Drosophila ftz better than Schistocerca.The segmentation function of Dm-Ftz is strictly dependent on its cofactor, the orphan nuclear hormone receptor Ftz-F1.
Conclusions:
Ftz evolved from ancestral antp gene,as supported by sequence similarity between two genes and phenotypes caused when over expressed.Functional redundancy might have relieved constraints on primodial ftz gene , leading to changes in both regulatory (evident by Dm-ftz expression in striped pattern unlike restricted expression of hometic genes) and protein coding region.Two significant changes in coding sequence of dm-ftz , one being loss of YPWM motif and other is gain of LXXLL motif(used for interaction with ftz-F1 cofactor) facilitated functional evolution of homeotic to segmentaion protein.The loss of homeotic potential of Ftz correlates with the loss of the YPWM motif: Sg-Ftz and Tc-Ftz retain a YPWM motif , whereas Dm-Ftz has lost the YPWM and thus the ability to mediate homeosis.Studying functional evolution of ftz protein gave valuable cues into evo devo mechanisms which promote body plan changes and leading to diversity of species across the animal world.
Reference:
Lahr U, Yussa M, Pick L.
Drosophila fushi tarazu. a gene on the border of homeotic function.
Curr Biol. 2001 Sep 18;11(18):1403-12.