In silico Resurrection of the Ancestral HOX: An Insight on How the Body Plan was Designed

Abstract

The Hox is a group of regulatory genes that produce proteins and direct pattern formation in the developing embryo. The encoded protein, or the homeobox, has a segment called the homeodomain which acts as a transcription factor, binding to other DNA, activating them, and regulating body pattern formation. Despite great changes in the appearance and polarity of organisms, these proteins have been known to be highly conserved throughout evolution. This study employs Bayesian tools to predict the ancestral structure, function, and sequence of the Hox protein by using the basal metazoan phyla as sources for any homologous Hox amino acid sequences that are available from a collaborative online Knowledge-base. Also, these tools have been used to identify which present-day sequences are similar to the generated protein. The reconstructed ancestral sequence has a theoretical pl of 10.01 and a molecular weight of 15.379.4 Da. It has been found that the Scr protein of the Drosophila melanogaster is most comparable to the ancestral sequence. The yeast mating-type protein of Saccharomyces cerevisiae has also been identified as one of the distant relatives of the generated sequence, implying the possible primordial functions of the ancestral Hox. Also, a DNA-binding protein of Arabidopsis thaliana related to auxin expression Ibr root development regulation has been found to be closely related to the ancestral Hox. However distant, the protein's structure, general function, and sequence can be seen to have been relatively conserved through the course of evolution given its relation to evolutionarily novel Hox protein sequences.