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  • Title: Evolution of developmental genes: molecular microevolution of enhancer sequences at the Ubx locus in Drosophila and its impact on developmental phenotypes.
    Author: Phinchongsakuldit J, MacArthur S, Brookfield JF.
    Journal: Mol Biol Evol; 2004 Feb; 21(2):348-63. PubMed ID: 14660693.
    Abstract:
    Homeotic genes, which function to specify segment identity along the anterior-posterior axis of embryos, are controlled by extensive batteries of enhancer sequences. We have investigated patterns of interspecific and intraspecific molecular variation in three enhancers of the Ultrabithorax (Ubx) locus, which are bx-32.8, pbx32.7, and bxd4.1, from the Drosophila melanogaster species group. These enhancer sequences control Ubx expression by binding to multiple transcription factors encoded by gap, pair-rule, and dorsoventrally expressed genes. Sequence comparisons reveal purifying selection acting on all three enhancers, both in bases binding transcription factors and in bases whose functions are as yet unknown. Neutrality tests largely fail to reject a neutral evolution model. However, using a matrix similarity value to reflect the binding affinity of the protein-binding sites, interspecific and intraspecific variation that may have potential to affect the binding affinity of the sequences homologous to those binding transcription factors in D. melanogaster are discovered, suggesting evolutionary flexibility in the way in which these sequences function in the control of development. As a means of measuring the impact of intraspecific variation on observable phenotypes, we have induced Ubx mutant phenocopies with embryonic ether treatment, and find strong and highly significant variation between D. melanogaster strains in their phenocopy frequencies. This variation shows no significant correlation with the strengths of the mutant phenotypes when the strains are heterozygous with a Ubx null mutation. Estimated phylogenetic trees have been constructed for the three enhancer regions investigated. Neither of the two phenotypic traits investigated shows any significant associations with the phylogeny of any of the three enhancers.
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