The functional conservation of proteins in evolutionary alleles and the dominant role of enhancers in evolution.
Drosophila paired- embryos can be rescued to viable adults by the evolutionary alleles prd-Gsb and prd-Pax3, which express the Drosophila Gooseberry and mouse Pax3 proteins under the control of the paired cis-regulatory region. As prd-Gsb uncovers a prd function involved in the proper abdominal segmentation of adults, evolutionary alleles, defined and constructed in this manner, may often be weak and thus serve to discover hitherto unknown functions of a gene. Our findings show that the Gooseberry and Pax3 proteins have conserved most or all functions of the related Drosophila Paired protein although their C-terminal halves appear unrelated in sequence but not in 3-D structure essential for function. It follows that the acquisition of new cis-regulatory regions rather than the divergence of the C-terminal coding regions has been the primary device for the functional diversification of the Drosophila genes paired and gooseberry and the mouse Pax3 gene. The operation of this mechanism in insects as well as vertebrates suggests a major role in evolution.
Xue
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L
Institute for Molecular Biology (II), University of Zürich, Switzerland.
Noll
M
M
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D018628:Gene Dosage; D018398:Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009838:Oligodeoxyribonucleotides; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D011506:Proteins; C489936:Prrx1 protein, mouse; D014157:Transcription Factors; C489935:prd protein, Drosophila; C068686:Pax3 protein, mouse