Molecular evolution of interleukin-3 |
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Authors: | Herman Burger Gerard Wagemaker Jack A M Leunissen Lambert C J Dorssers |
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Institution: | (1) Department of Medical Oncology, Dr. Daniel den Hoed Cancer Center/Dijkzigt, University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands;(2) Department of Hematology, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands;(3) CAOS/CAMM Center, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands;(4) Department of Molecular Biology, Dr. Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands;(5) Department of Medical Oncology, University Hospital Rotterdam Dijkzigt, Room 322A, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands |
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Abstract: | Chimpanzee, tamarin, and marmoset interleukin-3 (IL-3) genes were cloned, sequenced, and expressed. Western blot analysis demonstrated that functional genes were isolated. IL-3 sequences were compared with those of mouse, rat, rhesus monkey, gibbon, and man. Multiple alignment of the IL-3 coding regions showed that only a few regions had been conserved during mammalian evolution, which are likely associated with functional domains of the IL-3 protein. Substitution rates for the various lineages were calculated and the numbers of synonymous and nonsynonymous substitutions were estimated separately. Distance matrices of the IL-3 coding regions were used to construct phylogenetic trees which revealed large differences in IL-3 evolution rate as well as a more rapid substitution rate for rodents and a rate slowdown during hominoid evolution. Extremes were rhesus monkey IL-3, which accumulated few synonymous substitutions, and gibbon IL-3, which had almost exclusively synonymous substitutions. In rhesus monkey IL-3, nonsynonymous substitutions outnumbered synonymous substitutions, which could not be readily explained by a random process of substitutions. We assume that during evolution of IL-3, the majority of the amino acid replacements and the impaired interspecies functional cross-reactivity originate from selection mechanisms with the most likely selective force being the structure of the heterodimeric IL-3 cell-surface receptor. Insight into IL-3 architecture and structural analysis of the IL-3 receptor are needed to analyze the unusually fast evolution of IL-3 in more detail. |
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Keywords: | Interleukin-3 Hemopoietic growth factors Molecular evolution (Non)synonymous substitutions Multiple alignment Phylogenetic tree Adaptive evolution |
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