Internal gene duplication

For proteins with more than two domains, each potential duplication is listed separately e.g., a minimum of two duplications would be necessary to produce either a three-domain or a four-domain structure. Members of the pairs in the left-hand column both fall within the same structural subcategory and have fairly similar topologies such pairs are perhaps the result of internal gene duplications. Members of pairs in the right-hand column almost all fall into different major categories of tertiary structure (e.g., one all-helical and one antiparallel jS) presumably they could not have been produced by internal gene duplication. 

RND is a large ubiquitous superfamiiy of transporters with representations in all domains of life. Composed typicahy of about 1000 amino-acid residues, they are arranged as 12 transmembrane hehces proteins with two large hydrophilic extra-cytoplasmic loops between hehces 1 and 2 and hehces 7 and 8. It has been postulated that these proteins developed from an internal gene duplication event. The members of the RND family are also secondary active transporters that catalyze the proton-motive-force driven transport of a range of substrates, including hydrophobic drugs, bile salts, fatty acids, heavy metals, and more (22). 

Amino acid sequences can be searchedfor the presence of internal repeats. Such internal repeats can reveal information about the history of an individual protein itself Many proteins apparently have arisen by duplication of a primordial gene followed by its diversification. For example, calmodulin, a ubiquitous calcium sensor in eukaryotes, contains four similar calcium-binding modules that arose by gene duplication (Figure 4.28). 

Figure 39-16 Detection of internal tandem duplications of the FLT3 gene by PCR and capillary gel electrophoresis of PCR products. Capillary electropherograms show clear resolution of PCR products.The x-axis represents the sizes of PCR products and the y-axis shows the fluorescence intensity, which correlates with the abundance of the PCR product.The upper panel shows a wild type of pattern (blue peak).The middle panel shows an additional peak of greater size than the wild-type peak (blue peak on the left).The blue peak on the right represents a FLT3 internal tandem duplication.The lower pane shows the size markers (red peaks) also present in the upper and middle panels. (See Color Plate 5.)...

Mutations of another tyrosine kinase, FLT3, have been described in acute myeloid leukemias. The majority of these mutations are internal tandem duplications (ITDs) within the juxtamembrane domain (JMD) of the gene, and are present in up to 24% of AML cases. ITDs have been identified in all FAB subtypes of AML, most frequently in acute promyelocyticleukemia (AML FAB-M3). Figure 39-16 (Color Plate 5) shows an example of an FLT3 ITD detected by PCR... 

Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 1996 10 1911-18. 

Multicopper oxidases and cytochrome oxidases are the only proteins known to catalyze the four-electron reduction of O2 to H2O. The multicopper oxidases possess a distinctive subdomain structure (706). Laccase, ascorbate oxidase, and Fet3 have three domains while human ceruloplasmin has six. In all the multicopper oxidases there is significant internal homology among the subdomains suggesting they aU arose from a common gene ancestor by gene duplication (707, 706). 

Kramer, E. M., Di Stilio, V. S. and Schluter, P. M. (2003). Complex patterns of gene duplication in the APETALA3 and PISTILLATA lineages of the Ranunculaceae. International Journal of Plant Sciences, 164,1-11. 

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