Tandem duplication

Beghini, A., Ripamonti, C.B., Cairoli, R., Cazzaniga, G., Colapietro, P., Elice, F., Nadali, G., Grillo, G., Haas, O.A., Biondi, A., et al. (2004) KIT activating mutations incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. 

Park, K.-I. et al.. An intragenic tandem duplication in a transcriptional regulatory gene for anthocyanin biosynthesis confers pale-colored flowers and seeds with fine spots in Ipomoea tricolor. Plant J., 38, 840, 2004. 

Tandem duplication. A duplication in which the repeated regions are immediately adjacent to one another. 

Katinakis, P. Verma, D.P.S. (1985). Nodulin-24 gene of soybean codes for a peptide of the peribacteroid membrane and was generated by tandem duplication of an insertion element. Proceedings of National Academy of Sciences (USA) 82, 4157-61. 

Large-scale deletions, insertions, and tandem duplications of mtDNA are usually not found in blood cells, and the proportions of mtDNA with point mutations in blood cells are generally lower than those in muscle of patients with mitochondrial disease (PI, W5). Thus, the absence of mtDNA mutation in blood samples cannot be used to exclude mitochondrial disease (L7, PI). On the other hand, higher levels of mutant mtDNA are usually found in postmitotic tissues such as cardiac and skeletal muscles and skin tissue of patients. Large-scale deletions or point mutations of mtDNA are generally detectable in muscle biopsies of about 70% of patients with mitochondrial disease (L7, PI). Some of these patients are affected by mutations in nuclear DNA. Other, unknown mutations in mtDNA or nuclear DNA are present in the rest of the patients. 

The following sections explore nature s use of domain swapping to evolve new function. These include the formation of multifunctional proteins, tandem duplication, domain recruitment, and cicular permutation (Fig. 1). The evolution of several enzymes in the purine (Fig. 2) and pyrimidine (Fig. 3) de novo biosynthetic pathways, as well as other enzymes, are discussed as illustrative examples. 

Fig. 1. Schematics of evolutionary mechanisms of domain swapping in nature. Multifunctional proteins arise from the fusion of the genes coding for individual enzymes. Often the individual domains of multifunctional proteins catalyze successive steps in metabolic pathways. In tandem duplication, a gene is duplicated and the 3 end of one copy is fused in-frame to the 5 end of the second copy. In domain recruitment, a functional unit (whole gene or gene fragment) from one gene is either inserted within or fused to an end of a second gene. Circular permuted genes are believed to arise via tandem duplication followed by introduction of new start and stop codons (Ponting el at, 1995).

This begs the question as to why the SYNase domain has evolved by tandem duplication, since both SYN.A and SYN.B seem to be functionally equivalent. However, evidence that the two ATP-dependent reactions occur at different sites in SYNase is very strong (Guy et al., 1996), and it has been subsequently shown that the functional form of SYN.A and SYN.B domains in the absence of the other is a homodimer (Guy et al., 1998). It appears that it is somehow advantageous to have separate, but... 

In contrast to locally separated duplication products, tandem duplication of a gene results in the expression of two or more copies of the gene product within a single polypeptide chain (Fig. 9.1). Such multiplicity has, as reflected by the high frequency of its natural occurrence, clear advantages [7] ... 

Often-cited examples for tandem duplications are pepsin, a member of the aspartate protease family [19], and chymotrypsin, representative of the trypsin-like protease family [20], Structurally, both enzymes consist of two homologous, stacked domains, fi-... 

Circular permutation of a protein results in the relocation of its N- and C-termini within the existing structural framework. Initiated by a tandem duplication of a precursor gene, one mechanistic model proposes an in-frame fusion of the original termini, followed by the generation of a new start codon in the first repeat and a termination site in the second. In support of the model, tandem duplications are observed in prosaposins [29] and DNA methyltransferases [30], both genes for which circular per-mutated variants are also known. 

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