Functional resolution of duplicatedhoxb5genes in teleosts

Abstract

The duplication-degeneration-complementation (DDC) model predicts that subfunctionalization of duplicated genes is a common mechanism for their preservation. The additional Hox complexes of teleost fish constitute a good system in which to test this hypothesis. Zebrafish have two hoxb complexes, with two hoxb5 genes, hoxb5a and hoxb5b, the expression patterns of which suggest subfunctionalization of an ancestral hoxb5 gene. We characterized conserved non-coding elements (CNEs) near the zebrafish hoxb5 genes. One CNE, J3, is only retained in the hoxb5a locus, whereas the others, J1 and J2, are present in both hoxb5 loci. When tested individually, the enhancer activity of individual CNEs, including J3, extensively overlapped and did not support a role in subfunctionalization. By contrast, reporter transgene constructs encompassing multiple CNEs were able to target reporter gene expression to unique domains of hoxb5a and hoxb5b expression. The deletion of J3 from the hoxb5a locus resulted in expression that approached that of hoxb5b, whereas its insertion in the hoxb5b locus increased reporter expression and rendered it more similar to that of hoxb5a. Our results highlight the importance of interactions between CNEs in the execution of complementary subfunctions of duplicated genes.

The Duplicated Deacetylases Sir2 and Hst1 Subfunctionalized by Acquiring Complementary Inactivating Mutations

“…The subfunctionalization of Sir2 and Hst1 through the acquisition of complementary inactivating mutations is a good example of the DDC model of subfunctionalization (13,41). This model was originally discussed in the context of complementary expression patterns, and several examples of this type have been described (10,13,24,32). However, to our knowledge, there are no other well-documented examples of complementary mutations partitioning protein functions.…”

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

“…18,19 Sequences corresponding to the duplicated region were obtained from Ensembl Genome Data Resources from the following contigs: human, NCBI36/hg18, ch17: 956201-1128916; mouse, NCBIM37, ch11: 75 400 000-76 800 000; opossum, BROADO5, ch2: 515 100 000-517 000 000; chicken WASHUC2, ch19: 5 100 000-7 000 000; zebrafish, Zv8, ch15: 24 000 000:25 500 000.…”

Automated identification of conserved synteny after whole-genome duplication

“…The most common fate of genes created by a WGD event, however, is pseudogenization and nonfunctionalization (Li 1980;Watterson 1983). Surviving duplicates can develop new functions (Ohno 1970) or partition or lose their existing functions (Force et al 1999;Lynch and Force 2000;Winkler et al 2003;Postlethwait et al 2004;Jovelin et al 2007;Chain et al 2008;Conant and Wolfe 2008;Jarinova et al 2008). From the time of the duplication event to the present, duplicated genes can alter their expression patterns (Force et al 1999) or their exon structure (Altschmied et al 2002), or their activities (Zhang et al 2002;Zhang 2003), and such changes can alter protein-protein interactions or subsequent developmental or physiological functions.…”