Partitioning of Tissue Expression Accompanies Multiple Duplications of the Na+/K+ ATPase α Subunit Gene

Abstract

Vertebrate genomes contain multiple copies of related genes that arose through gene duplication. In the past it has been proposed that these duplicated genes were retained because of acquisition of novel beneficial functions. A more recent model, the duplication-degeneration-complementation hypothesis (DDC), posits that the functions of a single gene may become separately allocated among the duplicated genes, rendering both duplicates essential. Thus far, empirical evidence for this model has been limited to theengrailed and sox family of developmental regulators, and it has been unclear whether it may also apply to ubiquitously expressed genes with essential functions for cell survival. Here we describe the cloning of three zebrafish α subunits of the Na(+),K(+)-ATPase and a comprehensive evolutionary analysis of this gene family. The predicted amino acid sequences are extremely well conserved among vertebrates. The evolutionary relationships and the map positions of these genes and of other α-like sequences indicate that both tandem and ploidy duplications contributed to the expansion of this gene family in the teleost lineage. The duplications are accompanied by acquisition of clear functional specialization, consistent with the DDC model of genome evolution.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AY028628, AY028629, and AY028630]

Zebrafish: At the Nexus of Functional and Chemical Genomics

“…Many possible outconles exist for duplicated genes. One outcolne is where the function of ancestral genes is split between the two paralogous genes, which has been shown for Na(+), K(+)-ATPase, l-/ox and PllX genes (Force et at., )999; Postlethwait et al, 2000Postlethwait et al, , 2004Serluca et al, 2001). An alternative outcolne is that one copy becolnes inactivated, resulting in a pseudogene.…”

A mutation in the zebrafish Na,K‐ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left‐right asymmetry downstream or in parallel to nodal flow

“…The expression of atp1a1a.1 has previously been reported for mid to late embryogenesis (Rajarao et al, 2001;Serluca et al, 2001). We extended the expression analysis to early embryonic stages.…”

“…This apparent contradiction reflects the fact that zygotic expression of atp1a1a.1 contributes only to a portion of Na,K-ATPase pump activity throughout the organism: First, maternally contributed atp1a1a.1 mRNA will provide an alpha subunit peptide that may be stable well into the second day of development, as membrane proteins often have half lives of 20 hr or more (Mostov et al, 2003). Second, in zebrafish as in other vertebrates, a whole family of genes encodes alpha subunits with different expression patterns (Serluca et al, 2001;Canfield et al, 2002). Due to the ancient genome duplication in zebrafish, there are more family members than in mammalian genomes, and sub-func- tionalization has occurred (Rajarao et al, 2001).…”

“…Canfield et al (2002) found the expression of atp1a1a.1 in the pronephric duct at least until 72 hpf. At 96 hpf, a strong expression was observed in brain, pancreas, and liver (Serluca et al, 2001). During gastrula and somitogenesis stages when leftright asymmetry is established, atp1a1a.1 mRNA is symmetrically distributed in the embryo.…”

“…A gamma subunit has been isolated, which appears not to be essential for pump function, but may modify Na,K-ATPase activity (Blanco and Mercer, 1998). There is a relatively large repertoire of different alpha and beta subunit genes, which have distinct expression profiles during development, along with divers specializations in cellular physiologies (for zebrafish, see Rajarao et al, 2001;Serluca et al, 2001). Our data indicate that one of the functions of the Na,K-ATPase subunit atp1a1a.1 is to contribute to the initiation of left right asymmetry.…”