Duplication and Diversification of the Spermidine/Spermine N1-acetyltransferase 1 Genes in Zebrafish

Abstract

Spermidine/spermine N1-acetyltransferase 1 (Ssat1) is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis. In addition, mammalian Ssat1 is also involved in many physiological and pathological events such as hypoxia, cell migration, and carcinogenesis. Using cross-genomic bioinformatic analysis in 10 deuterostomes, we found that ssat1 only exists in vertebrates. Comparing with mammalian, zebrafish, an evolutionarily distant vertebrate, contains 3 homologous ssat1 genes, named ssat1a, ssat1b, and ssat1c. All zebrafish homologues could be transcribed and produce active enzymes. Despite the long history since their evolutionary diversification, some features of human SSAT1 are conserved and subfunctionalized in the zebrafish family of Ssat1 proteins. The polyamine-dependent protein synthesis was only found in Ssat1b and Ssat1c, not in Ssat1a. Further study indicated that both 5′ and 3′ sequences of ssat1b mediate such kind of translational regulation inside the open reading frame (ORF). The polyamine-dependent protein stabilization was only observed in Ssat1b. The last 70 residues of Ssat1b were crucial for its rapid degradation and polyamine-induced stabilization. It is worth noting that only Ssat1b and Ssat1c, but not the polyamine-insensitive Ssat1a, were able to interact with integrin α9 and Hif-1α. Thus, Ssat1b and Ssat1c might not only be a polyamine metabolic enzyme but also simultaneously respond to polyamine levels and engage in cross-talk with other signaling pathways. Our data revealed some correlations between the sequences and functions of the zebrafish family of Ssat1 proteins, which may provide valuable information for studies of their translational regulatory mechanism, protein stability, and physiological functions.

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

“…In these vertebrates, the detoxification function of NV-AANAT might have been relegated to other enzymes (e.g., spermine/spermidine acetyltransferases) (48,49). From an evolutionary theoretical viewpoint, the history of the AANAT family is an interesting case of neofunctionalization (50); after a gene duplication, one of the copies evolves to assume a new function, and uncharacteristically, the other copy is lost rather than retaining the ancestral function.…”

The minimal gap-junction network among melanophores and xanthophores required for stripe-pattern formation in zebrafish

“…SSAT1 is related to polyamine metabolism, whereas SSAT2 is not (Coleman et al, 2004;Vogel et al, 2006). In zebrafish, three ssat1 homologs, sat1a.1, sat1a.2 and sat1b, exist (Lien et al, 2013). We performed RT-PCR to investigate gene expression of three ssat1 genes in pigment cells and found that only sat1a.2 is expressed in melanophores and xanthophores (Fig.…”

Transcriptional study reveals a potential leptin-dependent gene regulatory network in zebrafish brain

“…We identified 5 genes co-expressed with all the cart genes making a network of co-regulated genes with reduced expression after changes in feeding condition in only wild-type group. Among these genes, ckmt1 , sat1a.2 and arg2 have been shown to be expressed in the brain of zebrafish (Singh et al 2010 ; Drew et al 2012 ; Lien et al 2013 ) and mouse (Yu et al 2001 ; Yang et al 2008 ; Pfefferle et al 2011 ; St-Amand et al 2012 ). Ckmt1 encodes a creatine kinase required for the transfer of high energy phosphate from mitochondria to the cytosolic carrier (creatine), spermidine N1-acetyltransferase 1, sat1a.2 , encodes an enzyme involved in the catabolic pathway of polyamine metabolism, and arginase 2 encoded by arg2 is an enzyme catalysing the hydrolysis of arginine to ornithine and urea.…”