Evolutionary divergence of the vertebrate TNFAIP8 gene family: Applying the spotted gar orthology bridge to understand ohnolog loss in teleosts

Abstract

Comparative functional genomic studies require the proper identification of gene orthologs to properly exploit animal biomedical research models. To identify gene orthologs, comprehensive, conserved gene synteny analyses are necessary to unwind gene histories that are convoluted by two rounds of early vertebrate genome duplication, and in the case of the teleosts, a third round, the teleost genome duplication (TGD). Recently, the genome of the spotted gar, a holostean outgroup to the teleosts that did not undergo this third genome duplication, was sequenced and applied as an orthology bridge to facilitate the identification of teleost orthologs to human genes and to enhance the power of teleosts as biomedical models. In this study, we apply the spotted gar orthology bridge to help describe the gene history of the vertebrate TNFAIP8 family. Members of the TNFAIP8 gene family have been linked to regulation of immune function and homeostasis and the development of multiple cancer types. Through a conserved gene synteny analysis, we identified zebrafish orthologs to human TNFAIP8L1 and TNFAIP8L3 genes and two co-orthologs to human TNFAIP8L2, but failed to identify an ortholog to human TNFAIP8. Through the application of the orthology bridge, we determined that teleost orthologs to human TNFAIP8 genes were likely lost in a genome inversion event after their divergence from their common ancestor with spotted gar. These findings demonstrate the value of this enhanced approach to gene history analysis and support the development of teleost models to study complex questions related to an array of biomedical issues, including immunity and cancer.

Oncogenic Role of Tumor Necrosis Factor α-Induced Protein 8 (TNFAIP8)

“…TIPE1 shares 55.9%, TIPE2 shares 52.7%, and TIPE3 isoform 2 shares 56.4% amino acid identity with TNFAIP8 isoform 2. In addition, TIPE1 shares 78.7%, TIPE2 shares 75.5%, and TIPE3 isoform 2 shares 80.9% amino acid sequence similarity with TNFAIP8 isoform 2 (Figure 1A, , accessed on: 10 October 2018) [23]. Interestingly, mouse TNFAIP8 shares 89.4% amino acid sequence identity and 94.4% amino acid sequence similarity with human TNFAIP8 (Figure 1A).…”

Nutrigenomic marker discovery by de novo transcriptomic sequencing during early development of the tropical gar ( Atractosteus tropicus )

“…Previously, some studies highlighted the importance of the Lepisosteidae family as a basal group that allows comparisons between teleostean fish and tetrapods (Amores et al, 2011; Braasch et al, 2014; Eames et al, 2012; Katsu et al, 2008; Pasquier et al, 2016). The genome of Lepisosteus oculatus is the only one completely annotated for this family (Braasch et al, 2016), and this has allowed more complex studies on the functionality of genes in this group (Cal et al, 2017; Martin & Holland, 2017; Sullivan et al, 2017; Wcisel et al,. 2017).…”

Tumor Necrosis Factor-α Induced Protein 8: Pathophysiology, Clinical Significance, and Regulatory Mechanism

“…It has also been named as NDED, Oxi-α, GG2-1, MDC3.13 in the early few years. TNFAIP8 gene is highly conservative among various species 16 , 17 , and human TNFAIP8 gene is located at 5 chromosome q23 region 18 , 19 . The open reading frame of TNFAIP8 gene is a specific sequence in its amino-terminal which is extremely homologous to DED II domain in Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (FLIP) 20 .…”