Identification of a Novel PNMA-MS1 Gene in Marsupials Suggests the LTR Retrotransposon-Derived PNMA Genes Evolved Differently in Marsupials and Eutherians

Abstract

Two major gene families derived from Ty3/Gypsy long terminal repeat (LTR) retrotransposons were recently identified in mammals. The sushi-ichi retrotransposon homologue (SIRH) family comprises 12 genes: 11 in eutherians including Peg10 and Peg11/Rtl1 that have essential roles in the eutherian placenta and 1 that is marsupial specific. Fifteen and 12 genes were reported in the second gene family, para-neoplastic antigen MA (PNMA), in humans and mice, respectively, although their biological functions and evolutionary history remain largely unknown. Here, we identified two novel candidate PNMA genes, PNMA-MS1 and -MS2 in marsupials. Like all eutherian-specific PNMA genes, they exhibit the highest homology to a Gypsy12_DR (DR, Danio rerio) Gag protein. PNMA-MS1 is conserved in both Australian and South American marsupial species, the tammar wallaby and grey short-tailed opossum. However, no PNMA-MS1 orthologue was found in eutherians, monotremes or non-mammalian vertebrates. PNMA-MS1 was expressed in the ovary, mammary gland and brain during development and growth in the tammar, suggesting that PNMA-MS1 may have acquired a marsupial-specific function. However, PNMA-MS2 seems to be a pseudogene. The absence of marsupial orthologues of eutherian PNMA genes suggests that the retrotransposition events of the Gypsy12_DR-related retrotransposons that gave rise to the PNMA family occurred after the divergence of marsupials and eutherians.

PNMA family: Protein interaction network and cell signalling pathways implicated in cancer and apoptosis

“…Regulation of other PNMA family members is currently unknown. Table 2 shows the new locations of 5 PNMA family members reported by Iwasaki et al (2013). From sequence analysis, it was unearthed that hsPNMAs 7, 8 and 16, reported by the earlier group, are indeed, PNMAs.…”

“…PNMA family members are encoded by at least 15 genes localized to human chromosome 14 (PNMA1 and MOAP-1), chromosome 19 (PNMA8A-C, and CCDC8), chromosome 8 (PNMA2), and X chromosome (PNMA3, PNMA5, and PNMA6A, PNMA6B, PNMA6E, PNMA6F, PNMA7A, and PNMA7B, Table 1). In addition, three additional PNMA family members, PNMA6E, 6F, and 8C which are likely to be generated through gene duplication events, were identified after analysis of the human genome databases (GRCh37.p5, GRCh38.p10 [41]). In addition, extensive annotations of the human genome database…”

“…and PNMA7B ( Figure 3A-B). From the sequence analysis, PNMA family members are conserved in quite a number of species, including rat, mouse, monkey, and chimpanzee [4,41]. Further sequence analysis has shown that PNMA family members are conserved in chimpanzee and mouse with the lowest and highest amino acid sequence identity between…”

Sirh7/Ldoc1knockout mice exhibit placental P4 overproduction and delayed parturition

“…Over 30 genes are derived from long terminal repeat (LTR) retrotransposons in two viviparous mammalian groups: the eutherians and marsupials ( Miller et al, 1999 ; Brandt et al, 2005 ; Schuller et al, 2005 ; Youngson et al, 2005 ; Campillos et al, 2006 ; Volff, 2006 ; Ono et al, 2011 ; Kaneko-Ishino and Ishino, 2012 ; Iwasaki et al, 2013 ). Among them, we previously demonstrated that Peg10 and Peg11 ( Rtl1 – Mouse Genome Informatics) of the SIRH family play essential roles in mouse development via the formation and maintenance of the placenta, respectively ( Ono et al, 2006 ; Kagami et al, 2008 ; Sekita et al, 2008 ).…”

LTR retroelements are intrinsic components of transcriptional networks in frogs

“…Circa 80% of these elements within the Silurana genome encode for a chromo domain.The chromo domain is about 40–50 amino acids long. It is contained in various proteins involved in chromatin remodeling and the regulation of gene expression in eukaryotes during development.[56–58]PNMA (Para-neoplastic antigen MA)pfam14893Found so far in about 30% of Cer elements and in about 16% of Gmr elements.This protein domain has so far only been studied in mammals, where it has been associated with neurological disorders.[59, 60]Because of the homology between PNMA proteins and an apoptosis inducing protein (MOAP1), the involvement of PNMA proteins in apoptosis is hypothesized.SCANpfam02023 pfam00096This domain was found in over 50% of Gmr elements only.The SCAN domain family of Zinc finger transcription factors, they are thought to be implicated in regulating genes involved in lipid metabolism, cell survival, and differentiation.[61]Exo/endo phosphatasepfam03372 pfam14529Found in about 12% of Mtanga elements.The exo-/endonuclease phosphatase family of proteins includes magnesium dependent endonucleases and a large number of phosphatases involved in intracellular signaling.[62, 63]Zinc Fingers Zf-H2C2_2 (Zinc-finger double domain)Zf-CCHC (Zinc knuckle)pfam13465About 40% of SnRVs contained a Zinc-finger double domain; about 20% of XEN1 elements contained a Zinc knuckle.Zinc finger (Znf) domains are relatively small but very diverse protein motifs which can target specific molecules. Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organization, epithelial development, cell adhesion, protein folding, chromatin remodeling, and Zinc sensing, to name but a few.[64, 65]pfam00098A Zinc knuckle is a Zinc binding motif of the general structure CX2CX4HX4C where X can be any amino acid.…”