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An albino infant wallaby was born to a mother with wild-type body color. PCR and sequencing analyses of TYR (encoding tyrosinase, which is essential for melanin biosynthesis) of this albino wallaby revealed a 7.1-kb-long DNA fragment inserted in the first exon. Since the fragment carried long terminal repeats, we assumed it to be a copy of an endogenous retrovirus, which we named walb. We cloned other walb copies residing in the genomes of this species and of another wallaby species. The copies exhibited length variation, and the longest copy (>8.0 kb) contained open reading frames whose deduced amino acid sequences were well aligned with those of gag, pol, and env of retroviruses. It is unknown through which of the following likely processes the walb copy was inserted into TYR: endogenization (infection of a germline cell by an exogenous virus), reinfection (infection by a virus produced from a previously endogenized provirus), or retrotransposition (intracellular relocation of a provirus). In any case, the insertion into TYR is considered to have been a recent event on an evolutionary timescale because albino mutant alleles generally do not persist for long because of their deleterious effects in wild circumstances. Key words: albinism, marsupial, endogenous retrovirus, retrotransposon, long terminal repeat. Un jeune wallaby albinos est ne d'une mere de type sauvage en ce qui a trait a sa pigmentation corporelle. Des analyses PCR et le sequencage du gene TYR (codant pour la tyrosinase, laquelle est essentielle a la synthese de melanine) de ce wallaby albinos a revele une insertion de 7,1 kb au sein du premier exon. Du fait que l'insertion presentait de longues repetitions terminales, les auteurs ont postule qu'il s'agissait d'une copie d'un retrovirus endogene, lequel a ete nomme walb. Les auteurs ont clone d'autres copies de walb qui etaient presentes au sein des genomes de cette espece et d'autres especes de wallaby. Ces copies affichaient une longueur variable et la plus grande (> 8,0 kb) contenait des cadres de lecture pour des sequences peptidiques qui s'alignaient bien avec celles des genes gag, pol et env des retrovirus. Les auteurs n'ont pu determiner par quel processus la copie de walb s'est inseree au sein du gene TYR : l'endogenisation (infection d'une cellule germinale par un virus exogene), la reinfection (infection par un virus issu d'un provirus ayant subi l'endogenisation auparavant), ou la retrotransposition (relocalisation intracellulaire d'un provirus). Dans tous les cas, l'insertion dans le gene TYR est consideree comme etant recente a l'echelle de l'evolution parce que les mutants albinos n'ont pas tendance a persister au sein de populations sauvages en raison de leur impact deletere. Mots-cles : albinisme, marsupial, retrovirus endogene, retrotransposon, longue repetition terminale., Introduction The lifecycle of retroviruses includes reverse transcription of their RNA genome and incorporation of DNA products into the chromosome of their host cells. If incorporation occurs in a germline [...]

Introduction Albino genetic variants, in which melanin pigment is lost or variably reduced, are found in a broad range of organisms. In mammals, the most extreme albino phenotype is due [...], Tanuki (Nyctereutes procyonoides viverrinus), or Japanese raccoon dog, is a canine native to Japan. Tanuki with complete oculocutaneous albinism are relatively frequent in mountainous areas of mainland Japan. Tyrosinase, which is encoded by the TYR gene, is an enzyme essential for the biosynthesis of melanin pigment. We examined the structure and nucleotide sequence of TYR in an albino tanuki and found that the third exon was removed due to a deletion of approximately 11 kb. In addition, two nonsynonymous nucleotide substitutions were found in the fifth exon. These mutations are possible causes of the albino phenotype; however, the order of occurrence is unclear. Even if the 11-kb deletion was not the first of these mutations, it is considered to cause a total loss of the tyrosinase function because the third exon carries codons for one of the two copper-binding sites of tyrosinase and these sites are essential for the enzyme function. Intriguingly, the deletion was not a simple removal of an 11-kb segment: an internal portion was retained as a segment in the reverse orientation. We propose possible formation processes for this mutation that involve multiple DNA scission events, or an inversion followed by a deletion. Keywords: canidae, tyrosinase, melanin, inversion, mutation. Le tanuki (Nyctereutes procyonoides viverrinus), ou chien viverrin japonais, est un canin indigene du Japon. Des tanukis presentant un albinisme oculo-cutane complet sont relativement frequents dans les regions montagneuses du Japon continental. La tyrosinase, laquelle est codee par le gene TYR, est une enzyme essentielle pour la synthese de la melanine. Les auteurs ont examine la structure et la sequence nucleotidique du gene TYR chez un tanuki albinos et ont observe que le troisieme exon etait absent en raison d'une deletion d'environ 11 kb. De plus, deux substitutions non-synonymes ont ete trouvees dans le cinquieme exon. Ces mutations sont possiblement la cause de l'albinisme; cependant, l'ordre d'apparition de ces mutations n'est pas connu. Meme si la deletion de 11 kb n'etait pas la premiere a survenir, on peut considerer qu'elle cause une perte totale de la fonction du gene car le troisieme exon contient des codons codant pour l'un des deux sites de liaison au cuivre, des sites qui sont essentiels a la fonction enzymatique. Chose intrigante, la deletion n'est pas le produit de la simple perte d'un segment de 11 kb car une portion interne a ete retenue et se presente en orientation inverse. Les auteurs proposent un possible processus de formation de cette mutation qui implique plusieurs evenements de bris de l'ADN, ou encore une inversion suivie d'une deletion. [Traduit par la Redaction] Mots-cles : canides, tyrosinase, melanine, inversion, mutation.

Simple Summary: A transcriptome landscape of therian mammals is known, but it remains unclear how transcriptomic patterns have evolved in a marsupial- or eutherian-specific way. It is important to understand marsupial- or eutherian-specific transcriptomic patterns since their fitness and sex differentiation are different. This study examines therian testis transcriptomes to elucidate marsupial and eutherian uniqueness in male differentiation. Using the massive transcriptomic data, we show the evolutionary tempo and mode of testis-expressed genes in Theria and identify candidate genes involved in the specificity of marsupial or eutherian testes. Gene expression patterns differ in different tissues, and the expression pattern of genes in the mammalian testis is known to be extremely variable in different species. To clarify how the testis transcriptomic pattern has evolved in particular species, we examined the evolution of the adult testis transcriptome in Theria using 10 species: two marsupials (opossum and Tasmanian devil), six eutherian (placental) mammals (human, chimpanzee, bonobo, gorilla, rhesus macaque, and mouse), and two outgroup species (platypus and chicken). We show that 22 testis-expressed genes are marsupial-specific, suggesting their acquisition in the stem lineage of marsupials after the divergence from eutherians. Despite the time length of the eutherian stem lineage being similar to that of the marsupial lineage, acquisition of testis-expressed genes was not found in the stem lineage of eutherians; rather, their expression patterns differed by species, suggesting rapid gene evolution in the eutherian ancestors. Fifteen testis-expressed genes are therian-specific, and for three of these genes, the evolutionary tempo is markedly faster in eutherians than in marsupials. Our phylogenetic analysis of Rho GTPase-activating protein 28 (ARHGAP28) suggests the adaptive evolution of this gene in the eutherians, probably together with the expression pattern differentiation. [ABSTRACT FROM AUTHOR]

Embryogenesis in placental mammals is sustained by exquisite interplay between the embryo proper and placenta. UTF1 is a developmentally regulated gene expressed in both cell lineages. Here, we analyzed the consequence of loss of the UTF1 gene during mouse development. We found that homozygous UTF1 mutant newborn mice were significantly smaller than wild-type or heterozygous mutant mice, suggesting that placental insufficiency caused by the loss of UTF1 expression in extra-embryonic ectodermal cells at least in part contributed to this phenotype. We also found that the effects of loss of UTF1 expression in embryonic stem cells on their pluripotency were very subtle. Genome structure and sequence comparisons revealed that the UTF1 gene exists only in placental mammals. Our analyses of a family of genes with homology to UTF1 revealed a possible mechanism by which placental mammals have evolved the UTF1 genes. [ABSTRACT FROM AUTHOR]

The East Asian region, including China, Japan and Korea, accounts for half of gastric cancer deaths. However, different areas have contrasting gastric cancer incidences and the population structure of Helicobacter pylori in this ethnically diverse region is yet unknown. We aimed to investigate genomic differences in H. pylori between these areas to identify sequence polymorphisms associated with increased cancer risk. We analysed 381  H . pylori genomes collected from different areas of the three countries using phylogenetic and population genetic tools to characterize population differentiation. The functional consequences of SNPs with a highest fixation index (Fst) between subpopulations were examined by mapping amino acid changes on 3D protein structure, solved or modelled. Overall, 329/381 genomes belonged to the previously identified hspEAsia population indicating that import of bacteria from other regions of the world has been uncommon. Seven subregional clusters were found within hspEAsia, related to subpopulations with various ethnicities, geographies and gastric cancer risks. Subpopulation-specific amino acid changes were found in multidrug exporters ( hefC ), transporters ( frpB-4 ), outer membrane proteins ( hopI ) and several genes involved in host interaction, such as a catalase site, involved in H 2 O 2 entrance, and a flagellin site mimicking host glycosylation. Several of the top hits, including frpB-4 , hefC , alpB / hopB and hofC, have been found to be differentiated within the Americas in previous studies, indicating that a handful of genes may be key to local geographic adaptation. H. pylori within East Asia are not homogeneous but have become differentiated geographically at multiple loci that might have facilitated adaptation to local conditions and hosts. This has important implications for further evaluation of these changes in relation to the varying gastric cancer incidence between geographical areas in this region.

Adrenal 4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) (Nr5a1) is a nuclear receptor essential for reproductive tissue development and endocrine regulation. This factor is expressed in steroidogenic tissues (e.g. adrenal glands and gonads), and expression of this factor is tightly regulated in a tissue and cell type-specific manner. Our previous studies have identified tissue and cell type-specific enhancers in the introns of the Ad4BP/SF-1 gene in fetal adrenal glands, ventromedial hypothalamus, and pituitary gonadotrope. Characterization of the enhancers had provided new insights into tissue and cell development. However, these studies have failed to identify any gonad-specific enhancer. Here, we identified a fetal Leydig cell-specific enhancer in the upstream region of the mouse Ad4BP/SF-1 gene using transgenic mouse assays. Alignment of the upstream regions among vertebrate animal species demonstrated that the enhancer consisted of three conserved regions, whereby the most highly conserved region contained an Ad4BP/SF-1 binding sequence and an E-box. Mutation of each sequence abolished the enhancer activity and led to a loss of reporter gene expression. These results suggested that Ad4BP/SF-1 gene expression in the fetal Leydig cell is regulated by a yet unidentified E-box binding protein(s) and by an autoregulatory loop formed by Ad4BP/SF-1. Although fetal Leydig cells have been thought to play crucial roles for masculinization of various fetal tissues through androgen production, other functions have remained elusive. Our identification of a fetal Leydig cell-specific enhancer in the Ad4BP/SF-1 gene would be a powerful tool to address these gaps in the knowledge base.