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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 [...], 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 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]

Recent advances in DNA sequencing technology have enabled the precise decoding of genomes in non-model organisms, providing a basis for unraveling the patterns and mechanisms of sex chromosome evolution. Studies of different species have yielded conflicting results regarding the traditional theory that sex chromosomes evolve from autosomes via the accumulation of deleterious mutations and degeneration of the Y (or W) chromosome. The concept of the 'sex chromosome cycle,' emerging from this context, posits that at any stage of the cycle (i.e. differentiation, degeneration, or loss), sex chromosome turnover can occur while maintaining stable sex determination. Thus, understanding the mechanisms that drive both the persistence and turnover of sex chromosomes at each stage of the cycle is crucial. In this review, we integrate recent findings on the mechanisms underlying maintenance and turnover, with a special focus on several organisms having unique sex chromosomes. Our review suggests that the diversity of sex chromosomes in the maintenance of stable sex determination is underappreciated and emphasizes the need for more research on the sex chromosome cycle. [ABSTRACT FROM AUTHOR]

Sex chromosomes constantly exist in a dynamic state of evolution: rapid turnover and change of heterogametic sex during homomorphic state, and often stepping out to a heteromorphic state followed by chromosomal decaying. However, the forces driving these different trajectories of sex chromosome evolution are still unclear. The Japanese frog Glandirana rugosa is one taxon well suited to the study on these driving forces. The species has two different heteromorphic sex chromosome systems, XX‐XY and ZZ‐ZW, which are separated in different geographic populations. Both XX‐XY and ZZ‐ZW sex chromosomes are represented by chromosome 7 (2n = 26). Phylogenetically, these two systems arose via hybridization between two ancestral lineages of West Japan and East Japan populations, of which sex chromosomes are homomorphic in both sexes and to date have not yet been identified. Identification of the sex chromosomes will give us important insight into the mechanisms of sex chromosome evolution in this species. Here, we used a high‐throughput genomic approach to identify the homomorphic XX‐XY sex chromosomes in both ancestral populations. Sex‐linked DNA markers of West Japan were aligned to chromosome 1, whereas those of East Japan were aligned to chromosome 3. These results reveal that at least two turnovers across three different sex chromosomes 1, 3 and 7 occurred during evolution of this species. This finding raises the possibility that cohabitation of the two different sex chromosomes from ancestral lineages induced turnover to another new one in their hybrids, involving transition of heterogametic sex and evolution from homomorphy to heteromorphy. [ABSTRACT FROM AUTHOR]

With the increasing availability of high quality genomic data, there is opportunity to deeply explore the genealogical relationships of different gene loci between closely related species. In this study, we utilized genomes of Xenopus laevis (XLA, a tetraploid species with (L) and (S) sub-genomes) and X. tropicalis (XTR, a diploid species) to investigate whether synonymous substitution rates among orthologous or homoeologous genes displayed any heterogeneity. From over 1500 orthologous/homoeologous genes collected, we calculated proportion of synonymous substitutions between genomes/sub-genomes (k) and found variation within and between chromosomes. Within most chromosomes, we identified higher k with distance from the centromere, likely attributed to higher substitution rates and recombination in these regions. Using maximum likelihood methods, we identified further evidence supporting rate heterogeneity, and estimated species divergence times and ancestral population sizes. Estimated species divergence times (XLA.L-XLA.S: ~25.5 mya; XLA-XTR: ~33.0 mya) were slightly younger compared to a past study, attributed to consideration of population size in our study. Meanwhile, we found very large estimated population size in the ancestral populations of the two species (NA = 2.55 x 106). Local hybridization and population structure, which have not yet been well elucidated in frogs, may be a contributing factor to these possible large population sizes. [ABSTRACT FROM AUTHOR]

We previously introduced a numerical quantity called the stability (Ps) of an inferred tree and showed that for the tree to be reliable this stability as well as the reliability of the tree, which is usually computed as the bootstrap probability (Pb), must be high. However, if genome duplication occurs in a species, a gene family of the genome also duplicates, and for this reason alone some Ps values can be high in a tree of the duplicated gene families. In addition, the topology of the duplicated gene family can be similar to that of the original gene family if such gene families are identifiable. After genome duplication, however, the gene families are often partially deleted or partially duplicated, and the duplicated gene family may not show the same topology as that of the original family. It is therefore necessary to compute the similarity of the topologies of the duplicated and the original gene families. In this paper, we introduce another quantity called the reproducibility (Pr) for measuring the similarity of the two gene families. To show how to compute the Pr values, we first compute the Pb and Ps values for each of the MHC class II α and β chain gene families, which were apparently generated by genome duplication. We then compute the Pr values for the MHC class II α and β chain gene families. The Pr values for the α and β chain gene families are now low, and this suggests that the diploidization of gene segregation has occurred after the genome duplication. Currently higher animals, defined as animals with complex phenotypic characters, generally have a higher genome size, and this increase in genome size appears to have been caused by genome duplication and diploidization of gene segregation after genome duplication. [ABSTRACT FROM AUTHOR]

Background: Maleness in mammals is genetically determined by the Y chromosome. On the Y chromosome SRY is known as the mammalian male-determining gene. Both placental mammals (Eutheria) and marsupial mammals (Metatheria) have SRY genes. However, only eutherian SRY genes have been empirically examined by functional analyses, and the involvement of marsupial SRY in male gonad development remains speculative. Results: In order to demonstrate that the marsupial SRY gene is similar to the eutherian SRY gene in function, we first examined the sequence differences between marsupial and eutherian SRY genes. Then, using a parsimony method, we identify 7 marsupial-specific ancestral substitutions, 13 eutherian-specific ancestral substitutions, and 4 substitutions that occurred at the stem lineage of therian SRY genes. A literature search and molecular dynamics computational simulations support that the lineage-specific ancestral substitutions might be involved with the functional differentiation between marsupial and eutherian SRY genes. To address the function of the marsupial SRY gene in male determination, we performed luciferase assays on the testis enhancer of Sox9 core (TESCO) using the marsupial SRY. The functional assay shows that marsupial SRY gene can weakly up-regulate the luciferase expression via TESCO. Conclusions: Despite the sequence differences between the marsupial and eutherian SRY genes, our functional assay indicates that the marsupial SRY gene regulates SOX9 as a transcription factor in a similar way to the eutherian SRY gene. Our results suggest that SRY genes obtained the function of male determination in the common ancestor of Theria (placental mammals and marsupials). This suggests that the marsupial SRY gene has a function in male determination, but additional experiments are needed to be conclusive. [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]

Mammalian sex chromosomes originated from a pair of autosomes, and homologous genes on the sex chromosomes (gametologs) differentiated through recombination arrest between the chromosomes. It was hypothesized that this differentiation in eutherians took place in a stepwise fashion and left a footprint on the X chromosome termed "evolutionary strata." The evolutionary stratum hypothesis claims that strata 1 and 2 (which correspond to the first two steps of chromosomal differentiation) were generated in the stem lineage of Theria or before the divergence between eutherians and marsupials. However, this prediction relied solely on the molecular clock hypothesis between pairs of human gametologs, and molecular evolution of marsupial sex chromosomal genes has not yet been investigated. In this study, we analyzed the following 7 pairs of marsupial gametologs, together with their eutherian orthologs that reside in stratum 1 or 2: SOX3/SRY, RBMX/Y, RPS4X/Y, HSFX/Y, XKRX/Y, SMCX/Y (KDM5C/D, JARID1C/D), and UBE1X/Y (UBA1/UBA1Y). Phylogenetic analyses and estimated divergence time of these gametologs reveal that they all differentiated at the same time in the therian ancestor. We have also provided strong evidence for gene conversion that occurred in the 39 region of the eutherian stratum 2 genes (SMCX/Y and UBE1X/Y). The results of the present study show that (1) there is no compelling evidence for the second stratum in the stem lineage of Theria; (2) gene conversion, which may have occurred between SMCX/Y and UBE1X/Y in the eutherian lineage, potentially accounts for their apparently lower degree of overall divergence. [ABSTRACT FROM AUTHOR]

The evolutionary mode of a multi-gene family can change over time, depending on the functional differentiation and local genomic environment of family members. In this study, we demonstrate such a change in the melanoma antigen (MAGE) gene family on the mammalian X chromosome. The MAGE gene family is composed of ten subfamilies that can be categorized into two types. Type I genes are of relatively recent origin, and they encode epitopes for human leukocyte antigen (HLA) in cancer cells. Type II genes are relatively ancient and some of their products are known to be involved in apoptosis or cell proliferation. The evolutionary history of the MAGE gene family can be divided into four phases. In phase I, a single-copy state of an ancestral gene and the evolutionarily conserved mode had lasted until the emergence of eutherian mammals. In phase II, eight subfamily ancestors, with the exception for MAGE-C and MAGE-D subfamilies, were formed via retrotransposition independently. This would coincide with a transposition burst of LINE elements at the eutherian radiation. However, MAGE-C was generated by gene duplication of MAGE-A. Phase III is characterized by extensive gene duplication within each subfamily and in particular the formation of palindromes in the MAGE-A subfamily, which occurred in an ancestor of the Catarrhini. Phase IV is characterized by the decay of a palindrome in most Catarrhini, with the exception of humans. Although the palindrome is truncated by frequent deletions in apes and Old World monkeys, it is retained in humans. Here, we argue that this human-specific retention stems from negative selection acting on MAGE-A genes encoding epitopes of cancer cells, which preserves their ability to bind to highly divergent HLA molecules. These findings are interpreted with consideration of the biological factors shaping recent human MAGE-A 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.

The Japanese wrinkled frog ( Glandirana rugosa ) is unique in having both XX-XY and ZZ-ZW types of sex chromosomes within the species. The genome sequencing and comparative genomics with other frogs should be important to understand mechanisms of turnover of sex chromosomes within one species or during a short period. In this study, we analyzed the newly sequenced genome of G. rugosa using a batch-learning self-organizing map which is unsupervised artificial intelligence for oligonucleotide compositions. To clarify genome characteristics of G. rugosa , we compared its short oligonucleotide compositions in all 1-Mb genomic fragments with those of other six frog species ( Pyxicephalus adspersus , Rhinella marina , Spea multiplicata , Leptobrachium leishanense , Xenopus laevis , and Xenopus tropicalis ). In G. rugosa , we found an Mb-level large size of repeat sequences having a high identity with the W chromosome of the African bullfrog ( P. adspersus ). Our study concluded that G. rugosa has unique genome characteristics with a high CG frequency, and its genome is assumed to heterochromatinize a large size of genome via methylataion of CG., (© 2021 Katsura et al.)

Throughout mammalian evolution, recombination between the two sex chromosomes was suppressed in a stepwise manner. It is thought that the suppression of recombination led to an accumulation of deleterious mutations and frequent genomic rearrangements on the Y chromosome. In this article, we review three evolutionary aspects related to genomic rearrangements and structures, such as inverted repeats (IRs) and palindromes (PDs), on the mammalian sex chromosomes. First, we describe the stepwise manner in which recombination between the X and Y chromosomes was suppressed in placental mammals and discuss a genomic rearrangement that might have led to the formation of present pseudoautosomal boundaries (PAB). Second, we describe ectopic gene conversion between the X and Y chromosomes, and propose possible molecular causes. Third, we focus on the evolutionary mode and timing of PD formation on the X and Y chromosomes. The sequence of the chimpanzee Y chromosome was recently published by two groups. Both groups suggest that rapid evolution of genomic structure occurred on the Y chromosome. Our re-analysis of the sequences confirmed the species-specific mode of human and chimpanzee Y chromosomal evolution. Finally, we present a general outlook regarding the rapid evolution of mammalian sex chromosomes.

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.

We report the results of an extensive investigation of genomic structures in the human genome, with a particular focus on relatively large repeats (>50 kb) in adjacent chromosomal regions. We named such structures "Flowers" because the pattern observed on dot plots resembles a flower. We detected a total of 291 Flowers in the human genome. They were predominantly located in euchromatic regions. Flowers are gene-rich compared to the average gene density of the genome. Genes involved in systems receiving environmental information, such as immunity and detoxification, were overrepresented in Flowers. Within a Flower, the mean number of duplication units was approximately four. The maximum and minimum identities between homologs in a Flower showed different distributions; the maximum identity was often concentrated to 100% identity, while the minimum identity was evenly distributed in the range of 78% to 100%. Using a gene conversion detection test, we found frequent and/or recent gene conversion events within the tested Flowers. Interestingly, many of those converted regions contained protein-coding genes. Computer simulation studies suggest that one role of such frequent gene conversions is the elongation of the life span of gene families in a Flower by the resurrection of pseudogenes.