Publications (17)91.94 Total impact
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Article: Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.
Genome biology 12/2011; 12(12):414. · 6.63 Impact Factor -
Article: Evolutionary history of novel genes on the tammar wallaby Y chromosome: Implications for sex chromosome evolution.
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ABSTRACT: We report here the isolation and sequencing of 10 Y-specific tammar wallaby (Macropus eugenii) BAC clones, revealing five hitherto undescribed tammar wallaby Y genes (in addition to the five genes already described) and several pseudogenes. Some genes on the wallaby Y display testis-specific expression, but most have low widespread expression. All have partners on the tammar X, along with homologs on the human X. Nonsynonymous and synonymous substitution ratios for nine of the tammar XY gene pairs indicate that they are each under purifying selection. All 10 were also identified as being on the Y in Tasmanian devil (Sarcophilus harrisii; a distantly related Australian marsupial); however, seven have been lost from the human Y. Maximum likelihood phylogenetic analyses of the wallaby YX genes, with respective homologs from other vertebrate representatives, revealed that three marsupial Y genes (HCFC1X/Y, MECP2X/Y, and HUWE1X/Y) were members of the ancestral therian pseudoautosomal region (PAR) at the time of the marsupial/eutherian split; three XY pairs (SOX3/SRY, RBMX/Y, and ATRX/Y) were isolated from each other before the marsupial/eutherian split, and the remaining three (RPL10X/Y, PHF6X/Y, and UBA1/UBE1Y) have a more complex evolutionary history. Thus, the small marsupial Y chromosome is surprisingly rich in ancient genes that are retained in at least Australian marsupials and evolved from testis-brain expressed genes on the X.Genome Research 11/2011; 22(3):498-507. · 13.61 Impact Factor -
Article: A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation.
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ABSTRACT: Sex chromosome dosage compensation in both eutherian and marsupial mammals is achieved by X chromosome inactivation (XCI)--transcriptional repression that silences one of the two X chromosomes in the somatic cells of females. We recently used RNA fluorescent in situ hybridization (FISH) to show, in individual nuclei, that marsupial X inactivation (in the absence of XIST) occurs on a gene-by-gene basis, and that escape from inactivation is stochastic and independent of gene location. In the absence of similar data from fibroblast cell lines of eutherian representatives, a meaningful comparison is lacking. We therefore used RNA-FISH to examine XCI in fibroblast cell lines obtained from three distantly related eutherian model species: African savannah elephant (Loxodonta africana), mouse (Mus musculus) and human (Homo sapiens). We show that, unlike the orthologous marsupial X, inactivation of the X conserved region (XCR) in eutherians generally is complete. Two-colour RNA-FISH on female human, mouse and elephant interphase nuclei showed that XCR loci have monoallelic expression in almost all nuclei. However, we found that many loci located in the evolutionarily distinct recently added region (XAR) displayed reproducible locus-specific frequencies of nuclei with either one or two active X alleles. We propose that marsupial XCI retains features of an ancient incomplete silencing mechanism that was augmented by the evolution of the XIST gene that progressively stabilized the eutherian XCR. In contrast, the recently added region of the eutherian X displays an incomplete inactivation profile similar to that observed on the evolutionarily distinct marsupial X and the independently evolved monotreme X chromosomes.Chromosoma 09/2011; 121(1):71-8. · 3.85 Impact Factor -
Chapter: Mapping genes on tammar wallaby target chromosomes
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ABSTRACT: This is an exciting time for marsupial genomics, with the release of the sequences of two marsupial genomes. One of these is the tammar wallaby, Australia’s model kangaroo, which has been the model macropod species for marsupial genetic studies for over 30 years. The tammar, and other marsupials, occupy a phylogenetic “sweet spot” between birds and eutherian mammals that is very valuable for genome comparisons. To anchor the tammar genome sequence, we are generating a physical map of genes on tammar chromosomes. Of particular interest to our laboratory are genes on chromosomes X and 5. Both of these chromosomes harbour genes that are found on the human X chromosome, many of which are essential to mammalian sex differentiation, reproduction and development. Mapping these genes will assist in tracing the evolutionary history of the mammalian X chromosome, identifying ancient and recently added regions. In addition, mapping genes to the tammar X will permit an intense study of marsupial X chromosome inactivation, a process that involves silencing one X chromosome in females to compensate for the difference in the number of X chromosomes between males and females. Marsupial X inactivation is different at the phenotypic and molecular level from inactivation in human and mouse, so investigations of the tammar X will help to deconstruct this complex process. Tammar chromosome 5 contains, in addition to genes found on the human X, gene blocks from other human chromosomes, and comparisons of gene organisation in this region between humans and other vertebrates have and will continue to provide insight into evolution of other regions of the mammalian genome.06/2010: pages 3-11; , ISBN: 9780643096622 -
Chapter: Organization and Evolution of the Marsupial X Chromosome
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ABSTRACT: Marsupial genomics and genetics provide invaluable data for comparative analysis because these mammals are distantly related cousins of humans and other eutherian mammals (∼148 million years), but they are more closely related to eutherians compared to monotremes (∼166 million years) and birds (∼310 million years). This divergence time places them uniquely on the phylogenetic tree whereby comparative gene mapping and genome sequences of marsupials enable us to trace the evolution of the therian X chromosome. It is shown by comparative gene mapping that the marsupial X chromosome is homologous to the long arm and pericentric region of the short arm of the human X chromosome (X conserved region). However, it is homologous to autosomes in the platypus and the chicken, suggesting that a novel XY system evolved in therian mammals after they diverged from monotremes 166 million years ago but before marsupials diverged from eutherians 148 million years ago. Apart from the X conserved region, eutherian mammals have an autosomal addition on the X chromosome (X added region) since their divergence from marsupials. Although the marsupial X chromosome is similar in composition to that of the eutherian X chromosome, it has accumulated numerous rearrangements, has become GC rich and has acquired a higher synonymous substitution rate since divergence of marsupial and eutherian mammals. Similarly, the marsupial X chromosome undergoes X inactivation like eutherian mammals, but the mechanisms, which regulates X inactivation, is very different from that observed in eutherian mammal, and may be the ancestral state. The XIST gene responsible for X inactivation in eutherian mammals is absent from the marsupial lineage suggesting that the evolution of XIST in early eutherians set up selection for accumulation of LINE sequences that aided the spread of X inactivation. Unlike the LINE accumulation on the eutherian X chromosome, the marsupial X has accumulated and expanded a microRNA family that could be involved in the marsupial X inactivation. This chapter provides a comprehensive review of the organization and evolution of the marsupial X chromosome and the implications this may have for X inactivation. KeywordsChromosome painting-Comparative genomics-Genome evolution-Karyotype-Sex chromosomes12/2009: pages 151-171; -
Article: Does the human X contain a third evolutionary block? Origin of genes on human Xp11 and Xq28.
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ABSTRACT: Comparative gene mapping of human X-borne genes in marsupials defined an ancient conserved region and a recently added region of the eutherian X, and the separate evolutionary origins of these regions was confirmed by their locations on chicken chromosomes 4p and 1q, respectively. However, two groups of genes, from the pericentric region of the short arm of the human X (at Xp11) and a large group of genes from human Xq28, were thought to be part of a third evolutionary block, being located in a single region in fish, but mapping to chicken chromosomes other than 4p and 1q. We tested this hypothesis by comparative mapping of genes in these regions. Our gene mapping results show that human Xp11 genes are located on the marsupial X chromosome and platypus chromosome 6, indicating that the Xp11 region was part of original therian X chromosome. We investigated the evolutionary origin of genes from human Xp11 and Xq28, finding that chicken paralogs of human Xp11 and Xq28 genes had been misidentified as orthologs, and their true orthologs are represented in the chicken EST database, but not in the current chicken genome assembly. This completely undermines the evidence supporting a separate evolutionary origin for this region of the human X chromosome, and we conclude, instead, that it was part of the ancient autosome, which became the conserved region of the therian X chromosome 166 million years ago.Genome Research 06/2009; 19(8):1350-60. · 13.61 Impact Factor -
Article: The evolution of the DLK1-DIO3 imprinted domain in mammals.
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ABSTRACT: A comprehensive, domain-wide comparative analysis of genomic imprinting between mammals that imprint and those that do not can provide valuable information about how and why imprinting evolved. The imprinting status, DNA methylation, and genomic landscape of the Dlk1-Dio3 cluster were determined in eutherian, metatherian, and prototherian mammals including tammar wallaby and platypus. Imprinting across the whole domain evolved after the divergence of eutherian from marsupial mammals and in eutherians is under strong purifying selection. The marsupial locus at 1.6 megabases, is double that of eutherians due to the accumulation of LINE repeats. Comparative sequence analysis of the domain in seven vertebrates determined evolutionary conserved regions common to particular sub-groups and to all vertebrates. The emergence of Dlk1-Dio3 imprinting in eutherians has occurred on the maternally inherited chromosome and is associated with region-specific resistance to expansion by repetitive elements and the local introduction of noncoding transcripts including microRNAs and C/D small nucleolar RNAs. A recent mammal-specific retrotransposition event led to the formation of a completely new gene only in the eutherian domain, which may have driven imprinting at the cluster.PLoS Biology 07/2008; 6(6):e135. · 11.45 Impact Factor -
Article: Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals.
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ABSTRACT: Vertebrate alpha (alpha)- and beta (beta)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the alpha- and beta-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil beta-globin gene (omega) in the marsupial alpha-cluster, however, suggested that duplication of the alpha-beta cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous alpha- and beta-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. The platypus alpha-globin cluster (chromosome 21) contains embryonic and adult alpha- globin genes, a beta-like omega-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-zeta-zeta'-alphaD-alpha3-alpha2-alpha1-omega-GBY-3'. The platypus beta-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-epsilon-beta-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate alpha-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal beta-globin clusters are embedded in olfactory genes. Thus, the mammalian alpha- and beta-globin clusters are orthologous to the bird alpha- and beta-globin clusters respectively. We propose that alpha- and beta-globin clusters evolved from an ancient MPG-C16orf35-alpha-beta-GBY-LUC7L arrangement 410 million years ago. A copy of the original beta (represented by omega in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago), then duplicated and diverged to form orthologous clusters of beta-globin genes with different expression profiles in different lineages.BMC Biology 01/2008; 6:34. · 5.75 Impact Factor -
Article: Search for the sex-determining switch in monotremes: mapping WT1, SF1, LHX1, LHX2, FGF9, WNT4, RSPO1 and GATA4 in platypus.
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ABSTRACT: The duck-billed platypus has five pairs of sex chromosomes, but there is no information about the primary sex-determining switch in this species. As there is no apparent SRY orthologue in platypus, another gene must acquire the function of a key regulator of the gonadal male or female fate. SOX9 was ruled out from being this key regulator as it maps to an autosome in platypus. To check whether other genes in mammalian gonadogenesis could be the primary switch in monotremes, we have mapped a number of candidates in platypus. We report here the autosomal location of WT1, SF1, LHX1, LHX9, FGF9, WNT4 and RSPO1 in platypus, thus excluding these from being key regulators of sex determination in this species. We found that GATA4 maps to sex chromosomes Y1 and X2; however, it lies in the pairing region shown by chromosome painting to be homologous, so is unlikely to be either male-specific or differentially dosed in male and female.Chromosome Research 02/2007; 15(6):777-85. · 3.09 Impact Factor -
Article: The multiple sex chromosomes of platypus and echidna are not completely identical and several share homology with the avian Z.
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ABSTRACT: Sex-determining systems have evolved independently in vertebrates. Placental mammals and marsupials have an XY system, birds have a ZW system. Reptiles and amphibians have different systems, including temperature-dependent sex determination, and XY and ZW systems that differ in origin from birds and placental mammals. Monotremes diverged early in mammalian evolution, just after the mammalian clade diverged from the sauropsid clade. Our previous studies showed that male platypus has five X and five Y chromosomes, no SRY, and DMRT1 on an X chromosome. In order to investigate monotreme sex chromosome evolution, we performed a comparative study of platypus and echidna by chromosome painting and comparative gene mapping. Chromosome painting reveals a meiotic chain of nine sex chromosomes in the male echidna and establishes their order in the chain. Two of those differ from those in the platypus, three of the platypus sex chromosomes differ from those of the echidna and the order of several chromosomes is rearranged. Comparative gene mapping shows that, in addition to bird autosome regions, regions of bird Z chromosomes are homologous to regions in four platypus X chromosomes, that is, X1, X2, X3, X5, and in chromosome Y1. Monotreme sex chromosomes are easiest to explain on the hypothesis that autosomes were added sequentially to the translocation chain, with the final additions after platypus and echidna divergence. Genome sequencing and contig anchoring show no homology yet between platypus and therian Xs; thus, monotremes have a unique XY sex chromosome system that shares some homology with the avian Z.Genome biology 02/2007; 8(11):R243. · 6.63 Impact Factor -
Article: Characterisation of the marsupial-specific ATRY gene: implications for the evolution of male-specific function.
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ABSTRACT: Many or most genes on the mammal Y chromosome evolved a testis-specific function after diverging from an X-borne copy with a general function in both sexes. In marsupial but not eutherian mammals, a testis-specific orthologue (ATRY) of the widely expressed X-borne ATRX gene lies on the Y chromosome. Since mutations in human ATRX cause sex reversal, it is possible that one function of ATRY in marsupials is testicular differentiation. We report here the isolation and sequencing of the tammar wallaby (Macropus eugenii) ATRY cDNA, and comparison of its sequence with that of tammar ATRX. The evolution of a testis-specific function for the ATRY protein distinct from the general role of ATRX in both sexes has been accompanied by sequence changes in many protein domains that would alter protein binding partners. A large open reading frame encodes a 1771 amino acid ATRY protein that has diverged extensively from ATRX. The conservation and loss of particular motifs identify those required for testicular function (ATRY) and function in other tissues (ATRX).Gene 01/2006; 362:29-36. · 2.34 Impact Factor -
Article: Marsupials and monotremes sort genome treasures from junk.
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ABSTRACT: A recent landmark paper demonstrates the unique contribution of marsupials and monotremes to comparative genome analysis, filling an evolutionary gap between the eutherian mammals (including humans) and more distant vertebrate species.Genome biology 02/2005; 6(5):218. · 6.63 Impact Factor -
Article: Resolution and evolution of the duck-billed platypus karyotype with an X1Y1X2Y2X3Y3X4Y4X5Y5 male sex chromosome constitution.
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ABSTRACT: The platypus (2n = 52) has a complex karyotype that has been controversial over the last three decades. The presence of unpaired chromosomes and an unknown sex-determining system especially has defied attempts at conventional analysis. This article reports on the preparation of chromosome-specific probes from flow-sorted chromosomes and their application in the identification and classification of all platypus chromosomes. This work reveals that the male karyotype has 21 pairs of chromosomes and 10 unpaired chromosomes (E1-E10), which are linked by short regions of homology to form a multivalent chain in meiosis. The female karyotype differs in that five of these unpaired elements (E1, E3, E5, E7, and E9) are each present in duplicate, whereas the remaining five unpaired elements (E2, E4, E6, E8, and E10) are absent. This finding indicates that sex is determined by the alternate segregation of the chain of 10 during spermatogenesis so that equal numbers of sperm bear either one of the two groups of five elements, i.e., five X and five Y chromosomes. Chromosome painting reveals that these X and Y chromosomes contain pairing (XY shared) and differential (X- or Y-specific) segments. Y differential regions must contain male-determining genes, and X differential regions should be dosage-compensated in the female. Two models for the evolution of the sex-determining system are presented. The resolution of the longstanding debate over the platypus karyotype is an important step toward the understanding of mechanisms of sex determination, dosage compensation, and karyotype evolution.Proceedings of the National Academy of Sciences 12/2004; 101(46):16257-61. · 9.68 Impact Factor -
Article: Marsupial anti-Mullerian hormone gene structure, regulatory elements, and expression.
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ABSTRACT: During male sexual development in reptiles, birds, and mammals, anti-Müllerian hormone (AMH) induces the regression of the Müllerian ducts that normally form the primordia of the female reproductive tract. Whereas Müllerian duct regression occurs during fetal development in eutherian mammals, in marsupial mammals this process occurs after birth. To investigate AMH in a marsupial, we isolated an orthologue from the tammar wallaby (Macropus eugenii) and characterized its expression in the testes and ovaries during development. The wallaby AMH gene is highly conserved with the eutherian orthologues that have been studied, particularly within the encoded C-terminal mature domain. The N-terminus of marsupial AMH is divergent and larger than that of eutherian species. It is located on chromosome 3/4, consistent with its autosomal localization in other species. The wallaby 5' regulatory region, like eutherian AMH genes, contains binding sites for SF1, SOX9, and GATA factors but also contains a putative SRY-binding site. AMH expression in the developing testis begins at the time of seminiferous cord formation at 2 days post partum, and Müllerian duct regression begins shortly afterward. In the developing testis, AMH is localized in the cytoplasm of the Sertoli cells but is lost by adulthood. In the developing ovary, there is no detectable AMH expression, but in adults it is produced by the granulosa cells of primary and secondary follicles. It is not detectable in atretic follicles. Collectively, these studies suggest that AMH expression has been conserved during mammalian evolution and is intimately linked to upstream sex determination mechanisms.Biology of Reproduction 02/2004; 70(1):160-7. · 4.01 Impact Factor -
Article: Comparative Genome Maps of Vertebrates (Enclosed poster).
ILAR journal / National Research Council, Institute of Laboratory Animal Resources 02/1998; 39(2-3):INSERT. · 2.33 Impact Factor -
Article: Comparative Chromosome Painting (Enclosed poster).
ILAR journal / National Research Council, Institute of Laboratory Animal Resources 02/1998; 39(2-3):INSERT. · 2.33 Impact Factor -
Article: Characterisation of the marsupial-specific ATRY gene: Implications for the evolution of male-specific function
[show abstract] [hide abstract]
ABSTRACT: Many or most genes on the mammal Y chromosome evolved a testis-specific function after diverging from an X-borne copy with a general function in both sexes. In marsupial but not eutherian mammals, a testis-specific orthologue (ATRY) of the widely expressed X-borne ATRX gene lies on the Y chromosome. Since mutations in human ATRX cause sex reversal, it is possible that one function of ATRY in marsupials is testicular differentiation. We report here the isolation and sequencing of the tammar wallaby (Macropus eugenii) ATRY cDNA, and comparison of its sequence with that of tammar ATRX. The evolution of a testis-specific function for the ATRY protein distinct from the general role of ATRX in both sexes has been accompanied by sequence changes in many protein domains that would alter protein binding partners. A large open reading frame encodes a 1771 amino acid ATRY protein that has diverged extensively from ATRX. The conservation and loss of particular motifs identify those required for testicular function (ATRY) and function in other tissues (ATRX).Gene.
Top co-authors
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Institutions
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2004–2009
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Australian National University
Canberra, Australian Capital Territory, Australia
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2004–2007
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University of Cambridge
- Department of Veterinary Medicine
Cambridge, ENG, United Kingdom
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1998–2006
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University of Melbourne
- Department of Zoology
Melbourne, Victoria, Australia
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