The origin and evolution of vertebrate sex chromosomes and dosage compensation.

In mammals, birds, snakes and many lizards and fish, sex is determined genetically (either male XY heterogamy or female ZW heterogamy), whereas in alligators, and in many reptiles and turtles, the temperature at which eggs are incubated determines sex. Evidently, different sex-determining systems (and sex chromosome pairs) have evolved independently in different vertebrate lineages. Homology shared by Xs and Ys (and Zs and Ws) within species demonstrates that differentiated sex chromosomes were once homologous, and that the sex-specific non-recombining Y (or W) was progressively degraded. Consequently, genes are left in single copy in the heterogametic sex, which results in an imbalance of the dosage of genes on the sex chromosomes between the sexes, and also relative to the autosomes. Dosage compensation has evolved in diverse species to compensate for these dose differences, with the stringency of compensation apparently differing greatly between lineages, perhaps reflecting the concentration of genes on the original autosome pair that required dosage compensation. We discuss the organization and evolution of amniote sex chromosomes, and hypothesize that dosage insensitivity might predispose an autosome to evolving function as a sex chromosome.

Conservation of a chromosome arm in two distantly related marsupial species.

Marsupials, which diverged from eutherian mammals 150 million years ago (MYA), occupy a phylogenetic position that is very valuable in genome comparisons of mammal and other vertebrate species. Within the marsupials, the Australian and American clades (represented by the tammar wallaby Macropus eugenii, and the opossum Monodelphis domestica) diverged about 70 MYA. G-banding and chromosome painting suggest that tammar wallaby chromosome 6q has homology to opossum chromosome 7q. We tested this conservation by physically mapping the tammar wallaby orthologs of opossum chromosome 7q genes. We isolated 28 tammar wallaby BAC clones that contained orthologs of 16 opossum chromosome 7q genes. We used fluorescence in situ hybridization (FISH) to show that they all mapped specifically to the tammar wallaby chromosome 6q in nearly the same order as their orthologs on opossum chromosome 7q. Thus this chromosome arm is genetically, as well as cytologically, conserved over the 55-80 million years that separate kangaroos and the opossum.

Sex determination in mammals--before and after the evolution of SRY.

Therian mammals (marsupials and placentals) have an XX female: XY male sex chromosome system, which is homologous to autosomes in other vertebrates. The testis-determining gene, SRY, is conserved on the Y throughout therians, but is absent in other vertebrates, suggesting that the mammal system evolved about 310 million years ago (MYA). However, recent work on the basal monotreme mammals has completely changed our conception of how and when this change occurred. Platypus and echidna lack SRY, and the therian X and Y are represented by autosomes, implying that SRY evolved in therians after their divergence from monotremes only 166 MYA. Clues to the ancestral mechanism usurped by SRY in therians are provided by the monotremes, whose sex chromosomes are homologous to the ZW of birds. This suggests that the therian X and Y, and the SRY gene, evolved from an ancient bird-like sex chromosome system which predates the divergence of mammals and reptiles 310 MYA.

Dissection of a Y-autosome translocation in Cryptomys hottentotus (Rodentia, Bathyergidae) and implications for the evolution of a meiotic sex chromosome chain.

We describe the outcome of a comprehensive cytogenetic survey of the common mole-rat, Cryptomys hottentotus, based on G and C banding, fluorescence in situ hybridisation and the analysis of meiotic chromosomes using immunostaining of proteins involved in the formation of synaptonemal complex (SCP1 and SCP3). We identified the presence of a Y-autosome translocation that is responsible for a fixed diploid number difference between males (2n = 53) and females (2n = 54), a character that likely defines the C. hottentotus lineage. Immunostaining, combined with C banding of spermatocytes, revealed a linearised sex trivalent with X(1) at one end and X(2) at the other, with evidence of reduced recombination between Y and X(2) that seems to be heterochromatin dependant in the C. hottentotus lineage. We suggest that this could depict the likely initial step in the differentiation of a true neo-X, and that this may mimic an early stage in the mammalian meiotic chain formation, an evolutionary process that has been taken to an extreme in a monotreme mammal, the platypus.

Sex determination in platypus and echidna: autosomal location of SOX3 confirms the absence of SRY from monotremes.

In eutherian ('placental') mammals, sex is determined by the presence or absence of the Y chromosome-borne gene SRY, which triggers testis determination. Marsupials also have a Y-borne SRY gene, implying that this mechanism is ancestral to therians, the SRY gene having diverged from its X-borne homologue SOX3 at least 180 million years ago. The rare exceptions have clearly lost and replaced the SRY mechanism recently. Other vertebrate classes have a variety of sex-determining mechanisms, but none shares the therian SRY-driven XX female:XY male system. In monotreme mammals (platypus and echidna), which branched from the therian lineage 210 million years ago, no orthologue of SRY has been found. In this study we show that its partner SOX3 is autosomal in platypus and echidna, mapping among human X chromosome orthologues to platypus chromosome 6, and to the homologous chromosome 16 in echidna. The autosomal localization of SOX3 in monotreme mammals, as well as non-mammal vertebrates, implies that SRY is absent in Prototheria and evolved later in the therian lineage 210-180 million years ago. Sex determination in platypus and echidna must therefore depend on another male-determining gene(s) on the Y chromosomes, or on the different dosage of a gene(s) on the X chromosomes.

Cloning and mapping of platypus SOX2 and SOX14: insights into SOX group B evolution.

Group B SOX genes, the closest relatives to the sex-determining gene SRY, are thought to have evolved from a single ancestral SOX B by a series of duplications and translocations. The two SOX B genes SOX2 and SOX14 co-localize to chromosome 3q in humans. SOX2 and SOX14 homologues were cloned and characterized in the platypus, a monotreme mammal distantly related to man. The two genes were found to co-localize to chromosome 1q in this species. Proximity of the two related genes has therefore been conserved for 170 Myr, since humans and platypus diverged. The sequence similarity and conserved synteny of these group B genes provide clues to their origin. A simple model of SOX group B gene evolution is proposed.

The human Y chromosome derives largely from a single autosomal region added to the sex chromosomes 80-130 million years ago.

Mapping of human X-borne genes in distantly related mammals has defined a conserved region shared by the X chromosome in all three extant mammalian groups, plus a region that was recently added to the eutherian X but is still autosomal in marsupials and monotremes. Using comparative mapping of human Y-borne genes, we now directly show that the eutherian Y is also composed of a conserved and an added region which contains most of the ubiquitously expressed Y-borne genes. Little of the ancient conserved region remains, and the human Y chromosome is largely derived from the added region.