Mammalian chromodomain proteins: their role in genome organisation and expression

The chromodomain is a highly conserved sequence motif that has been identified in a variety of animal and plant species. In mammals, chromodomain proteins appear to be either structural components of large macromolecular chromatin complexes or proteins involved in remodelling chromatin structure. Recent work has suggested that apart from a role in regulating gene activity, chromodomain proteins may also play roles in genome organisation. This article reviews progress made in characterising mammalian chromodomain proteins and emphasises their emerging role in the regulation of gene expression and genome organisation. BioEssays 22:124-137, 2000.     

Mammalian sex-chromosome evolution: a conserved homoeologous segment on the X and Y chromosomes in primates

In a representative sample of primate species, including simians (Catarrhini and Platyrrhini) and prosimians (Lemuriformes and Lorisiformes), high-resolution, early replication banding revealed a homoeologous early replicating segment at the ends of both sex chromosomes. The DXYZ2 element, a repeated sequence specific for the human pseudoautosomal region, is conserved in the genomes of all primate species studies and is specifically localized in the distal early replicating segments of the X and Y chromosomes. Thus, cytogenetic and molecular evidence is presented of a highly conserved sex-chromosomal segment in primates. The pseudoautosomal behavior of this segment is discussed.     

The evolution of eutherian chromosomes

The gross organization of the genome of Eutheria (placental mammals) into chromosomes follows a simple architecture that, with some minor changes, is almost completely conserved for more than 100 million years in various species of almost all extant mammalian orders. Recent molecular cytogenetic results--especially those from the assumed oldest clade, the Afrotheria--suggest an ancestral karyotype that would calculate the "default" frequency of gross rearrangements to less than two changes within 10 million years of mammalian evolution. The main changes are the fission, movement and subsequent fusion of large chromosome segments or of chromosome arms. Reciprocal translocations are the exception. Chromosome numbers may have increased or decreased significantly in this fusion/fission process but, in most instances, the main architecture still remains evident. There are, however, some exceptions in mammals with extremely derived karyotypes.     

The evolution of sex chromosomes

Mammalian sex chromosomes appear, behave and function differently than the autosomes, passing on their genes in a unique sex-linked manner. The publishing of Ohno's hypothesis provided a framework for discussion of sex chromosome evolution, allowing it to be developed and challenged numerous times. In this report we discuss the pressures that drove the evolution of sex and the mechanisms by which it occurred. We concentrate on how the sex chromosomes evolved in mammals, discussing the various hypotheses proposed and the evidence supporting them.     

The origin and evolution of sex chromosomes,revealed by sequencing of the Silene latifolia female genome

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The evolution of marsupial and monotreme chromosomes

Marsupial and monotreme mammals fill an important gap in vertebrate phylogeny between reptile-mammal divergence 310 million years ago (mya) and the eutherian (placental) mammal radiation 105 mya. They possess many unique features including their distinctive chromosomes, which in marsupials are typically very large and well conserved between species. In contrast, monotreme genomes are divided into several large chromosomes and many smaller chromosomes, with a complicated sex chromosome system that forms a translocation chain in male meiosis. The application of molecular cytogenetic techniques has greatly advanced our understanding of the evolution of marsupial chromosomes and allowed the reconstruction of the ancestral marsupial karyotype. Chromosome painting and gene mapping have played a vital role in piecing together the puzzle of monotreme karyotypes, particularly their complicated sex chromosome system. Here, we discuss the significant insight into karyotype evolution afforded by the combination of recently sequenced marsupial and monotreme genomes with cytogenetic analysis, which has provided a greater understanding of the events that have shaped not only marsupial and monotreme genomes, but the genomes of all mammals.     

Mammalian genome evolution: new clues from comparisons of eutherians, marsupials and monotremes.

1. Comparisons of chromosomes and gene maps of different mammals are yielding a big picture of the evolution of mammalian genome form and function. It has been particularly instructive to compare gene arrangements on the sex chromosomes between the three major groups of mammals. Eutheria (so-called placental mammals). Metatheria (marsupials) and Prototheria (monotremes), which diverged 150 and 170 Myr BP respectively. 2. A region amounting to 3% of the haploid genome is located on the X chromosome in all three groups, implying that this region must have been part of the original X in a common ancestor. This region comprises the long arm of the human X. 3. A region represented by the short arm of the human X is common to the X in all eutherians, but is autosomal in marsupials and monotremes; thus it was not a part of the original X, and must have been acquired by the X early in the eutherian radiation. 4. This recently acquired region was probably translocated to a pseudoautosomal region shared by the eutherian X and Y. Thus it was originally paired and exempt from X chromosome inactivation; stepwise deletion of this region from the Y and recruitment of the newly unpaired region of the X into the inactivation system could account for some of the peculiarities of this region of the human X. 5. The sex-determining gene TDF must lie on the Y in all mammals in which the Y is male determining. The autosomal location of the candidate gene ZFY in marsupials and monotremes eliminates it from consideration. The recently described candidate gene SRY has yet to pass the "marsupial test".     

The fate of recombinant chromosomes and genome interaction in Nicotiana asymmetric somatic hybrids and their sexual progeny

Genomic in-situ hybridization (GISH) was used to monitor the behaviour of parental genomes, and the fate of intergenomic chromosome translocations, through meiosis of plants regenerated from asymmetric somatic hybrids between Nicotiana sylvestris and N. plumbaginifolia. Meiotic pairing in the regenerants was exclusively between chromosomes or chromosome segments derived from the same species. Translocation (recombinant) chromosomes contained chromosome segments from both parental species, and were detected at all stages of meiosis. They occasionally paired with respectively homologous segments of N. sylvestris or N. plumbaginifolia chromosomes. Within hybrid nuclei, the meiotic division of N. plumbaginifolia lagged behind that of N. sylvestris. However, normal and recombinant chromosomes were eventually incorporated into dyads and tetrads, and the regenerants were partially pollen fertile. Recombinant chromosomes were transmitted through either male or female gametes, and were detected by GISH in sexual progeny obtained on selfing or backcrossing the regenerants to N. sylvestris. A new recombinant chromosome in one plant of the first backcross generation provided evidence of further chromosome rearrangements occurring at, or following, meiosis in the original regenerants. This study demonstrates the stable incorporation of chromosome segments from one parental genome of an asymmetric somatic hybrid into another, via intergenomic translocation, and reveals their transmission to subsequent sexual progeny.     

Isolation of individual chromosomes and their use in studying the human and animal genome

This mini-review considers the main achievements in the field of human and animal chromosome separation: technical problems of flow-karyotyping and flow-sorting, the types of cell lines and chromosome source used, different protocols of chromosome suspension preparation, fluorochromes for chromosome staining, efficiency of chromosome sorting and purity of the fractions. The use of fractions for creating chromosome-specific human gene libraries and mapping cloned genes and DNA fragment are also considered.     

Higher-order genome organization in platypus and chicken sperm and repositioning of sex chromosomes during mammalian evolution

In mammals, chromosomes occupy defined positions in sperm, whereas previous work in chicken showed random chromosome distribution. Monotremes (platypus and echidnas) are the most basal group of living mammals. They have elongated sperm like chicken and a complex sex chromosome system with homology to chicken sex chromosomes. We used platypus and chicken genomic clones to investigate genome organization in sperm. In chicken sperm, about half of the chromosomes investigated are organized non-randomly, whereas in platypus chromosome organization in sperm is almost entirely non-random. The use of genomic clones allowed us to determine chromosome orientation and chromatin compaction in sperm. We found that in both species chromosomes maintain orientation of chromosomes in sperm independent of random or non-random positioning along the sperm nucleus. The distance of loci correlated with the total length of sperm nuclei, suggesting that chromatin extension depends on sperm elongation. In platypus, most sex chromosomes cluster in the posterior region of the sperm nucleus, presumably the result of postmeiotic association of sex chromosomes. Chicken and platypus autosomes sharing homology with the human X chromosome located centrally in both species suggesting that this is the ancestral position. This suggests that in some therian mammals a more anterior position of the X chromosome has evolved independently.     

The widespread nature of Pack-TYPE transposons reveals their importance for plant genome evolution

Pack-TYPE transposable elements (TEs) are a group of non-autonomous DNA transposons found in plants. These elements can efficiently capture and shuffle coding DNA across the host genome, accelerating the evolution of genes. Despite their relevance for plant genome plasticity, the detection and study of Pack-TYPE TEs are challenging due to the high similarity these elements have with genes. Here, we produced an automated annotation pipeline designed to study Pack-TYPE elements and used it to successfully annotate and analyse more than 10,000 new Pack-TYPE TEs in the rice and maize genomes. Our analysis indicates that Pack-TYPE TEs are an abundant and heterogeneous group of elements. We found that these elements are associated with all main superfamilies of Class II DNA transposons in plants and likely share a similar mechanism to capture new chromosomal DNA sequences. Furthermore, we report examples of the direct contribution of these TEs to coding genes, suggesting a generalised and extensive role of Pack-TYPE TEs in plant genome evolution.     

Mammalian sex chromosomes: Evolution of organization and function

Comparisons of chromosome size, morphology and gene arrangements between mammals of different species permit us to deduce the genome characteristics of the common ancestor, and to chart the changes that have occurred during the divergence of the two lineages. The more distantly related are the species compared, the more remote the common ancestor whose characteristics can be deduced. This means that, providing there are sufficient similarities to warrant comparison, the more divergent the species compared, the more significant the contribution to our understanding of the organization of an ancestral mammalian genome and the process of mammalian genome evolution. One of the genetic surprises of the last decade was the discovery that, although gross karyotypes of distantly related orders of eutherian mammals (e.g. cat, cow, rabbit, man) have diverged extensively, gene mapping studies reveal the presence of large chromosome segments conserved across at least 60 million years (O'Brien et al. 1988). This finding makes it worthwhile to extend genetic comparisons to the two groups of mammals most distantly related to eutherian mammals--marsupials and monotremes. Here we will review comparisons of the sex chromosomes in these three major groups of extant mammals, and show how they have led us to a new view of the evolution of mammalian sex chromosome organization and function in sex determination and X chromosome inactivation.     

Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution

Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.