Chromosome evolution in malaria mosquitoes

The genomic era offers excellent opportunities to improve our understanding of the genetic basis of mosquito adaptation, evolution, and competence to a pathogen. The availability of polytene chromosomes in anopheline mosquitoes makes them an excellent model system for studying genome organization, evolution, and function. Physical mapping facilitated the whole genome sequence assembly for the major malaria vector Anopheles gambiae and comparative genome mapping has determined types, patterns, and rates of chromosomal rearrangements in mosquito evolution. Together with sequencing projects, high-resolution physical mapping can shed light on mechanisms of chromosomal rearrangements and phylogenetic relation-ships among species.     

Multiple cellular mechanisms prevent chromosomal rearrangements involving repetitive DNA

Repetitive DNA is present in the eukaryotic genome in the form of segmental duplications, tandem and interspersed repeats, and satellites. Repetitive sequences can be beneficial by serving specific cellular functions (e.g. centromeric and telomeric DNA) and by providing a rapid means for adaptive evolution. However, such elements are also substrates for deleterious chromosomal rearrangements that affect fitness and promote human disease. Recent studies analyzing the role of nuclear organization in DNA repair and factors that suppress non-allelic homologous recombination (NAHR) have provided insights into how genome stability is maintained in eukaryotes. In this review, we outline the types of repetitive sequences seen in eukaryotic genomes and how recombination mechanisms are regulated at the DNA sequence, cell organization, chromatin structure, and cell cycle control levels to prevent chromosomal rearrangements involving these sequences.     

Multiple cellular mechanisms prevent chromosomal rearrangements involving repetitive DNA

Repetitive DNA is present in the eukaryotic genome in the form of segmental duplications, tandem and interspersed repeats, and satellites. Repetitive sequences can be beneficial by serving specific cellular functions (e.g. centromeric and telomeric DNA) and by providing a rapid means for adaptive evolution. However, such elements are also substrates for deleterious chromosomal rearrangements that affect fitness and promote human disease. Recent studies analyzing the role of nuclear organization in DNA repair and factors that suppress non-allelic homologous recombination (NAHR) have provided insights into how genome stability is maintained in eukaryotes. In this review, we outline the types of repetitive sequences seen in eukaryotic genomes and how recombination mechanisms are regulated at the DNA sequence, cell organization, chromatin structure, and cell cycle control levels to prevent chromosomal rearrangements involving these sequences.     

Tracing the evolution of amniote chromosomes

A great deal of diversity in chromosome number and arrangement is observed across the amniote phylogeny. Understanding how this diversity is generated is important for determining the role of chromosomal rearrangements in generating phenotypic variation and speciation. Gaining this understanding is achieved by reconstructing the ancestral genome arrangement based on comparisons of genome organization of extant species. Ancestral karyotypes for several amniote lineages have been reconstructed, mainly from cross-species chromosome painting data. The availability of anchored whole genome sequences for amniote species has increased the evolutionary depth and confidence of ancestral reconstructions from those made solely from chromosome painting data. Nonetheless, there are still several key lineages where the appropriate data required for ancestral reconstructions is lacking. This review highlights the progress that has been made towards understanding the chromosomal changes that have occurred during amniote evolution and the reconstruction of ancestral karyotypes.     

Chromosomal rearrangements breakpoints clusterization: is the clonal selection involved

Certain types of cancer are often correlate with certain chromosomal rearrangements. The chimaeric genes are formed as a result of this rearrangements, and the chimaeric proteins are the products of their expression. The breakpoints of such translocation are often clustered in the genome. Moreover, such breakpoint clusters often contain specific genomic elements like topoisomerase II consensus sites, nuclear matrix attachment regions and DNA sequences, which can make up secondary non-canonical structure. In this review we discuss whether breakpoints may be induced by chromatin structure. Furthermore, we bring up not touched upon literature question about the relation between the breakpoint clusters and the domain organization of corresponding proteins. We also consider possible mechanisms of chromosomal rearrangements.     

Sequence Features Contributing to Chromosomal Rearrangements in Neisseria gonorrhoeae

Through whole genome sequence alignments, breakpoints in chromosomal synteny can be identified and the sequence features associated with these determined. Alignments of the genome sequences of Neisseria gonorrhoeae strain FA1090, N. gonorrhoeae strain NCCP11945, and N. gonorrhoeae strain TCDC-NG08107 reveal chromosomal rearrangements that have occurred. Based on these alignments and dot plot pair-wise comparisons, the overall chromosomal arrangement of strain NCCP11945 and TCDC-NG08107 are very similar, with no large inversions or translocations. The insertion of the Gonococcal Genetic Island in strain NCCP11945 is the most prominent distinguishing feature differentiating these strains. When strain NCCP11945 is compared to strain FA1090, however, 14 breakpoints in chromosomal synteny are identified between these gonococcal strains. The majority of these, 11 of 14, are associated with a prophage, IS elements, or IS-like repeat enclosed elements which appear to have played a role in the rearrangements observed. Additional rearrangements of small regions of the genome are associated with pilin genes. Evidence presented here suggests that the rearrangements of blocks of sequence are mediated by activation of prophage and associated IS elements and reintegration elsewhere in the genome or by homologous recombination between IS-like elements that have generated inversions.     

Genome evolution in Arabidopsis/Brassica: conservation and divergence of ancient rearranged segments and their breakpoints

Since the tetraploidization of the Arabidopsis thaliana ancestor 30-35 million years ago (Mya), a wave of chromosomal rearrangements have modified its genome architecture. The dynamics of this process is unknown, as it has so far been impossible to date individual rearrangement events. In this paper, we present evidence demonstrating that the majority of rearrangements occurred before the Arabidopsis-Brassica split 20-24 Mya, and that the segmental architecture of the A. thaliana genome is predominantly conserved in Brassica. This finding is based on the conservation of four rearrangement breakpoints analysed by fluorescence in situ hybridization (FISH) and RFLP mapping of three A. thaliana chromosomal regions. For this purpose, 95 Arabidopsis bacterial artificial chromosomes (BACs) spanning a total of 8.25 Mb and 81 genetic loci for 36 marker genes were studied in the Brassica oleracea genome. All the regions under study were triplicated in the B. oleracea genome, confirming the hypothesis of Brassica ancestral genome triplication. However, whilst one of the breakpoints was conserved at one locus, it was not at the two others. Further comparison of their organization may indicate that the evolution of the hexaploid Brassica progenitor proceeded by several events, separated in time. Genetic mapping and reprobing with rDNA allowed assignment of the regions to particular Brassica chromosomes. Based on this study of regional organization and evolution, a new insight into polyploidization/diploidization cycles is proposed.     

Accumulating postzygotic isolation genes in parapatry: a new twist on chromosomal speciation

Chromosomal rearrangements can promote reproductive isolation by reducing recombination along a large section of the genome. We model the effects of the genetic barrier to gene flow caused by a chromosomal rearrangement on the rate of accumulation of postzygotic isolation genes in parapatry. We find that, if reproductive isolation is produced by the accumulation in parapatry of sets of alleles compatible within but incompatible across species, chromosomal rearrangements are far more likely to favor it than classical genetic barriers without chromosomal changes. New evidence of the role of chromosomal rearrangements in parapatric speciation suggests that postzygotic isolation is often due to the accumulation of such incompatibilities. The model makes testable qualitative predictions about the genetic signature of speciation.     

Phylogenomics of several deer species revealed by comparative chromosome painting with Chinese muntjac paints

A set of Chinese muntjac (Muntiacus reevesi) chromosome-specific paints has been hybridized onto the metaphases of sika deer (Cervus nippon, CNI, 2n = 66), red deer (Cervus elaphus, CEL, 2n = 62) and tufted deer (Elaphodus cephalophus, ECE, 2n = 47). Thirty-three homologous autosomal segments were detected in genomes of sika deer and red deer, while 31 autosomal homologous segments were delineated in genome of tufted deer. The Chinese muntjac chromosome X probe painted to the whole X chromosome, and the chromosome Y probe gave signals on the Y chromosome as well as distal region of the X chromosome of each species. Our results confirmed that exclusive Robertsonian translocations have contributed to the karyotypic evolution of sika deer and red deer. In addition to Robertsonian translocation, tandem fusions have played a more important role in the karyotypic evolution of tufted deer. Different types of chromosomal rearrangements have led to great differences in the genome organization between cervinae and muntiacinae species. Our analysis testified that six chromosomal fissions in the proposed 2n = 58 ancestral pecoran karyotype led to the formation of 2n = 70 ancestral cervid karyotype and the deer karyotypes is more derived compare with those of bovid species. Combining previous cytogenetic and molecular systematic studies, we analyzed the genome phylogeny for 11 cervid species.     

Chromatin loops,illegitimate recombination,and genome evolution

Chromosomal rearrangements frequently occur at specific places (“hot spots”) in the genome. These recombination hot spots are usually separated by 50–100 kb regions of DNA that are rarely involved in rearrangements. It is quite likely that there is a correlation between the above‐mentioned distances and the average size of DNA loops fixed at the nuclear matrix. Recent studies have demonstrated that DNA loop anchorage regions can be fairly long and can harbor DNA recombination hot spots. We previously proposed that chromosomal DNA loops may constitute the basic units of genome organization in higher eukaryotes. In this review, we consider recombination between DNA loop anchorage regions as a possible source of genome evolution.     

Conservation of chromosomes syntenic with avian autosomes in squamate reptiles revealed by comparative chromosome painting

In contrast to mammals, birds exhibit a slow rate of chromosomal evolution. It is not clear whether high chromosome conservation is an evolutionary novelty of birds or was inherited from an earlier avian ancestor. The evolutionary conservatism of macrochromosomes between birds and turtles supports the latter possibility; however, the rate of chromosomal evolution is largely unknown in other sauropsids. In squamates, we previously reported strong conservatism of the chromosomes syntenic with the avian Z, which could reflect a peculiarity of this part of the genome. The chromosome 1 of iguanians and snakes is largely syntenic with chromosomes 3, 5 and 7 of the avian ancestral karyotype. In this project, we used comparative chromosome painting to determine how widely this synteny is conserved across nine families covering most of the main lineages of Squamata. The results suggest that the association of the avian ancestral chromosomes 3, 5 and 7 can be dated back to at least the early Jurassic and could be an ancestral characteristic for Unidentata (Serpentes, Iguania, Anguimorpha, Laterata and Scinciformata). In Squamata chromosome conservatism therefore also holds for the parts of the genome which are homologous to bird autosomes, and following on from this, a slow rate of chromosomal evolution could be a common characteristic of all sauropsids. The large evolutionary stasis in chromosome organization in birds therefore seems to be inherited from their ancestors, and it is particularly striking in comparison with mammals, probably the only major tetrapod lineage with an increased rate of chromosomal rearrangements as a whole.     

Comparative Analysis of DNA Replication Timing Reveals Conserved Large-Scale Chromosomal Architecture

Recent evidence suggests that the timing of DNA replication is coordinated across megabase-scale domains in metazoan genomes, yet the importance of this aspect of genome organization is unclear. Here we show that replication timing is remarkably conserved between human and mouse, uncovering large regions that may have been governed by similar replication dynamics since these species have diverged. This conservation is both tissue-specific and independent of the genomic G+C content conservation. Moreover, we show that time of replication is globally conserved despite numerous large-scale genome rearrangements. We systematically identify rearrangement fusion points and demonstrate that replication time can be locally diverged at these loci. Conversely, rearrangements are shown to be correlated with early replication and physical chromosomal proximity. These results suggest that large chromosomal domains of coordinated replication are shuffled by evolution while conserving the large-scale nuclear architecture of the genome.     

Intrachromosomal rearrangements in avian genome evolution: evidence for regions prone to breakpoints

It is generally believed that the organization of avian genomes remains highly conserved in evolution as chromosome number is constant and comparative chromosome painting demonstrated there to be very few interchromosomal rearrangements. The recent sequencing of the zebra finch (Taeniopygia guttata) genome allowed an assessment of the number of intrachromosomal rearrangements between it and the chicken (Gallus gallus) genome, revealing a surprisingly high number of intrachromosomal rearrangements. With the publication of the turkey (Meleagris gallopavo) genome it has become possible to describe intrachromosomal rearrangements between these three important avian species, gain insight into the direction of evolutionary change and assess whether breakpoint regions are reused in birds. To this end, we aligned entire chromosomes between chicken, turkey and zebra finch, identifying syntenic blocks of at least 250 kb. Potential optimal pathways of rearrangements between each of the three genomes were determined, as was a potential Galliform ancestral organization. From this, our data suggest that around one-third of chromosomal breakpoint regions may recur during avian evolution, with 10% of breakpoints apparently recurring in different lineages. This agrees with our previous hypothesis that mechanisms of genome evolution are driven by hotspots of non-allelic homologous recombination.     

Architectural reorganization of the nuclei upon transfer into oocytes accompanies genome reprogramming

The ability of cloned embryos to sustain full-term development depends on the ability of the recipient ooplasm to reprogram the donor cell genome. As the nuclear architecture has recently emerged as a key-factor in the regulation of gene expression, we questioned whether early embryos obtained from transfer of ES metaphasic chromosomes into mouse ooplasm would adopt the somatic or embryonic type of nuclear organization. We have particularly focused on the arrangement of chromosomal territories with respect to the nucleolar compartment, and the pericentric heterochromatin domains called chromocenters. We found that nuclear transfer triggers profound chromatin rearrangements including the dispersion of the donor cell chromocenters components. These rearrangements lead to a typical 1-cell pronuclear organization, namely a radial arrangement of the chromosome territories with centromeres attached to the nucleoli, which adopt the compact fibrillar structure of nucleolar precursor bodies (NPBs). Subsequently, during the second cycle, the cloned embryos undergo further reorganization with the establishment of new chromocenters, clustered in one part of the nucleus, as during normal embryogenesis. We could also establish that the adequate distribution of chromosomal territories at the pronuclear stage seems important for the development until blastocyst.     

Teleost fish with specific genome duplication as unique models of vertebrate evolution

Whole-genome duplication (WGD) is believed to be one of the major evolutionary events that shaped the genome organization of vertebrates. Here, we review recent research on vertebrate genome evolution, specifically on WGD and its consequences for gene and genome evolution in teleost fishes. Recent genome analyses confirmed that all vertebrates experienced two rounds of WGD early in their evolution, and that teleosts experienced a subsequent additional third-round (3R)-WGD. The 3R-WGD was estimated to have occurred 320–400 million years ago in a teleost ancestor, but after its divergence from a common ancestor with living non-teleost actinopterygians (Bichir, Sturgeon, Bowfin, and Gar) based on the analyses of teleost-specific duplicate genes. This 3R-WGD was confirmed by synteny analysis and ancestral karyotype inference using the genome sequences of Tetraodon and medaka. Most of the tetrapods, on the other hand, have not experienced an additional WGD; however, they have experienced repeated chromosomal rearrangements throughout the whole genome. Therefore, different types of chromosomal events have characterized the genomes of teleosts and tetrapods, respectively. The 3R-WGD is useful to investigate the consequences of WGD because it is an evolutionarily recent WGD and thus teleost genomes retain many more WGD-derived duplicates and “traces” of their evolution. In addition, the remarkable morphological, physiological, and ecological diversity of teleosts may facilitate understanding of macrophenotypic evolution on the basis of genetic/genomic information. We highlight the teleosts with 3R-WGD as unique models for future studies on ecology and evolution taking advantage of emerging genomics technologies and systems biology environments.     

Chromosome instability in neoplasia: chaotic roots to continuous growth

Multiple rearrangements of chromosome number and structure are common manifestations of genomic instability encountered in mammalian tumors. In neoplasia, in continuous immortalized growth in vitro, and in animal models, the accumulation of various defects on DNA repair and telomere maintenance machineries, mitotic spindle abnormalities, and breakage-fusion-bridge cycles, deteriorate the precise mitotic distribution of the genomic content, thus producing various types of chromosomal anomalies. These lesions generate tremendous genomic imbalances, which are evolutionary selected, since they force the function of the whole genome towards continuous growth. For more than a century chromosomal rearrangements and aneuploidy in neoplasia have been discussed and a vast number of genes and pathways, directly or indirectly implicated, have been described. In this review, we focus on the biological mechanisms that generate numerical or structural deviations of the normal diploid chromosomal constitution in epithelial neoplasia. There is growing evidence that chromosomal instability is both an epiphenomenon and a leading cause of cancer. We will discuss the roles of genes, chromosome structure, and telomere dysfunction in the initiation of chromosomal instability. We will explore research strategies that can be applied to identify rates of chromosomal instability in a specimen, and the putative biological consequences of karyotypic heterogeneity. Finally, we will re-examine the longstanding hypothesis of the generation of aneuploidy in the context of telomere dysfunction and restoration.     

水稻和其他禾本科植物基因组多倍体起源的证据

基因加倍(Gene duplication)被认为是进化的加速器。古老的基因组加倍事件已经在多个物种中被确定,包括酵母、脊椎动物以及拟南芥等。本研究发现水稻基因组同样存在全基因组加倍事件,大概发生在禾谷类作物分化之前,距今约7000万年。在水稻基因组中,共找到117个加倍区段(Duplicated block),分布在水稻的全部12条染色体,覆盖约60％的水稻基因组。在加倍区段,大约有20％的基因保留了加倍后的姊妹基因对(Duplicated pairs)。与此形成鲜明对照的是加倍区段的转录因子保留了60％的姊妹基因。禾本科植物全基因组加倍事件的确定对研究禾本科植物基因组的进化具有重要影响,暗示了多倍体化及随后的基因丢失、染色体重排等在禾谷类物种分化中扮演了重要角色。     

A Discrete Transition Zone Organizes the Topological and Regulatory Autonomy of the Adjacent Tfap2c and Bmp7 Genes

Despite the well-documented role of remote enhancers in controlling developmental gene expression, the mechanisms that allocate enhancers to genes are poorly characterized. Here, we investigate the cis-regulatory organization of the locus containing the Tfap2c and Bmp7 genes in vivo, using a series of engineered chromosomal rearrangements. While these genes lie adjacent to one another, we demonstrate that they are independently regulated by distinct sets of enhancers, which in turn define non-overlapping regulatory domains. Chromosome conformation capture experiments reveal a corresponding partition of the locus in two distinct structural entities, demarcated by a discrete transition zone. The impact of engineered chromosomal rearrangements on the topology of the locus and the resultant gene expression changes indicate that this transition zone functionally organizes the structural partition of the locus, thereby defining enhancer-target gene allocation. This partition is, however, not absolute: we show that it allows competing interactions across it that may be non-productive for the competing gene, but modulate expression of the competed one. Altogether, these data highlight the prime role of the topological organization of the genome in long-distance regulation of gene expression.     

Tests for gene clustering.

Comparing chromosomal gene order in two or more related species is an important approach to studying the forces that guide genome organization and evolution. Linked clusters of similar genes found in related genomes are often used to support arguments of evolutionary relatedness or functional selection. However, as the gene order and the gene complement of sister genomes diverge progressively due to large scale rearrangements, horizontal gene transfer, gene duplication and gene loss, it becomes increasingly difficult to determine whether observed similarities in local genomic structure are indeed remnants of common ancestral gene order, or are merely coincidences. A rigorous comparative genomics requires principled methods for distinguishing chance commonalities, within or between genomes, from genuine historical or functional relationships. In this paper, we construct tests for significant groupings against null hypotheses of random gene order, taking incomplete clusters, multiple genomes, and gene families into account. We consider both the significance of individual clusters of prespecified genes and the overall degree of clustering in whole genomes.