Autosomal similarity revealed by eukaryotic genomic comparison.
ABSTRACT: To describe eukaryotic autosomes quantitatively and determine differences between them in terms of amino acid sequences of genes, functional classification of proteins, and complete DNA sequences, we applied two theoretical methods, the Proteome-vector method and the function of degree of disagreement (FDOD) method, that are based on function and sequence similarity respectively, to autosomes from nine eukaryotes. No matter what aspect of the autosome is considered, the autosomal differences within each organism were less than that between species. Our results show that eukaryotic autosomes resemble each other within a species while those from different organisms differ. We propose a hypothesis (named intra-species autosomal random shuffling) as an explanation for our results and suggest that lateral gene transfer (LGT) did not occur frequently during the evolution of eukarya.
Project description:When species interbreed, the hybrid offspring that are produced are often sterile. If only one hybrid sex is sterile, it is almost always the heterogametic (XY or ZW) sex. Taking this trend into account, the predominant model used to explain the genetic basis of F1 sterility involves a deleterious interaction between recessive sex-linked loci from one species and dominant autosomal loci from the other species. This model is difficult to evaluate, however, as only a handful of loci influencing interspecies hybrid sterility have been identified, and their autosomal genetic interactors have remained elusive. One hindrance to their identification has been the overwhelming effect of the sex chromosome in mapping studies, which could 'mask' the ability to accurately map autosomal factors. Here, we use a novel approach employing attached-X chromosomes to create reciprocal backcross interspecies hybrid males that have a non-recombinant sex chromosome and recombinant autosomes. The heritable variation in phenotype is thus solely caused by differences in the autosomes, thereby allowing us to accurately identify the number and location of autosomal sterility loci. In one direction of backcross, all males were sterile, indicating that sterility could be entirely induced by the sex chromosome complement in these males. In the other direction, we identified nine quantitative trait loci that account for a surprisingly large amount (56%) of the autosome-induced phenotypic variance in sterility, with a large contribution of autosome-autosome epistatic interactions. These loci are capable of acting dominantly, and thus could contribute to F1 hybrid sterility.
Project description:With the daily release of data from whole genome sequencing projects, tools to facilitate comparative studies are hard-pressed to keep pace. Graphical software solutions can readily recognize synteny by measuring similarities between sequences. Nevertheless, regions of dissimilarity can prove to be equally informative; these regions may harbor genes acquired via lateral gene transfer (LGT), signify gene loss or gain, or include coding regions under strong selection. Previously, we developed the software S-plot. This tool employed an alignment-free approach for comparing bacterial genomes and generated a heatmap representing the genomes' similarities and dissimilarities in nucleotide usage. In prior studies, this tool proved valuable in identifying genome rearrangements as well as exogenous sequences acquired via LGT in several bacterial species. Herein, we present the next generation of this tool, S-plot2. Similar to its predecessor, S-plot2 creates an interactive, 2-dimensional heatmap capturing the similarities and dissimilarities in nucleotide usage between genomic sequences (partial or complete). This new version, however, includes additional metrics for analysis, new reporting options, and integrated BLAST query functionality for the user to interrogate regions of interest. Furthermore, S-plot2 can evaluate larger sequences, including whole eukaryotic chromosomes. To illustrate some of the applications of the tool, 2 case studies are presented. The first examines strain-specific variation across the <i>Pseudomonas aeruginosa</i> genome and strain-specific LGT events. In the second case study, corresponding human, chimpanzee, and rhesus macaque autosomes were studied and lineage specific contributions to divergence were estimated. S-plot2 provides a means to both visually and quantitatively compare nucleotide sequences, from microbial genomes to eukaryotic chromosomes. The case studies presented illustrate just 2 potential applications of the tool, highlighting its capability to identify and investigate the variation in molecular divergence rates across sequences. S-plot2 is freely available through https://bitbucket.org/lkalesinskas/splot and is supported on the Linux and MS Windows operating systems.
Project description:Rumex hastatulus is the North American endemic dioecious plant with heteromorphic sex chromosomes. It is differentiated into two chromosomal races: Texas (T) race characterised by a simple XX/XY sex chromosome system and North Carolina (NC) race with a polymorphic XX/XY1Y2 sex chromosome system. The gross karyotype morphology in NC race resembles the derived type, but chromosomal changes that occurred during its evolution are poorly understood. Our C-banding/DAPI and fluorescence in situ hybridization (FISH) experiments demonstrated that Y chromosomes of both races are enriched in DAPI-positive sequences and that the emergence of polymorphic sex chromosome system was accompanied by the break of ancestral Y chromosome and switch in the localization of 5S rDNA, from autosomes to sex chromosomes (X and Y2). Two contrasting domains were detected within North Carolina Y chromosomes: the older, highly heterochromatinised, inherited from the original Y chromosome and the younger, euchromatic, representing translocated autosomal material. The flow-cytometric DNA estimation showed ∼3.5 % genome downsizing in the North Carolina race. Our results are in contradiction to earlier reports on the lack of heterochromatin within Y chromosomes of this species and enable unambiguous identification of autosomes involved in the autosome-heterosome translocation, providing useful chromosome landmarks for further studies on the karyotype and sex chromosome differentiation in this species.
Project description:BACKGROUND: Sequencing of the genomes of several Drosophila allows for the first precise analyses of how global sequence patterns change among multiple, closely related animal species. A basic question is whether there are characteristic features that differentiate chromosomes within a species or between different species. RESULTS: We explored the euchromatin of the chromosomes of seven Drosophila species to establish their global patterns of DNA sequence diversity. Between species, differences in the types and amounts of simple sequence repeats were found. Within each species, the autosomes have almost identical oligonucleotide profiles. However, X chromosomes and autosomes have, in all species, a qualitatively different composition. The X chromosomes are less complex than the autosomes, containing both a higher amount of simple DNA sequences and, in several cases, chromosome-specific repetitive sequences. Moreover, we show that the right arm of the X chromosome of Drosophila pseudoobscura, which evolved from an autosome 10 - 18 millions of years ago, has a composition which is identical to that of the original, left arm of the X chromosome. CONCLUSION: The consistent differences among species, differences among X chromosomes and autosomes and the convergent evolution of X and neo-X chromosomes demonstrate that strong forces are acting on drosophilid genomes to generate peculiar chromosomal landscapes. We discuss the relationships of the patterns observed with differential recombination and mutation rates and with the process of dosage compensation.
Project description:BACKGROUND:Chromosome counting is a process in which cells determine somehow their intrinsic chromosome number(s). The best-studied cellular mechanism that involves chromosome counting is 'chromosome-kissing' and X-chromosome inactivation (XCI) mechanism. It is necessary for the well-known dosage compensation between the genders in mammals to balance the number of active X-chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI, two X-chromosomes are coming in close proximity and pair physically by a specific segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene. RESULTS:An Ensembl BLAST search for human and mouse SLC16A2/Slc16a2 homologues revealed, that highly similar sequences can be found at almost each chromosome in the corresponding genomes. Additionally, a BLAST search for SLC16A2/TSIX/XIST (genes responsible for XCI) reveled that "SLC16A2/TSIX/XIST like sequences" cover equally all chromosomes, too. With respect to this we provide following hypotheses. HYPOTHESES:If a single genomic region containing the SLC16A2 gene on X-chromosome is responsible for maintaining "balanced" active copy numbers, it is possible that similar sequences or gene/s have the same function on other chromosomes (autosomes). SLC16A2 like sequences on autosomes could encompass evolutionary older, but functionally active key regions for chromosome counting in early embryogenesis. Also SLC16A2 like sequence on autosomes could be involved in inappropriate chromosomes pairing and, thereby be involved in aneuploidy formation during embryogenesis and cancer development. Also, "SLC16A2/TSIX/XIST gene like sequence combinations" covering the whole genome, could be important for the determination of X:autosome ratio in cells and chromosome counting. CONCLUSIONS:SLC16A2 and/or SLC16A2/TSIX/XIST like sequence dispersed across autosomes and X-chromosome(s) could serve as bases for a counting mechanism to determine X:autosome ratio and could potentially be a mechanism by which a cell also counts its autosomes. It could also be that such specific genomic regions have the same function for each specific autosome. As errors during the obviously existing process of chromosome counting are one if not the major origin of germline/somatic aneuploidy the here presented hypotheses should further elaborated and experimentally tested.
Project description:Carriers of balanced constitutional reciprocal translocations usually present a normal phenotype, but often show reproductive disorders. For the first time in pigs, we analyzed the meiotic process of an autosome-autosome translocation associated with azoospermia. Meiotic process analysis revealed the presence of unpaired autosomal segments with histone γH2AX accumulation sometimes associated with the XY body. Additionally, γH2AX signals were observed on apparently synapsed autosomes other than the SSC1 or SSC15, as previously observed in Ataxia with oculomotor apraxia type 2 patients or knock-out mice for the Senataxin gene. Gene expression showed a downregulation of genes selected on chromosomes 1 and 15, but no upregulation of SSCX genes. We hypothesized that the total meiotic arrest observed in this boar might be due to the silencing of crucial autosomal genes by the mechanism referred to as meiotic silencing of unsynapsed chromatin (MSUC).
Project description:Sex chromosomes are generally morphologically and functionally distinct, but the evolutionary forces that cause this differentiation are poorly understood. Drosophila americana americana was used in this study to examine one aspect of sex chromosome evolution, the degeneration of nonrecombining Y chromosomes. The primary X chromosome of D. a. americana is fused with a chromosomal element that was ancestrally an autosome, causing this homologous chromosomal pair to segregate with the sex chromosomes. Sequence variation at the Alcohol Dehydrogenase (Adh) gene was used to determine the pattern of nucleotide variation on the neo-sex chromosomes in natural populations. Sequences of Adh were obtained for neo-X and neo-Y chromosomes of D. a. americana, and for Adh of D. a. texana, in which it is autosomal. No significant sequence differentiation is present between the neo-X and neo-Y chromosomes of D. a. americana or the autosomes of D. a. texana. There is a significantly lower level of sequence diversity on the neo-Y chromosome relative to the neo-X in D. a. americana. This reduction in variability on the neo-Y does not appear to have resulted from a selective sweep. Coalescent simulations of the evolutionary transition of an autosome into a Y chromosome indicate there may be a low level of recombination between the neo-X and neo-Y alleles of Adh and that the effective population size of this chromosome may have been reduced below the expected value of 25% of the autosomal effective size, possibly because of the effects of background selection or sexual selection.
Project description:Analyses of genomic diversity along the X chromosome and of its correlation with autosomal diversity can facilitate understanding of evolutionary forces in shaping sex-linked genomic architecture. Strong selective sweeps and accelerated genetic drift on the X-chromosome have been inferred in primates and other model species, but no such insight has yet been gained in domestic animals compared with their wild relatives. Here, we analyzed X-chromosome variability in a large ovine data set, including a BeadChip array for 943 ewes from the world's sheep populations and 110 whole genomes of wild and domestic sheep. Analyzing whole-genome sequences, we observed a substantially reduced X-to-autosome diversity ratio (∼0.6) compared with the value expected under a neutral model (0.75). In particular, one large X-linked segment (43.05-79.25 Mb) was found to show extremely low diversity, most likely due to a high density of coding genes, featuring highly conserved regions. In general, we observed higher nucleotide diversity on the autosomes, but a flat diversity gradient in X-linked segments, as a function of increasing distance from the nearest genes, leading to a decreased X: autosome (X/A) diversity ratio and contrasting to the positive correlation detected in primates and other model animals. Our evidence suggests that accelerated genetic drift but reduced directional selection on X chromosome, as well as sex-biased demographic events, explain low X-chromosome diversity in sheep species. The distinct patterns of X-linked and X/A diversity we observed between Middle Eastern and non-Middle Eastern sheep populations can be explained by multiple migrations, selection, and admixture during the domestic sheep's recent postdomestication demographic expansion, coupled with natural selection for adaptation to new environments. In addition, we identify important novel genes involved in abnormal behavioral phenotypes, metabolism, and immunity, under selection on the sheep X-chromosome.
Project description:The formation of new genes is a primary driving force of evolution in all organisms. The de novo evolution of new genes from non-protein-coding genomic regions is emerging as an important additional mechanism for novel gene creation. Y chromosomes underlie sex determination in mammals and contain genes that are required for male-specific functions. In this study, a search was undertaken for Y chromosome de novo genes derived from non-protein-coding sequences. The Y chromosome orphan gene variable charge, Y-linked (VCY)2, is an autosome-derived gene that has sequence similarity to large autosomal fragments but lacks an autosomal protein-coding homolog. VCY2 locates in the amplicon containing long DNA fragments that were transposed from autosomes to the Y chromosome before the ape-monkey split. We confirmed that VCY2 cannot be encoded by autosomes due to the presence of multiple disablers that disrupt the open reading frame, such as the absence of start or stop codons and the presence of premature stop codons. Similar observations have been made for homologs in the autosomes of the chimpanzee, gorilla, rhesus macaque, baboon and out-group marmoset, which suggests that there was a non-protein-coding ancestral VCY2 that was common to apes and monkeys that predated the transposition event. Furthermore, while protein-coding orthologs are absent, a putative non-protein-coding VCY2 with conserved disablers was identified in the rhesus macaque Y chromosome male-specific region. This finding implies that VCY2 might have not acquired its protein-coding ability before the ape-monkey split. VCY2 encodes a testis-specific expressed protein and is involved in the pathologic process of male infertility, and the acquisition of this gene might improve male fertility. This is the first evidence that de novo genes can be generated from transposed autosomal non-protein-coding segments, and this evidence provides novel insights into the evolutionary history of the Y chromosome.
Project description:Genomic analyses of Drosophila species suggest that the X chromosome presents an unfavourable environment for the expression of genes in the male germline. A previous study in D. melanogaster used a reporter gene driven by a testis-specific promoter to show that expression was greatly reduced when the gene was inserted onto the X chromosome as compared with the autosomes. However, a limitation of this study was that only the expression regulated by a single, autosomal-derived promoter was investigated. To test for an increase in expression associated with 'escaping' the X chromosome, we analysed reporter gene expression driven by the promoters of three X-linked, testis-expressed genes (CG10920, CG12681 and CG1314) that were inserted randomly throughout the D. melanogaster genome. In all cases, insertions on the autosomes showed significantly higher expression than those on the X chromosome. Thus, even genes whose regulation has adapted to the X-chromosomal environment show increased male germline expression when relocated to an autosome. Our results provide direct experimental evidence for the suppression of X-linked gene expression in the Drosophila male germline that is independent of gene dose.