Domain rearrangements in protein evolution

Most eukaryotic proteins are multi-domain proteins that are created from fusions of genes, deletions and internal repetitions. An investigation of such evolutionary events requires a method to find the domain architecture from which each protein originates. Therefore, we defined a novel measure, domain distance, which is calculated as the number of domains that differ between two domain architectures. Using this measure the evolutionary events that distinguish a protein from its closest ancestor have been studied and it was found that indels are more common than internal repetition and that the exchange of a domain is rare. Indels and repetitions are common at both the N and C-terminals while they are rare between domains. The evolution of the majority of multi-domain proteins can be explained by the stepwise insertions of single domains, with the exception of repeats that sometimes are duplicated several domains in tandem. We show that domain distances agree with sequence similarity and semantic similarity based on gene ontology annotations. In addition, we demonstrate the use of the domain distance measure to build evolutionary trees. Finally, the evolution of multi-domain proteins is exemplified by a closer study of the evolution of two protein families, non-receptor tyrosine kinases and RhoGEFs.     

Chromosome rearrangements in canine fibrosarcomas

We have previously reported the use of six- and seven-color paint sets in the analysis of canine soft tissue sarcomas. Here we combine this technique with flow sorting of translocation chromosomes, reverse painting, and polymerase chain reaction (PCR) analysis of the gene content of the reverse paint in order to provide a more detailed analysis of cytogenetic abnormalities in canine tumors. We examine two fibrosarcomas, both from female Labrador retrievers, and show abnormalities in chromosomes 11 and 30 in both cases. Evidence of involvement of TGFBR1 is presented for one tumor.     

Mitochondrial genomic rearrangements in songbirds

The organization of the mitochondrial genome is generally very conserved among vertebrates. Because of this, examination of the rare rearrangements which do occur has been suggested as offering a powerful alternative to phylogenetic analyses of mitochondrial DNA sequences. Here, we report on an avian mitochondrial rearrangement in a group of oscine passerines (warblers of the genus Phylloscopus). This rearrangement is identical to the mitochondrial organization recently identified in representatives of four orders of birds, including subsoscine Passeriformes. The rearrangement involves the movement of three genes (tRNA(Pro), NADH6, and tRNA(Glu)) from their normal position in birds between tRNA(Thr) and the control region (CR), to a new location between the CR and a novel, supposedly noncoding (NC), region. Our results suggest that this derived arrangement cannot be used to distinguish between suboscine and oscine passerines, as it has multiple origins both within Passeriformes and within birds as a whole. We found short stretches of DNA with high degrees of similarity between the CR and each NC region, respectively, all of which could be located in the same area of the CR. This suggests that the CR and the NC region are homologous and that the mechanism behind this mitochondrial rearrangement is a tandem duplication followed by multiple deletions. However, the similarities between the control and NC regions of each species were less pronounced than those between the control or NC regions from the different species, supporting the hypothesis of a single basal rearrangement in the Phylloscopus warblers.     

Engineering chromosomal rearrangements in mice

The combination of gene-targeting techniques in mouse embryonic stem cells and the Cre/loxP site-specific recombination system has resulted in the emergence of chromosomal-engineering technology in mice. This advance has opened up new opportunities for modelling human diseases that are associated with chromosomal rearrangements. It has also led to the generation of visibly marked deletions and balancer chromosomes in mice, which provide essential reagents for maximizing the efficiency of large-scale mutagenesis efforts and which will accelerate the functional annotation of mammalian genomes, including the human genome.     

Chromosome rearrangements in Giardia lamblia

Recent studies have shown that the genome of Giardia lamblia is plastic. Clinical isolates exhibit extensive karyotypic heterogeneity and chromosome rearrangements occur frequently, in vitro. In this review, Sylvie Le Blancq looks at genome organization and the impact of DNA rearrangement events.     

Complex chromosomal rearrangements

Complex Chromosomal Rearrangements (CCRs) are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. CCRs preferentially occur during spermatogenesis and are transmitted in families through oogenesis. Recent investigation showed that CCRs are more complex and more common than initially appreciated. Here 1 present an overview of CCRs, including the important impact of CCRs in fertility, the mechanism of their development, the various meiotic errors that can occur and their consequences. The review also discusses the differential transmission of CCRs in males and females, the incidence of pregnancy outcomes of CCR carriers, genetic counseling and prenatal diagnosis.     

Recombination-mediated genome rearrangements

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Spontaneous rearrangements in RNA sequences.

The ability of RNAs to spontaneously rearrange their sequences under physiological conditions is demonstrated using the molecular colony technique, which allows single RNA molecules to be detected provided that they are amplifiable by the replicase of bacteriophage Qbeta. The rearrangements are Mg2+-dependent, sequence-non-specific, and occur both in trans and in cis at a rate of 10(-9) h(-1) per site. The results suggest that the mechanism of spontaneous RNA rearrangements differs from the transesterification reactions earlier observed in the presence of Qbeta replicase, and have a number of biologically important implications.     

Structural rearrangements in soluble mitochondrial ATPase

Treatment of isolated factor F1 by 1% dimethylsuberimidate in the presence of 50 mM (NH4)2SO4 leads to the formation of four different types of cross-linked dimers of the subunits, on average one dimer per molecule of the enzyme. This treatment results in 60-70% inactivation of factor F1. Factor F1 treated with dimethylsuberimidate does not show a change in the sedimentation coefficient and is not inactivated in the cold; it is not inactivated in the presence of Mg2+ either, nor is it activated by anions. Incubation of the cross-linked factor F1 with ADP does not lead to inactivation, although the ability to tightly bind ADP is retained. The total quantity of tightly bound ADP reaches 5 mol per mol of the cross-linked factor F1. Cross-linking of factor F1 also prevents the slow inactivation of the enzyme coupled with the hydrolysis of Mg-ATP and Mg-GTP. The dependence of the inactivation rate constant on the concentration of Mg-ATP and Mg-GTP at substrate concentrations of 0.05-2 mM is characterized by the same values of Km,app as those of the ATPase and GTPase activities of factor F1. The probability of the inactivation of factor F1 per turnover remains constant for all the concentrations of the substrates studied and is 2 . 10(-6) per turnover for the ATPase reaction and 2 . 10(-5) per turnover for the GTPase reaction. Moderate hydrostatic pressure (up to 150 atmospheres) greatly accelerates ATP-induced inactivation of factor F1. The activation volume (delta V*) of the inactivation process is equal to 5.1 . 10(-4) cm3/g, which is evidence of considerable changes in the extent of protein hydration during inactivation. Inactivation of the enzyme under pressure is accompanied by dissociation into subunits. Dimethyladipimidate, which does not cause intersubunit cross-linking in the molecule of factor F1, does not alter the properties of the native enzyme. It is suggested that the formation of one intersubunit cross-link in the molecule of factor F1 by dimethylsuberimidate affects the ability of the enzyme to undergo co-operative rearrangements of the quaternary structure under the influence of Mg2+, ADP, ATP, anions, and low temperature. The rate constants of ATP binding to the active site of factor F2 (k+1) = 2 . 10(8) M-1 . min-1), of ATP release from the active site (k-1 = 2 . 10(-2) min-1), and of ADP and Pi release from the active site (k2 = 5 . 10(3) min-1) have been determined. The results obtained confirm the correctness of Boyer's idea, according to which ATP is formed in the active site of mitochondrial ATPase without any external source of energy. Energy is used at the stage of the release of synthesized ATP from the active site of ATPase in the solution.     

Karyotypic rearrangements in 20 uterine leiomyomas

Short-term cultures from 106 uterine leiomyomas have been cytogenetically investigated. In 29 cases the number of metaphases was insufficient for analysis. A normal female karyotype was found in 57 tumors and clonal chromosome rearrangements in 20. A reciprocal translocation, t(12;14) (q14----q15;q23----q24), was observed in 10 tumors and probably represents a primary change of tumorigenic importance. In four of the tumors containing this specific anomaly, secondary chromosome changes were also present. The 10 karyotypically abnormal leiomyomas without a t(12;14) had various structural and numerical aberrations involving chromosomes 1, 2, 3, 4, 6, 8, 9, 10, 11, 12, 13, and 19. Different structural changes of chromosome 1 were the second most frequent abnormalities, being found in five tumors. Ring chromosomes were observed in three cases, but never as the sole change.     

Chromosomal rearrangements and speciation

Several authors have proposed that speciation frequently occurs when a population becomes fixed for one or more chromosomal rearrangements that reduce fitness when they are heterozygous. This hypothesis has little theoretical support because mutations that cause a large reduction in fitness can be fixed through drift only in small, inbred populations. Moreover, the effects of chromosomal rearrangements on fitness are unpredictable and vary significantly between plants and animals. I argue that rearrangements reduce gene flow more by suppressing recombination and extending the effects of linked isolation genes than by reducing fitness. This unorthodox perspective has significant implications for speciation models and for the outcomes of contact between neospecies and their progenitor(s).