589 research outputs found
A Computational Method for the Rate Estimation of Evolutionary Transpositions
Genome rearrangements are evolutionary events that shuffle genomic
architectures. Most frequent genome rearrangements are reversals,
translocations, fusions, and fissions. While there are some more complex genome
rearrangements such as transpositions, they are rarely observed and believed to
constitute only a small fraction of genome rearrangements happening in the
course of evolution. The analysis of transpositions is further obfuscated by
intractability of the underlying computational problems.
We propose a computational method for estimating the rate of transpositions
in evolutionary scenarios between genomes. We applied our method to a set of
mammalian genomes and estimated the transpositions rate in mammalian evolution
to be around 0.26.Comment: Proceedings of the 3rd International Work-Conference on
Bioinformatics and Biomedical Engineering (IWBBIO), 2015. (to appear
Genomic distance under gene substitutions
Dias Vieira Braga M, Machado R, Ribeiro LC, Stoye J. Genomic distance under gene substitutions. BMC Bioinformatics. 2011;12(Suppl 9: Proc. of RECOMB-CG 2011): S8.Background:
The distance between two genomes is often computed by comparing only the common markers between them. Some approaches are also able to deal with non-common markers, allowing the insertion or the deletion of such markers. In these models, a deletion and a subsequent insertion that occur at the same position of the genome count for two sorting steps.
Results:
Here we propose a new model that sorts non-common markers with substitutions, which are more powerful operations that comprehend insertions and deletions. A deletion and an insertion that occur at the same position of the genome can be modeled as a substitution, counting for a single sorting step.
Conclusions:
Comparing genomes with unequal content, but without duplicated markers, we give a linear time algorithm to compute the genomic distance considering substitutions and double-cut-and-join (DCJ) operations. This model provides a parsimonious genomic distance to handle genomes free of duplicated markers, that is in practice a lower bound to the real genomic distances. The method could also be used to refine orthology assignments, since in some cases a substitution could actually correspond to an unannotated orthology
A Unifying Model of Genome Evolution Under Parsimony
We present a data structure called a history graph that offers a practical
basis for the analysis of genome evolution. It conceptually simplifies the
study of parsimonious evolutionary histories by representing both substitutions
and double cut and join (DCJ) rearrangements in the presence of duplications.
The problem of constructing parsimonious history graphs thus subsumes related
maximum parsimony problems in the fields of phylogenetic reconstruction and
genome rearrangement. We show that tractable functions can be used to define
upper and lower bounds on the minimum number of substitutions and DCJ
rearrangements needed to explain any history graph. These bounds become tight
for a special type of unambiguous history graph called an ancestral variation
graph (AVG), which constrains in its combinatorial structure the number of
operations required. We finally demonstrate that for a given history graph ,
a finite set of AVGs describe all parsimonious interpretations of , and this
set can be explored with a few sampling moves.Comment: 52 pages, 24 figure
On pairwise distances and median score of three genomes under DCJ
In comparative genomics, the rearrangement distance between two genomes
(equal the minimal number of genome rearrangements required to transform them
into a single genome) is often used for measuring their evolutionary
remoteness. Generalization of this measure to three genomes is known as the
median score (while a resulting genome is called median genome). In contrast to
the rearrangement distance between two genomes which can be computed in linear
time, computing the median score for three genomes is NP-hard. This inspires a
quest for simpler and faster approximations for the median score, the most
natural of which appears to be the halved sum of pairwise distances which in
fact represents a lower bound for the median score.
In this work, we study relationship and interplay of pairwise distances
between three genomes and their median score under the model of
Double-Cut-and-Join (DCJ) rearrangements. Most remarkably we show that while a
rearrangement may change the sum of pairwise distances by at most 2 (and thus
change the lower bound by at most 1), even the most "powerful" rearrangements
in this respect that increase the lower bound by 1 (by moving one genome
farther away from each of the other two genomes), which we call strong, do not
necessarily affect the median score. This observation implies that the two
measures are not as well-correlated as one's intuition may suggest.
We further prove that the median score attains the lower bound exactly on the
triples of genomes that can be obtained from a single genome with strong
rearrangements. While the sum of pairwise distances with the factor 2/3
represents an upper bound for the median score, its tightness remains unclear.
Nonetheless, we show that the difference of the median score and its lower
bound is not bounded by a constant.Comment: Proceedings of the 10-th Annual RECOMB Satellite Workshop on
Comparative Genomics (RECOMB-CG), 2012. (to appear
Parking functions, labeled trees and DCJ sorting scenarios
In genome rearrangement theory, one of the elusive questions raised in recent
years is the enumeration of rearrangement scenarios between two genomes. This
problem is related to the uniform generation of rearrangement scenarios, and
the derivation of tests of statistical significance of the properties of these
scenarios. Here we give an exact formula for the number of double-cut-and-join
(DCJ) rearrangement scenarios of co-tailed genomes. We also construct effective
bijections between the set of scenarios that sort a cycle and well studied
combinatorial objects such as parking functions and labeled trees.Comment: 12 pages, 3 figure
Estimating true evolutionary distances under rearrangements, duplications, and losses
Background: The rapidly increasing availability of whole-genome sequences has enabled the study of whole-genome evolution. Evolutionary mechanisms based on genome rearrangements have attracted much attention and given rise to many models; somewhat independently, the mechanisms of gene duplication and loss have seen much work. However, the two are not independent and thus require a unified treatment, which remains missing to date. Moreover, existing rearrangement models do not fit the dichotomy between most prokaryotic genomes (one circular chromosome) and most eukaryotic genomes (multiple linear chromosomes). Results: To handle rearrangements, gene duplications and losses, we propose a new evolutionary model and the corresponding method for estimating true evolutionary distance. Our model, inspired from the DCJ model, is simple and the first to respect the prokaryotic/eukaryotic structural dichotomy. Experimental results on a wide variety of genome structures demonstrate the very high accuracy and robustness of our distance estimator. Conclusions: We give the first robust, statistically based, estimate of genomic pairwise distances based on rearrangements, duplications and losses, under a model that respects the structural dichotomy between prokaryotic and eukaryotic genomes. Accurate and robust estimates in true evolutionary distances should translate into much better phylogenetic reconstructions as well as more accurate genomic alignments, while our new model of genome rearrangements provides another refinement in simplicity and verisimilitude
The transcription factor NFATc2 controls IL-6-dependent T cell activation in experimental colitis.
The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell-dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-6, rather than IL-23 and -17, are essential for oxazolone colitis induction. Administration of hyper-IL-6 blocked the protective effects of NFATc2 deficiency in experimental colitis, suggesting that IL-6 signal transduction plays a major pathogenic role in vivo. Finally, adoptive transfer of IL-6 and wild-type T cells demonstrated that oxazolone colitis is critically dependent on IL-6 production by T cells. Collectively, these results define a unique regulatory role for NFATc2 in colitis by controlling mucosal T cell activation in an IL-6-dependent manner. NFATc2 in T cells thus emerges as a potentially new therapeutic target for inflammatory bowel diseases
Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia
Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells
- …