74 research outputs found
Limited Lifespan of Fragile Regions in Mammalian Evolution
An important question in genome evolution is whether there exist fragile
regions (rearrangement hotspots) where chromosomal rearrangements are happening
over and over again. Although nearly all recent studies supported the existence
of fragile regions in mammalian genomes, the most comprehensive phylogenomic
study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some
doubts about their existence. We demonstrate that fragile regions are subject
to a "birth and death" process, implying that fragility has limited
evolutionary lifespan. This finding implies that fragile regions migrate to
different locations in different mammals, explaining why there exist only a few
chromosomal breakpoints shared between different lineages. The birth and death
of fragile regions phenomenon reinforces the hypothesis that rearrangements are
promoted by matching segmental duplications and suggests putative locations of
the currently active fragile regions in the human genome
On Nonperturbative Calculations in Quantum Electrodynamics
A new approach to nonperturbative calculations in quantum electrodynamics is
proposed. The approach is based on a regular iteration scheme for solution of
Schwinger-Dyson equations for generating functional of Green functions. The
approach allows one to take into account the gauge invariance conditions (Ward
identities) and to perform the renormalization program. The iteration scheme
can be realized in two versions. The first one ("perturbative vacuum")
corresponds to chain summation in the diagram language. In this version in
four-dimensional theory the non-physical singularity (Landau pole) arises which
leads to the triviality of the renormalized theory. The second version
("nonperturbative vacuum") corresponds to ladder summation and permits one to
make non-perturbative calculations of physical quantities in spite of the
triviality problem. For chiral-symmetrical leading approximation two terms of
the expansion of the first-step vertex function over photon momentum are
calculated. A formula for anomalous magnetic moment is obtained. A problem of
dynamical chiral symmetry breaking (DCSB) is considered, the calculations are
performed for renormalized theory in Minkowsky space. In the strong coupling
region DCSB-solutions arise. For the renormalized theory a DCSB-solution is
also possible in the weak coupling region but with a subsidiary condition on
the value of .Comment: 31 pages, Plain LaTex, no figures. Journal version: some discussion
and refs. are adde
Efficient algorithms for analyzing segmental duplications with deletions and inversions in genomes
Background: Segmental duplications, or low-copy repeats, are common in mammalian genomes. In the human genome, most segmental duplications are mosaics comprised of multiple duplicated fragments. This complex genomic organization complicates analysis of the evolutionary history of these sequences. One model proposed to explain this mosaic patterns is a model of repeated aggregation and subsequent duplication of genomic sequences. Results: We describe a polynomial-time exact algorithm to compute duplication distance, a genomic distance defined as the most parsimonious way to build a target string by repeatedly copying substrings of a fixed source string. This distance models the process of repeated aggregation and duplication. We also describe extensions of this distance to include certain types of substring deletions and inversions. Finally, we provide an description of a sequence of duplication events as a context-free grammar (CFG). Conclusion: These new genomic distances will permit more biologically realistic analyses of segmental duplications in genomes.
progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement
Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence.The multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve
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