An Improved Genetic Algorithm for Problem of Genome Rearrangement

In view of the fact that the problem of sorting unsigned permutation by reversal is NP-hard, while the problem of sorting signed permutation by reversal can be solved easily, in this paper, we first transform an unsigned permutation of length n,π （π1 ,… ,πn）, into a set S（π） containing 2^n signed permutations, so that the reversal distance of π is equal to the reversal distance of the optimal signed permutation in S（π）. Then analyze the structural features of S（π） by creating a directed graph and induce a new computing model of this question. Finally, an improved genetic algorithm for solving the new model is proposed. Experimental results show that the proposed model and algorithm is very efficient in practice.

From germline genome to highly fragmented somatic genome:genome-wide DNA rearrangement during the sexual process in ciliated protists

Genomes are incredibly dynamic within diverse eukaryotes and programmed genome rearrangements(PGR)play important roles in generating genomic diversity.However,genomes and chromosomes in metazoans are usually large in size which prevents our understanding of the origin and evolution of PGR.To expand our knowledge of genomic diversity and the evolutionary origin of complex genome rearrangements,we focus on ciliated protists(ciliates).Ciliates are single-celled eukaryotes with highly fragmented somatic chromosomes and massively scrambled germline genomes.PGR in ciliates occurs extensively by removing massive amounts of repetitive and selfish DNA elements found in the silent germline genome dur-ing development of the somatic genome.We report the partial germline genomes of two spirotrich ciliate species,namely Strombidium cf.sulcatum and Halteria grandinella,along with the most compact and highly fragmented somatic genome for S.cf.sulcatum.We provide the first insights into the genome rearrangements of these two species and compare these features with those of other ciliates.Our analyses reveal:(1)DNA sequence loss through evolution and during PGR in S.cf.sulcatum has combined to produce the most compact and efficient nanochromosomes observed to date;(2)the compact,transcriptome-like somatic genome in both species results from extensive removal of a relatively large number of shorter germline-specific DNA sequences;(3)long chromosome breakage site motifs are duplicated and retained in the somatic genome,revealing a complex model of chromosome fragmentation in spirotrichs;(4)gene scrambling and alternative pro-cessing are found throughout the core spirotrichs,offering unique opportunities to increase genetic diversity and regulation in this group.

The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer ＇omics＇, including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

A paradox： rapid evolution rates of germline-limited sequences are associated with conserved patterns of rearrangements in cryptic species of Chilodonella uncinata(Protista, Ciliophora)

Some of the most extreme genome wide rearrangements are found in ciliates, which are unique in possessing both germline micronucleus and somatic macronucleus in every cell/organism. A series of DNA rearrangement events, including DNA elimination, chromosomal fragmentation, gene unscrambling and alternative processing, happen during macronuclear development. To assess the molecular evolution of macronuclear and germline-limited sequences in different cryptic species of Chilodonella uncinata, we characterized the actin, α-tubulin and β-tubulin genes in the micronucleus and macronucleus genomes of USA-SC2 strain and compared them with other strains(i.e. cryptic species). Three main results are:(i) rearrangement patterns between germline and soma are conserved for each gene among the cryptic species of C. uncinata;(ii) in contrast, the germlinelimited regions are highly divergent in sequence and length among the cryptic species;(iii) pointer shifting is frequent among the cryptic species. We speculate that pointer sequences may serve as the buffer between the conserved macronuclear destined sequences and rapidly-evolving internal eliminated sequences. The data combined with previous studies demonstrate the plasticity of gene rearrangement among different groups of ciliates and add to the growing data for the role of genome rearrangements in species differentiation.

Some Algorithmic Challenges in Genome-Wide Ortholog Assignment

Genome-scale assignment of orthologous genes is a fundamental and challenging problem in computational biology and has a wide range of applications in comparative genomics, functional genomics, and systems biology. Many methods based on sequence similarity, phylogenetic analysis, chromosomal syntenic information, and genome rearrangement have been proposed in recent years for ortholog assignment. Although these methods produce results that largely agree with each other, their results may still contain significant differences. In this article, we consider the recently proposed parsimony approach for assigning orthologs between closely related genomes based on genome rearrangement, which essentially attempts to transform one genome into another by the smallest number of genome rearrangement events including reversal, translocation, fusion, and fission, as well as gene duplication events. We will highlight some of the challenging algorithmic problems that arise in the approach including （i） minimum common substring partition, （ii） signed reversal distance with duplicates, and （iii） signed transposition distance with duplicates. The most recent progress towards the solution of these problems will be reviewed and some open questions will he posed. We will also discuss some possible extensions of the approach to the simultaneous comparison of multiple genomes.

Inter-chromosomal insertions into wild-type chromosomes induced by SCRaMbLE

Genomic rearrangements play a crucial role in shaping biological phenotypic diversity and driving species evolution.Synthetic chromosome rearrangement and modification by LoxP-mediated evolution(SCRaMbLE)has been applied to explore large-scale genomic rearrangements,yet it has been observed that these rearrangements occur exclusively in genomic regions containing loxPsym sites.Here,we found that SCRaMbLE of synthetic yeast harboring synthetic chromosome V and X can generate a variety of synthetic segment insertions into wild-type chromosomes,ranging from 1 to 300 kb.Furthermore,it was revealed that the novel insertions impacted the transcriptional level of neighboring regions and affected the production of exemplar pathway of zeaxanthin.Collectively,our results improve the understanding of the ability of SCRaMbLE to generate complex structural variations in nonsynthetic regions and provide a potential model to explore genomic transposable events.

Genomic Rearrangement in Endogenous Long Terminal Repeat Retrotransposons of Rice Lines Introgressed by Wild Rice （Zizania latifolia Griseb.）

Stochastic introgression of alien DNA may impose a genomic stress to the recipient genome. Herein, we report that apparent de novo genomic rearrangements in 10 of 13 selected endogenous, lowcopy, and potentially active long terminal repeat （LTR） retrotransposons occurred in one or more of three rice lines studied that were introgressed by wild rice （Zizania latifolia Griseb.）. For nine retrotransposons in which both the reverse-transcriptase （RT） region and the LTR region were available, largely concordant rearrangements occurred at both regions in five elements and at the RT region only in the remaining four elements. A marked proportion of the genomic changes was shared by two or all three introgression lines that were derived from a single F~ plant. This indicates that most of the genomic changes occurred at early developmental stages of the F~ somatic cells, which then gave rise to germline cells, and, hence, ensured inheritance of the changes to later generations. Possible causes and potential implications of the introgression-induced genomic rearrangements in LTR retrotransposons are discussed in the context of plant genome evolution and breeding.

Sorting Unsigned Permutations by Weighted Reversals,Transpositions,and Transreversals

Reversals, transpositions and transreversals are common events in genome rearrangement. The genome rearrangement sorting problem is to transform one genome into another using the minimum number of given rearrangement operations. An integer permutation is used to represent a genome in many cases. It can be divided into disjoint strips with each strip denoting a block of consecutive integers. A singleton is a strip of one integer. And the genome rearrange- ment problem turns into the problem of sorting a permutation into the identity permutation equivalently. Hannenhalli and Pevzner designed a polynomial time algorithm for the unsigned reversal sorting problem on those permutations with O（logn） singletons. In this paper, first we describe one case in which Hannenhalli and Pevzner＇s algorithm may fail and propose a corrected approach. In addition, we propose a （1 ＋ ε）-approximation algorithm for sorting unsigned permutations with O（log n） singletons by reversals of weight 1 and transpositions/transreversals of weight 2.

Ancient origin and complex evolution of porcine endogenous retroviruses

Porcine endogenous retroviruses(PERVs)are proviruses that have medical value in xenotransplantation.However,the evolutionary process leading to the generation of modern PERVs is not well understood.In this study,we in silico mined 14 pig genomes and other available 304 mammalian genomes,which led to the documentation of 185 full-length PERVs or PERV-like sequences.Notably,we found that lesser Egyptian jerboa(Jaculus jaculus),rock hyrax(Procavia capensis)and eight Muridae species all harbored ancestral PERV-like sequences,indicative of ancient cross-species transmission events from none-porcine species to pigs.We also revealed that 11 genomic rearrangement events were mediated via PERVs,during the process of porcine evolution.In conclusion,these new findings help us to understand the complex evolution of the modern PERVs.