Dataset Information

Partially local three-way alignments and the sequence signatures of mitochondrial genome rearrangements.

ABSTRACT: BACKGROUND:Genomic DNA frequently undergoes rearrangement of the gene order that can be localized by comparing the two DNA sequences. In mitochondrial genomes different mechanisms are likely at work, at least some of which involve the duplication of sequence around the location of the apparent breakpoints. We hypothesize that these different mechanisms of genome rearrangement leave distinctive sequence footprints. In order to study such effects it is important to locate the breakpoint positions with precision. RESULTS:We define a partially local sequence alignment problem that assumes that following a rearrangement of a sequence F, two fragments L, and R are produced that may exactly fit together to match F, leave a gap of deleted DNA between L and R, or overlap with each other. We show that this alignment problem can be solved by dynamic programming in cubic space and time. We apply the new method to evaluate rearrangements of animal mitogenomes and find that a surprisingly large fraction of these events involved local sequence duplications. CONCLUSIONS:The partially local sequence alignment method is an effective way to investigate the mechanism of genomic rearrangement events. While applied here only to mitogenomes there is no reason why the method could not be used to also consider rearrangements in nuclear genomes.

SUBMITTER: Al Arab M

PROVIDER: S-EPMC5569537 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Partially local three-way alignments and the sequence signatures of mitochondrial genome rearrangements.

Al Arab Marwa M Bernt Matthias M Höner Zu Siederdissen Christian C Tout Kifah K Stadler Peter F PF

Algorithms for molecular biology : AMB 20170823

<h4>Background</h4>Genomic DNA frequently undergoes rearrangement of the gene order that can be localized by comparing the two DNA sequences. In mitochondrial genomes different mechanisms are likely at work, at least some of which involve the duplication of sequence around the location of the apparent breakpoints. We hypothesize that these different mechanisms of genome rearrangement leave distinctive sequence footprints. In order to study such effects it is important to locate the breakpoint po ...[more]

PMID: 28852417

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Project description:BackgroundThe optimal score for ungapped local alignments of infinitely long random sequences is known to follow a Gumbel extreme value distribution. Less is known about the important case, where gaps are allowed. For this case, the distribution is only known empirically in the high-probability region, which is biologically less relevant.ResultsWe provide a method to obtain numerically the biologically relevant rare-event tail of the distribution. The method, which has been outlined in an earlier work, is based on generating the sequences with a parametrized probability distribution, which is biased with respect to the original biological one, in the framework of Metropolis Coupled Markov Chain Monte Carlo. Here, we first present the approach in detail and evaluate the convergence of the algorithm by considering a simple test case. In the earlier work, the method was just applied to one single example case. Therefore, we consider here a large set of parameters: We study the distributions for protein alignment with different substitution matrices (BLOSUM62 and PAM250) and affine gap costs with different parameter values. In the logarithmic phase (large gap costs) it was previously assumed that the Gumbel form still holds, hence the Gumbel distribution is usually used when evaluating p-values in databases. Here we show that for all cases, provided that the sequences are not too long (L > 400), a "modified" Gumbel distribution, i.e. a Gumbel distribution with an additional Gaussian factor is suitable to describe the data. We also provide a "scaling analysis" of the parameters used in the modified Gumbel distribution. Furthermore, via a comparison with BLAST parameters, we show that significance estimations change considerably when using the true distributions as presented here. Finally, we study also the distribution of the sum statistics of the k best alignments.ConclusionOur results show that the statistics of gapped and ungapped local alignments deviates significantly from Gumbel in the rare-event tail. We provide a Gaussian correction to the distribution and an analysis of its scaling behavior for several different scoring parameter sets, which are commonly used to search protein data bases. The case of sum statistics of k best alignments is included.

Project description:BackgroundOrthoptera, the largest polyneopteran insect order, contains 2 suborders and 235 subfamilies. Orthoptera mitochondrial genomes (mitogenomes) follow the ancestral insect gene order, with the exception of a trnD-trnK rearrangement in Acridomorphs and rare tRNA inversions. A question still remains regarding whether a long thymine-nucleotide stretch (T-stretch) involved in the recognition of the replication origin exists in the control region (CR) of Orthoptera mitochondrial DNA (mtDNA). Herein, we completed the sequencing of whole mitogenomes of two congeners (Sinochlora longifissa and S. retrolateralis), which possess overlapping distribution areas. Additionally, we performed comparative mitogenomic analysis to depict evolutionary trends of Orthoptera mitogenomes.ResultsBoth Sinochlora mitogenomes possess 37 genes and one CR, a common gene orientation, normal structures of transfer RNA and ribosomal RNA genes, rather low A+T bias, and significant C skew in the majority strand (J-strand), resembling all the other sequenced ensiferans. Both mitogenomes are characterized by (1) a large size resulting from multiple copies of an approximately 175 bp GC-rich tandem repeat within CR; (2) a novel gene order (rrnS-trnI-trnM-nad2-CR-trnQ-trnW), compared to the ancestral order (rrnS-CR-trnI-trnQ-trnM-nad2-trnW); and (3) redundant trnS(UCN) pseudogenes located between trnS(UCN) and nad1. Multiple independent duplication events followed by random and/or non-random loss occurred during Sinochlora mtDNA evolution. The Orthoptera mtDNA recognition sequence of the replication origin may be one of two kinds: a long T-stretch situated in or adjacent to a possible stem-loop structure or a variant of a long T-stretch located within a potential stem-loop structure.ConclusionsThe unique Sinochlora mitogenomes reveal that the mtDNA architecture within Orthoptera is more variable than previously thought, enriching our knowledge on mitogenomic genetic diversities. The novel genome rearrangements shed light on mtDNA evolutionary patterns. The two kinds of recognition sequences of replication origin suggest that the regulatory sequences involved in the replication initiation process of mtDNA have diverged through Orthoptera evolution.

Project description:BACKGROUND: Analyses of DNA sequences from cultivated microorganisms have revealed genome-wide, taxa-specific nucleotide compositional characteristics, referred to as genome signatures. These signatures have far-reaching implications for understanding genome evolution and potential application in classification of metagenomic sequence fragments. However, little is known regarding the distribution of genome signatures in natural microbial communities or the extent to which environmental factors shape them. RESULTS: We analyzed metagenomic sequence data from two acidophilic biofilm communities, including composite genomes reconstructed for nine archaea, three bacteria, and numerous associated viruses, as well as thousands of unassigned fragments from strain variants and low-abundance organisms. Genome signatures, in the form of tetranucleotide frequencies analyzed by emergent self-organizing maps, segregated sequences from all known populations sharing < 50 to 60% average amino acid identity and revealed previously unknown genomic clusters corresponding to low-abundance organisms and a putative plasmid. Signatures were pervasive genome-wide. Clusters were resolved because intra-genome differences resulting from translational selection or protein adaptation to the intracellular (pH approximately 5) versus extracellular (pH approximately 1) environment were small relative to inter-genome differences. We found that these genome signatures stem from multiple influences but are primarily manifested through codon composition, which we propose is the result of genome-specific mutational biases. CONCLUSIONS: An important conclusion is that shared environmental pressures and interactions among coevolving organisms do not obscure genome signatures in acid mine drainage communities. Thus, genome signatures can be used to assign sequence fragments to populations, an essential prerequisite if metagenomics is to provide ecological and biochemical insights into the functioning of microbial communities.

Dataset Information

Partially local three-way alignments and the sequence signatures of mitochondrial genome rearrangements.

Publications

Partially local three-way alignments and the sequence signatures of mitochondrial genome rearrangements.

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