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At least 127 records · Page 7Linked to original sources
PubMed2006

Sequence divergence at the putative flowering time locus COL1 in Brassicaceae.

An insertion/deletion polymorphism (Ind2) in the Brassica nigra CONSTANS LIKE 1 (Bni COL1) gene was previously found to be associated with variation in flowering time. In the present study we examine the inter-specific divergence of COL1 in the family Brassicaceae. Analysis of codon substitution models did not reveal evidence of positive Darwinian selection, but comparisons of the COL1 gene in different species revealed a surprising number of indels. A total of 24 indels were found in the 650 bp of the middle variable region of the gene. This high number of indels could reflect a lack of constraint on length of this region of the protein, or the effect of positive selection. The number of indels was close to that expected in non-coding DNA, but the indels were longer in COL1 than those observed in non-coding regions. Reconstruction of indel evolution indicated that most indels resulted from deletions rather than insertions. The Ind2 indel that has shown association with flowering time in Brassica nigra exhibited a remarkable distribution in the Brassicaceae family, indicating that the polymorphism may have persisted more than ten million years. Considering presumed historic populations sizes of Brassicaceae species, such a long persistence time seems unlikely for a neutral polymorphism.

Arabidopsis Proteins↗
PubMed2006

Automating resequencing-based detection of insertion-deletion polymorphisms.

Structural and insertion-deletion (indel) variants have received considerable recent attention, partly because of their phenotypic consequences. Among these variants, the most common are small indels ( approximately 1-30 bp). Identifying and genotyping indels using sequence traces obtained from diploid samples requires extensive manual review, which makes large-scale studies inconvenient. We report a new algorithm, implemented in available software (PolyPhred version 6.0), to help automate detection and genotyping of indels from sequence traces. The algorithm identifies heterozygous individuals, which permits the discovery of low-frequency indels. It finds 80% of all indel polymorphisms with almost no false positives and finds 97% with a false discovery rate of 10%. Additionally, genotyping accuracy exceeds 99%, and it correctly infers indel length in 96% of the cases. Using this approach, we identify indels in the HapMap ENCODE regions, providing the first report of these polymorphisms in this data set.

Algorithms↗
PubMed2006

Optimal intron analyses in the trimeresurus radiation of Asian pitvipers.

Nuclear introns are commonly used as phylogenetic markers, but a number of issues related to alignment strategies, indel treatments, and the incorporation of length-variant heterozygotes (LVHs) are not routinely addressed when generating phylogenetic hypotheses. Topological congruence in relation to an extensive mitochondrial DNA multigene phylogeny (derived from 2,423 bp of 12S, 16S, ND4, and CYTB genes) of the Asian pitviper Trimeresurus radiation was used to compare combinations of "by eye" and edited and unedited ClustalX 1.8 alignments of two nuclear introns. Indels were treated as missing data, fifth character states, and assigned simple and multistate codes. Upon recovery of the optimal alignment and indel treatment strategy, a total evidence approach was used to investigate the phylogenetic utility of the indels and test new generic arrangements within Trimeresurus. Approximately one third of the intron data partitions exhibited LVHs, suggesting that they are common in introns. Furthermore, a simple concatenation approach can facilitate the incorporation of LVHs into phylogenetic analyses to make use of all available data and investigate mechanisms of molecular evolution. Analyses of ClustalX 1.8-assisted alignments were generally more congruent than the "by eye" alignment and the analysis of a simple coded, edited ClustalX 1.8 (gap opening cost 5, gap extension cost 1) alignment revealed the most congruent tree. The total evidence approach supported the new arrangements within Trimeresurus, suggesting that the phylogeny should be considered as a working benchmark in Asian pitviper systematics. Finally, a critical appraisal of the diverse array of indels (56 to 57 per intron, ranging from 1 to 151 bp in length) suggested that they are a combination of Hennigian and homoplasious events unrelated to indel size or location within the intron. [Alignment; indels; intron analysis; length-variant heterozygotes; Trimeresurus.].

Animals↗
PubMed2002

Human diallelic insertion/deletion polymorphisms.

We report the identification and characterization of 2,000 human diallelic insertion/deletion polymorphisms (indels) distributed throughout the human genome. Candidate indels were identified by comparison of overlapping genomic or cDNA sequences. Average confirmation rate for indels with a > or =2-nt allele-length difference was 58%, but the confirmation rate for indels with a 1-nt length difference was only 14%. The vast majority of the human diallelic indels were monomorphic in chimpanzees and gorillas. The ratio of deletionrcolon;insertion mutations was 4.1. Allele frequencies for the indels were measured in Europeans, Africans, Japanese, and Native Americans. New alleles were generally lower in frequency than old alleles. This tendency was most pronounced for the Africans, who are likely to be closest among the four groups to the original modern human population. Diallelic indels comprise approximately 8% of all human polymorphisms. Their abundance and ease of analysis make them useful for many applications.

Biological Evolution↗
PubMed1999

Evolution of the mitochondrial rps3 intron in perennial and annual angiosperms and homology to nad5 intron 1.

The plant mitochondrial rps3 intron was analyzed for substitution and indel rate variation among 15 monocot and dicot angiosperms from 10 genera, including perennial and annual taxa. Overall, the intron sequence was very conserved among angiosperms. Based on length polymorphism, 10 different alleles were identified among the 10 genera. These allelic differences were mainly attributable to large indels. An insertion of 133 nucleotides, observed in the Alnus intron was partially or completely absent in the other lineages of the family Betulaceae. This insertion was located within domain IV of the secondary-structure model of this group IIA intron. A mobile element of 47 nucleotides that showed homology to sequences located in rice rps3 intron and in intergenic plant mitochondrial genomes was found within this insertion. Both substitution and indel rates were low among the Betulaceae sequences, but substitution rates were increasingly larger than indel rates in comparisons involving more distantly related taxa. From a secondary-structure model, regions involved in helical structures were shown to be well preserved from indels as compared to substitutions, but compensatory changes were not observed among the angiosperm sequences analyzed. Using approximate divergence times based on the fossil record, substitution and indel rate heterogeneity was observed between different pairs of annual and perennial taxa. In particular, the annual petunia and primrose evolved more than 15 and 10 times faster, for substitution and indel rates respectively, than the perennial birch and alder. This is the first demonstration of an evolutionary rate difference between perennial and annual forms in noncoding DNA, lending support to neutral causes such as the generation time, population size, and speciation rate effects to explain such rate heterogeneity. Surprisingly, the sequence from the rps3 intron had a high identity with the sequence of intron 1 from the angiosperm mitochondrial nad5 gene, suggesting a common origin of these two group IIA introns.

Base Sequence↗
PubMed2004

Development of genome-wide DNA polymorphism database for map-based cloning of rice genes.

DNA polymorphism is the basis to develop molecular markers that are widely used in genetic mapping today. A genome-wide rice (Oryza sativa) DNA polymorphism database has been constructed in this work using the genomes of Nipponbare, a cultivar of japonica, and 93-11, a cultivar of indica. This database contains 1,703,176 single nucleotide polymorphisms (SNPs) and 479,406 Insertion/Deletions (InDels), approximately one SNP every 268 bp and one InDel every 953 bp in rice genome. Both SNPs and InDels in the database were experimentally validated. Of 109 randomly selected SNPs, 107 SNPs (98.2%) are accurate. PCR analysis indicated that 90% (97 of 108) of InDels in the database could be used as molecular markers, and 68% to 89% of the 97 InDel markers have polymorphisms between other indica cultivars (Guang-lu-ai 4 and Long-te-pu B) and japonica cultivars (Zhong-hua 11 and 9522). This suggests that this database can be used not only for Nipponbare and 93-11, but also for other japonica and indica cultivars. While validating InDel polymorphisms in the database, a set of InDel markers with each chromosome 3 to 5 marker was developed. These markers are inexpensive and easy to use, and can be used for any combination of japonica and indica cultivars used in this work. This rice DNA polymorphism database will be a valuable resource and important tool for map-based cloning of rice gene, as well as in other various research on rice (http://shenghuan.shnu.edu.cn/ricemarker).

Base Sequence↗
PubMed2026

Comparisons Between Large-Scale Genomic Variants and SNPs in Driving Population Divergence and Local Adaptation.

Genomic variations, such as indels (2-49 bp) and structural variants (SVs, ≥50 bp), are larger-scale mutations than single nucleotide polymorphisms (SNPs) and can substantially impact evolutionary processes, including speciation, adaptation, and phenotypes. Despite their functional importance, integrative population genetic analyses that jointly consider genome-wide SNPs, indels, and SVs remain under-explored. The ground tit (Pseudopodoces humilis), an endemic species to the Qinghai-Tibet Plateau (QTP), exhibits divergence across distinct glacial refugia, accompanied by habitat and morphological divergence, making it an excellent example for investigating how different types of genomic variants contribute to population divergence and local adaptation. Here, by retrieving 81 whole-genome sequence data, over 13 million SNPs, 2 million indels, and 22,101 SVs were identified. Variants were unevenly distributed across the genome, characterized by distinct hotspot regions. Indels and SVs revealed four genetic clusters consistent with previous SNP-based results, thereby validating the reliability of our variant datasets. FST and genotype-environment association (GEA) analyses independently revealed numerous candidate indels and SVs; each showed minimal overlap with previously identified SNPs, and were enriched in similar functional pathways such as signal transduction, skeletal muscle development, water transport, DNA repair, reproduction, nervous system development, and immunity. Collectively, our results demonstrated that indels and SVs could capture additional signatures besides SNPs. Furthermore, similar but distinct gene functions among different types of genomic variants collectively and complementarily drive genomic divergence across environmental gradients in such a high-elevation endemic species, underscoring its evolutionary relevance in local adaptation.

indels↗
PubMed1992

Analysis of insertions/deletions in protein structures.

An analysis of insertions and deletions (indels) occurring in a databank of multiple sequence alignments based on protein tertiary structure is reported. Indels prefer to be short (1 to 5 residues). The average intervening sequence length between them versus the percentage of residue identity in pairwise alignments shows an exponential behaviour, suggesting a stochastic process such that nearly every loop in an ancestral structure is a possible target for indels during evolution. The results also suggest a limit to the average size of indels accommodated by protein structures. The preferred indel conformations are reverse turn and coil as are the preferred conformations at the indel edges (N- and C-terminal sides). Interruptions in helices and strands were observed as very rare events.

Amino Acid Sequence↗
PubMed2002

DNA loss and evolution of genome size in Drosophila.

Mutation is often said to be random. Although it must be true that mutation is ignorant about the adaptive needs of the organism and thus is random relative to them as a rule, mutation is not truly random in other respects. Nucleotide substitutions, deletions, insertions, inversions, duplications and other types of mutation occur at different rates and are effected by different mechanisms. Moreover the rates of different mutations vary from organism to organism. Differences in mutational biases, along with natural selection, could impact gene and genome evolution in important ways. For instance, several recent studies have suggested that differences in insertion/deletion biases lead to profound differences in the rate of DNA loss in animals and that this difference per se can lead to significant changes in genome size. In particular, Drosophila melanogaster appears to have a very high rate of deletions and the correspondingly high rate of DNA loss and a very compact genome. To assess the validity of these studies we must first assess the validity of the measurements of indel biases themselves. Here I demonstrate the robustness of indel bias measurements in Drosophila, by comparing indel patterns in different types of nonfunctional sequences. The indel pattern and the high rate of DNA loss appears to be shared by all known nonfunctional sequences, both euchromatic and heterochromatic, transposable and non-transposable, repetitive and unique. Unfortunately all available nonfunctional sequences are untranscribed and thus effects of transcription on indel bias cannot be assessed. I also discuss in detail why it is unlikely that natural selection for or against DNA loss significantly affects current estimates of indel biases.

Animals↗
PubMed2005

DNA assembly with gaps (Dawg): simulating sequence evolution.

MOTIVATION: Relationships amongst taxa are inferred from biological data using phylogenetic methods and procedures. Very few known phylogenies exist against which to test the accuracy of our inferences. Therefore, in the absence of biological data, simulated data must be used to test the accuracy of methods which produce these inferences. Researchers have limited or non-existent options for simulations useful for studying the impact of insertions, deletions, and alignments on phylogenetic accuracy. RESULTS: To satisfy this gap I have developed a new algorithm of indel formation and incorporated it into a new, flexible, and portable application for sequence simulation. The application, called Dawg, simulates phylogenetic evolution of DNA sequences in continuous time using the robust general time reversible model with gamma and invariant rate heterogeneity and a novel length-dependent model of indel formation. On completion, Dawg produces the true alignment of the simulated sequences. Unlike other applications, Dawg allows indel lengths to be explicitly distributed via a biologically realistic power law. Many options are available to allow users to customize their simulations and results. Because simulating with indels would be problematic if biologically realistic parameters could not be estimated, a script is provided with Dawg that can estimate the parameters of indel formation from sequence data. Dawg was applied to the sequences of four chloroplast trnK introns. It was used to parametrically bootstrap an estimation of the rate of indel formation for the phylogeny. Because Dawg can assist in parametric bootstrapping of sequence data it is useful beyond phylogenetics, such as studying alignment algorithms or parameters of molecular evolution. AVAILABILITY: Dawg 1.0.0 can be obtained at the following websites: http://www.genetics.uga.edu/sw/ or http://scit.us/dawg/. The package includes source code, example files, a brief manual and helper scripts. Binary distributions are available for Windows and Macintosh OS X. A development page for Dawg exists at http://scit.us/dawg/, with links to a Subversion repository, mailing lists and updated versions.

Base Sequence↗
PubMed2006

Rooting the tree of life using nonubiquitous genes.

Insertion and deletion (indel)-based analyses have great potential for rooting the tree of life, but their use has been limited because they require ubiquitous sequences that have not been horizontally/laterally transferred. Very few such sequences exist. Here we describe and demonstrate a new algorithm that can use nonubiquitous sequences for rooting. This algorithm, top-down indel rooting, uses the traditional logical framework of indel rooting, but by considering gene gains and losses in addition to indel gains and losses, it is able to analyze incomplete data sets. The method is demonstrated using theoretical examples and incomplete gene sets. In particular, it is applied to the well-studied Hsp70/MreB indel, a sequence set thought to have been compromised by gene transfers from Firmicutes to archaebacteria. By sequentially assigning all observable character states, including gene absences, to the questionable archaebacterial Hsp70 and MreB sequences, we demonstrate that this gene set robustly excludes the root of the tree of life from the Gram-negative, double-membrane prokaryotes independently of the archaeal character states. There are very few ubiquitous paralog gene sets, and most of them contain compromised data. The ability of top-down rooting to use incomplete and/or compromised gene sets promises to make rooting analyses more robust and to greatly increase the number of useful indel sets.

Algorithms↗
PubMed2004

Occurrence and consequences of coding sequence insertions and deletions in Mammalian genomes.

Nucleotide insertion and deletion (indel) events, together with substitutions, represent the major mutational processes of gene evolution. Through the alignment of 8148 orthologous genes from human, mouse, and rat, we have identified 1743 indel events within rodent protein-coding sequences. Using human as an out-group, we reconstructed the mutational event underlying each of these indels. Overall, we found an excess of deletions over insertions, particularly for the rat lineage (70% excess). Sequence slippage accounts for at least 52% of insertions and 38% of deletions. We have also evaluated the selective tolerance of identifiable protein structures to indels. Transmembrane domains are the least, and low complexity regions, the most tolerant. Mapping of indels onto known protein structures demonstrated that structural cores are markedly less tolerant to indels than are loop regions. There is a specific enrichment of CpG dinucleotides in close proximity to insertion events, and both insertions and deletions are more common in higher G+C content sequences.

Amino Acid Sequence↗
PubMed2006

Analysis of the genome-wide variations among multiple strains of the plant pathogenic bacterium Xylella fastidiosa.

BACKGROUND: The Gram-negative, xylem-limited phytopathogenic bacterium Xylella fastidiosa is responsible for causing economically important diseases in grapevine, citrus and many other plant species. Despite its economic impact, relatively little is known about the genomic variations among strains isolated from different hosts and their influence on the population genetics of this pathogen. With the availability of genome sequence information for four strains, it is now possible to perform genome-wide analyses to identify and categorize such DNA variations and to understand their influence on strain functional divergence. RESULTS: There are 1,579 genes and 194 non-coding homologous sequences present in the genomes of all four strains, representing a 76. 2% conservation of the sequenced genome. About 60% of the X. fastidiosa unique sequences exist as tandem gene clusters of 6 or more genes. Multiple alignments identified 12,754 SNPs and 14,449 INDELs in the 1528 common genes and 20,779 SNPs and 10,075 INDELs in the 194 non-coding sequences. The average SNP frequency was 1.08 x 10(-2) per base pair of DNA and the average INDEL frequency was 2.06 x 10(-2) per base pair of DNA. On an average, 60.33% of the SNPs were synonymous type while 39.67% were non-synonymous type. The mutation frequency, primarily in the form of external INDELs was the main type of sequence variation. The relative similarity between the strains was discussed according to the INDEL and SNP differences. The number of genes unique to each strain were 60 (9a5c), 54 (Dixon), 83 (Ann1) and 9 (Temecula-1). A sub-set of the strain specific genes showed significant differences in terms of their codon usage and GC composition from the native genes suggesting their xenologous origin. Tandem repeat analysis of the genomic sequences of the four strains identified associations of repeat sequences with hypothetical and phage related functions. CONCLUSION: INDELs and strain specific genes have been identified as the main source of variations among strains, with individual strains showing different rates of genome evolution. Based on these genome comparisons, it appears that the Pierce's disease strain Temecula-1 genome represents the ancestral genome of the X. fastidiosa. Results of this analysis are publicly available in the form of a web database.

Analysis of Variance↗
PubMed1993

Empirical and structural models for insertions and deletions in the divergent evolution of proteins.

The exhaustive matching of the protein sequence database makes possible a broadly based study of insertions and deletions (indels) during divergent evolution. In this study, the probability of a gap in an alignment of a pair of homologous protein sequences was found to increase with the evolutionary distance measured in PAM units (number of accepted point mutations per 100 amino acid residues). A relationship between the average number of amino acid residues between indels and evolutionary distance suggests that a unit 30 to 40 amino acid residues in length remains, on average, undisrupted by indels during divergent evolution. Further, the probability of a gap was found to be inversely proportional to gap length raised to the 1.7 power. This empirical law fits closely over the entire range of gap lengths examined. Gap length distribution is largely independent of evolutionary distance. These results rule out the widely used linear gap penalty as a satisfactory formula for scoring gaps when constructing alignments. Further, the observed gap length distribution can be explained by a simple model of selective pressures governing the acceptance of indels during divergent evolution. Finally, this model provides theoretical support for using indels as part of "parsing algorithms", important in the de novo prediction of the folded structure of proteins from the sequence data.

Amino Acid Sequence↗
PubMed2003

Sequence alignments and pair hidden Markov models using evolutionary history.

This work presents a novel pairwise statistical alignment method based on an explicit evolutionary model of insertions and deletions (indels). Indel events of any length are possible according to a geometric distribution. The geometric distribution parameter, the indel rate, and the evolutionary time are all maximum likelihood estimated from the sequences being aligned. Probability calculations are done using a pair hidden Markov model (HMM) with transition probabilities calculated from the indel parameters. Equations for the transition probabilities make the pair HMM closely approximate the specified indel model. The method provides an optimal alignment, its likelihood, the likelihood of all possible alignments, and the reliability of individual alignment regions. Human alpha and beta-hemoglobin sequences are aligned, as an illustration of the potential utility of this pair HMM approach.

Algorithms↗
PubMed2004

A member of a repeat family is the source of an insertion-deletion polymorphism inside a developmentally eliminated sequence of Tetrahymena thermophila.

In Tetrahymena thermophila, the development of a transcriptionally active macronucleus from a transcriptionally inert micronucleus is accompanied by the elimination of numerous DNA segments, called internally eliminated sequences (IESs), many of which belong to dispersed repetitive sequence families. To examine the relationship between the insertion and deletion events expected to occur during evolution of the repeats and the developmental elimination process, IESs were compared among different Tetrahymena strains. A 600 base-pair DNA segment, the R Indel, was discovered inside the R IES, one of the ten sequenced IESs out of an estimated 6000 total in the Tetrahymena genome. The R Indel was found in strains B3 and C2 but not in several other strains examined, indicating that the Indel was probably present in a progenitor of strains B3 and C2. The R Indel was found to belong to a moderately large sequence family of about 200 members; however, BLAST searches did not reveal meaningful similarities with other mobile elements. Sequence comparisons revealed that a 300 base-pair stretch, very closely related to the first half of the R Indel, was present inside the previously described B IES, another of the ten sequenced IESs. This is the first example of shared sequences between two of the known IESs.

Animals↗
PubMed2004

Empirical analysis of protein insertions and deletions determining parameters for the correct placement of gaps in protein sequence alignments.

To understand how protein segments are inserted and deleted during divergent evolution, a set of pairwise alignments contained exactly one gap, and therefore arising from the first insertion-deletion (indel) event in the time separating the homologs, was examined. The alignments showed that "structure breaking" amino acids (PGDNS) were preferred within and flanking gapped regions, as are two residues with hydrophilic side-chains (QE) that frequently occur at the surface of protein folds. Conversely, hydrophobic residues (FMILYVW) occur infrequently within and flanking the gapped region. These preferences are modestly different in protein pairs separated by an episode of adaptive evolution, than in pairs diverging under strong functional constraints. Surprisingly, regions near an indel have not evolved more rapidly than the sequence pair overall, showing no evidence that an indel event must be compensated by local amino acid replacement. The gap-lengths are best approximated by a Zipfian distribution, with the probability of a gap of length L decreasing as a function of L(-1.8). These features are largely independent of the length of the gap and the extent of divergence (measured by both silent and non-silent sequence changes) separating the two proteins. Surprisingly, amino acid repeats were discovered in more than a third of the polypeptide segments in and around the gap. These correspond to repeats in the DNA sequence. This suggests that a signature of the mechanism by which indels occur in the DNA sequence remains in the encoded protein sequences. These data suggest specific tools to score gap placement in an alignment. They also suggest tools that distinguish true indels from gaps created by mistaken gene finding, including under-predicted and over-predicted introns. By providing mechanisms to identify errors, the tools will enhance the value of genome sequence databases in support of integrated paleogenomics strategies used to extract functional information in a post-genomic environment.

Amino Acid Sequence↗
PubMed2003

First-generation SNP/InDel markers tagging loci for pathogen resistance in the potato genome.

A panel of 17 tetraploid and 11 diploid potato genotypes was screened by comparative sequence analysis of polymerase chain reaction (PCR) products for single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (InDels), in regions of the potato genome where genes for qualitative and/or quantitative resistance to different pathogens have been localized. Most SNP and InDel markers were derived from bacterial artificial chromosome (BAC) insertions that contain sequences similar to the family of plant genes for pathogen resistance having nucleotide-binding-site and leucine-rich-repeat domains (NBS-LRR-type genes). Forty-four such NBS-LRR-type genes containing BAC-insertions were mapped to 14 loci, which tag most known resistance quantitative trait loci (QTL) in potato. Resistance QTL not linked to known resistance-gene-like (RGL) sequences were tagged with other markers. In total, 78 genomic DNA fragments with an overall length of 31 kb were comparatively sequenced in the panel of 28 genotypes. 1498 SNPs and 127 InDels were identified, which corresponded, on average, to one SNP every 21 base pairs and one InDel every 243 base pairs. The nucleotide diversity of the tetraploid genotypes (pi = 0.72 x 10(-3)) was lower when compared with diploid genotypes (pi = 2.31 x 10(-3)). RGL sequences showed higher nucleotide diversity when compared with other sequences, suggesting evolution by divergent selection. Information on sequences, sequence similarities, SNPs and InDels is provided in a database that can be queried via the Internet.

Journal Article↗