Transversion Substitutions Research Articles

The Highest Mutation in mtDNA Hypervariable Region and Application of Biostatistics with Nucleotide Base X t-n in Determining the Identity of the Mutation through a Transition Intensity Matrix

Human mitochondrial DNA (mtDNA) have been used intensively in the field of forensic identification of victims or suspects of crime through biological evidence. The number of mtDNA molecules in a single cell are in the tens of thousands which enable analysis of samples very little or damaged. Till now there is no standard method for identification using mtDNA in a mass disaster victims such as natural disasters, wars and accidents so that the identification process can not run fast. This study found C16.223t variants in mtDNA sequences that can be used to divide the database into two groups so as to accelerate the process of identification through a mathematical algorithm. This variant has the highest frequency (29.7%) of the 91 polymorphic human mtDNA HVS1 along the 300 nucleotide (16,024-16,324) derived from the NCBI database as much as 142 sequences. MtDNA sequences obtained from data collection Papuan human mtDNA groups that have been published in the NCBI. The next variant that can be used as a classifier in a row in the sequence is 16,311; 16,304; 16,189; and 16,270 with the identity (T→c). For a matrix Q is reversible so the matrix and could have the opposite diagonal. Thus the above equation can be solved by using the diagonal method that can be written: U³ = Uµ רUµ aµ†1 . This equation could count the number of transitions and transversion substitution mutations that occur in a nucleotide sequence of mtDNA. With this grouping, the database can be reduced so as to accelerate the process of identification of samples. Expected method of grouping by the variant with the highest frequency can be developed in the codification database for forensic interest such as the police or the mtDNA database purposes of study anthropology and evolutionary biology.

Evidence for the Selective Basis of Transition-to-Transversion Substitution Bias in Two RNA Viruses.

The substitution rates of transitions are higher than expected by chance relative to those of transversions. Many have argued that selection disfavors transversions, as nonsynonymous transversions are less likely to conserve biochemical properties of the original amino acid. Only recently has it become feasible to directly test this selective hypothesis by comparing the fitness effects of a large number of transition and transversion mutations. For example, a recent study of six viruses and one beta-lactamase gene did not find evidence supporting the selective hypothesis. Here, we analyze the relative fitness effects of transition and transversion mutations from our recently published genome-wide study of mutational fitness effects in influenza virus. In contrast to prior work, we find that transversions are significantly more detrimental than transitions. Using what we believe to be an improved statistical framework, we also identify a similar trend in two HIV data sets. We further demonstrate a fitness difference in transition and transversion mutations using four deep mutational scanning data sets of influenza virus and HIV, which provided adequate statistical power. We find that three of the most commonly cited radical/conservative amino acid categories are predictive of fitness, supporting their utility in studies of positive selection and codon usage bias. We conclude that selection is a major contributor to the transition:transversion substitution bias in viruses and that this effect is only partially explained by the greater likelihood of transversion mutations to cause radical as opposed to conservative amino acid changes.

An Analysis of Partial DNA Sequence of Meisa1 Gene on Sweet and Bitter Cassavas (Manihot esculenta Crantz.)

<p>Sweet and bitter taste on cassava tuber is affected by starch metabolisms. Meisa1 gene is a gene in cassava (Manihot esculenta Crantz.) encoding isoamylase1 enzyme involved in starch metabolisms. This study aimed to analyze partial DNA sequences of Meisa1 gene on sweet and bitter cassavas collected by Genetics Laboratory, Department Biology, Faculty of Mathematics and Natural Sciences, Riau University, Indonesia. Methods included total DNA extraction from fresh young leaves of cassava using CTAB buffer, polymerase chain reaction (PCR), electrophoresis, and sequencing. The obtained data were analyzed using MEGA software version 5. The results showed that there were nucleotide variations in the intron region, not in the exon region. The variations were caused by the transition substitution mutation (35.39%) and transversion substitution mutation (64.61%). The genetic distance range between seven cassava genotypes was approximately 0% to 11%. Partial DNA sequence variations of Meisa1 gene located in intron region were unable to cluster seven cassava genotypes separately into two groups based on tuber taste.</p><p><strong>How to Cite</strong></p><p>Roslim, D., Nisa, F., & Herman, H. (2016). An Analysis of Partial DNA Sequence of <em>Meisa1</em> Gene on Sweet and Bitter Cassavas (Manihot esculenta Crantz.). <em>Biosaintifika: Journal of Biology & Biology Education</em>, 8(1) 103-110.</p>

Substitution and Haplotype Diversity Analysis on The Partial Sequence of The Mitochondrial DNA Cyt b of Indonesian Swamp Buffalo (Bubalus bubalis)

<p>This research aims to investigate the substitution pattern of nucleotide base and haplotype diversity of Indonesian swamp buffalo (<em>Bubalus bubalis)</em> based on the mitochondrial DNA cyt b partial gene sequence. 17 samples were chosen from 7 different regions with each uniquely represents Indonesian biogeography which comprise Aceh, Riau, Madiun, Blitar, Lombok, South Borneo and Tana Toraja. The result of cyt b gene sequence alignment showed the presence of transition and transversion substitutions and the absence of insertion and deletion. The amount of transitions was found to be higher than that of transversions and the amount of substitution in pyrimidine was also higher than that in purine. The highest amount of transitions happened in base TàC which is a silent substitution. The result of median joining network analysis showed that Indonesian haplotype<em> Bubalus bubalis</em> could be classified into 16 haplotypes which form different haplogroups unique to their geographical region. The result of median joining network<em> </em>analysis also indicated that the genetic relationships of swamp buffaloes (<em>Bubalus bubalis) </em>in Indonesia are highly influenced by their geographical locations.</p>

DNA barcoding and molecular evolution of mosquito vectors of medical and veterinary importance.

Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating pathogens and parasites. The standard method of utilisation of morphological characters becomes challenging due to various factors such as phenotypical variations. We explored the complementary approach of CO1 gene-based identification, analysing ten species of mosquito vectors belonging to three genera, Aedes, Culex and Anopheles from India. Analysed nucleotide sequences were found without pseudo genes and indels; they match with high similarity in nucleotide Basic Local Alignment Search Tool (BLASTn) search. The partial CO1 sequence of Anopheles niligricus was the first time record submitted to National Center for Biotechnology Information (NCBI). Mean intra- and interspecies divergence was found to be 1.30 and 3.83 %, respectively. The congeneric divergence was three times higher than the conspecifics. Deep intraspecific divergence was noted in three of the species, and the reason could be explained more accurately in the future by improving the sample size across different locations. The transitional and transversional substitutions were tested individually. Ts and Tv substitutions in all the 1st, 2nd and 3rd codons were estimated to be (0.44, 99.51), (40.35, 59.66) and (59.16, 40.84), respectively. Saturation of the sequences was resolved, since both the Ts and Tv exhibited a linear relationship suggesting that the sequences were not saturated. NJ and ML tree analysis showed that the individuals of the same species clustered together based on the CO1 sequence similarity, regardless of their collection site and geographic location. Overall, this study adds basic knowledge to molecular evolution of mosquito vectors of medical and veterinary importance and may be useful to improve biotechnological tools employed in Culicidae control programmes.

Polymorphism of The Promote Region of Chicken Insulin like Growth Factor-1 and Association With Bone Abnormalitiesالتغ

The insulin like growth factor-1(IGF-1) is important regulators in stimulating growth, proteinsynthesis, cell proliferation and differentiation in a variety of cell types. To achieve this goal,blood samples were collected from 50 Gallus gallus affected from bone abnormalities (distortion)and 50 samples a control group from the Animal farm/ College of Veterinary medicine/University of Baghdad. DNA was isolated and the IGF-1genewas amplified by using specificprimers for promoter region and 5' UTR of this genes, then DNA sequencing was performed byusing AB13730XL, (Applied Bio system, Macro Gen company, USA). The DNA sequencingresults of flank sense of IGF-1gene from a control group was found to be compatible 100% withwild type of Gallus gallus from the Gene Bank. On the other hand, sequencing results of the samegene from 35cases abnormalities (distortion) revealed of 99% compatible and score 1351 andexpect 0.0 with the wild type sequences of gene bank. The minor differences could be attributedto two transversion substitutions of (G>T,T>G) and (C>T) on locations 404, 104, and 249 nucleicacid respectability. Fifteen cases of bone abnormalities (Distortion) of Gallus gallus, 99%compatibility have one Transversion substitution G>T on position 404 andone transitionsubstitution (C>T) on 249 positions, under number Sequence ID: gb|JX414253.1|. In conclusion,our case study suggests that polymorphisms of IGF-1gene are strongly associated with vertebrategrowth and development of some chicken breeds in Iraq. The aim of this study is to identify thegenetic polymorphisms of IGF-1gene and its association with vertebrate growth and developmentof some chicken breeds in Iraq.

Genetic Variation Among the Geographic Population of the Grain Aphid, Sitobion avenae (Hemiptera: Aphididae) in China Inferred from Mitochondrial COI Gene Sequence

In order to characterize the genetic relationship of the geographic populations of Sitobion avenae (Hemiptera: Aphididae) in China, a 588 bp region of the mitochondrial cytochrome oxidase subunit I (mtDNA-COI) gene was sequenced and analyzed among the different geographic populations. 269 individuals were collected from 17 localities in different wheat-growing areas in China that covered most of the range reported for this species. Within the sequence among these geographic populations, 15 polymorphic sites defined 16 distinct haplotypes, ranging in sequence divergence from 0.2% (one nucleotide) to 1.7% (10 nucleotides). Of the 15 variable sites, 12 were transitional substitutions, 2 were transversional substitutions and 1 was transitional and transversional substitution. Phylogenetic analysis showed that all haplotypes were highly interconnected with each other, in absence of phylogeographic structing. Each of 8 haplotypes was found only at one locality, and the other haplotypes were the widespread distributed in the different localities. The higher genetic diversity was found in the northern China populations than that in the southern China populations. The low genetic differentiation ( F ST=−0.06945-0.69857) and high migration rate (Nm=0.21575-infinite) of Chinese populations suggest that dispersal over long distance is a major factor in the demography of S. avenae.

Genotoxicity of pyrrolizidine alkaloids

Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs.

Compensatory Evolution in RNA Secondary Structures Increases Substitution Rate Variation among Sites

There is growing evidence that interactions between biological molecules (e.g., RNA-RNA, protein-protein, RNA-protein) place limits on the rate and trajectory of molecular evolution. Here, by extending Kimura's model of compensatory evolution at interacting sites, we show that the ratio of transition to transversion substitutions (kappa) at interacting sites should be equal to the square of the ratio at independent sites. Because transition mutations generally occur at a higher rate than transversions, the model predicts that kappa should be higher at interacting sites than at independent sites. We tested this prediction in 10 RNA secondary structures by comparing phylogenetically derived estimates of kappa in paired sites within stems (kappa(p)) and unpaired sites within loops (kappa(u)). Eight of the 10 structures showed an excellent match to the quantitative predictions of the model, and 9 of the 10 structures matched the qualitative prediction kappa(p) > kappa(u). Only the Rev response element from the human immunovirus (HIV) genome showed the reverse pattern, with kappa(p) < kappa(u). Although a variety of evolutionary forces could produce quantitative deviations from the model predictions, the reversal in magnitude of kappa(p) and kappa(u) could be achieved only by violating the model assumption that the underlying transition (or transversion) mutation rates were identical in paired and unpaired regions of the molecule. We explore the ability of the APOBEC3 enzymes, host defense mechanisms against retroviruses, which induce transition mutations preferentially in single-stranded regions of the HIV genome, to explain this exception to the rule. Taken as a whole, our findings suggest that kappa may have utility as a simple diagnostic to evaluate proposed secondary structures.

Phylogeny and molecular genetic parameters of different stages of hepatitis B virus infection in patients from the Brazilian Amazon

A fragment of 600 bp of the gene which codes for the surface antigen of hepatitis B virus (HBV) was amplified and sequenced from patients who were born in five states of the Brazilian Amazon (Amazonas, Pará, Acre, Rondônia and Tocantins). A total of 44 sequences were used for the estimation of molecular genetic parameters and phylogenetic analyses. Compared with patients who were asymptomatic, those who had acute hepatitis and chronic liver disease had higher levels of genetic variability and higher rates of nucleotide substitutions. The analysis of transition and transversion substitutions showed that transition-type substitutions predominated. In chronic liver disease carriers, transversion-type substitutions showed phylogenetic saturation. In general, all of the analyses carried out in this study showed an association between patterns of changes in molecular genetic parameters and the stage of disease progression. Phylogenetic analysis using the HKY85 model of evolution identified 41 individuals as genotype A, suggesting its predominance in the Amazon region, one individual as genotype C, and one individual closely related to genotypes E and F.

Cytochrome-b sequence variation among parrots.

The nucleotide sequence of a 307 bp fragment of the mitochondrial cytochrome-b gene was determined for 12 species of parrot, using the polymerase chain reaction and direct sequencing. Sequence divergence ranged from 26-54 differences in pairwise comparisons, with the majority of base substitutions occurring at third positions of codons. The transition:transversion ratio was determined to be higher (approximately 24.3:1) in recently divergent parrot lineages than has generally been observed in other groups. Strongly biased base composition, particularly at the third position of codons, is evident among the sequences. Phylogenetic relationships among more divergent taxa were estimated, using only transversion substitutions, while all the substitutions were useful for closely related taxa. The African genera Psittacus and Poicephalus are closely related, in contrast to the Australian genera Nymphicus, Purpureicephalus and Melopsittacus, which represent more divergent lineages. The cockatoos appear to represent an ancient lineage within the parrots.

Simulating DNA Coding Sequence Evolution with EvolveAGene 3

Phylogenetic reconstruction based upon multiple alignments of molecular sequences is important to most branches of modern biology and is central to molecular evolution. Understanding the historical relationships among macromolecules depends upon computer programs that implement a variety of analytical methods. Because it is impossible to know those historical relationships with certainty, assessment of the accuracy of methods and the programs that implement them requires the use of programs that realistically simulate the evolution of DNA sequences. EvolveAGene 3 is a realistic coding sequence simulation program that separates mutation from selection and allows the user to set selection conditions, including variable regions of selection intensity within the sequence and variation in intensity of selection over branches. Variation includes base substitutions, insertions, and deletions. To the best of my knowledge, it is the only program available that simulates the evolution of intact coding sequences. Output includes the true tree and true alignments of the resulting coding sequence and corresponding protein sequences. A log file reports the frequencies of each kind of base substitution, the ratio of transition to transversion substitutions, the ratio of indel to base substitution mutations, and the numbers of silent and amino acid replacement mutations. The realism of the data sets has been assessed by comparing the d(N)/d(S) ratio, the ratio of transition to transversion substitutions, and the ratio of indel to base substitution mutations of the simulated data sets with those parameters of real data sets from the "gold standard" BaliBase collection of structural alignments. Results show that the data sets produced by EvolveAGene 3 are very similar to real data sets, and EvolveAGene 3 is therefore a realistic simulation program that can be used to evaluate a variety of programs and methods in molecular evolution.

Transition-Transversion Bias Is Not Universal: A Counter Example from Grasshopper Pseudogenes

Comparisons of the DNA sequences of metazoa show an excess of transitional over transversional substitutions. Part of this bias is due to the relatively high rate of mutation of methylated cytosines to thymine. Postmutation processes also introduce a bias, particularly selection for codon-usage bias in coding regions. It is generally assumed, however, that there is a universal bias in favour of transitions over transversions, possibly as a result of the underlying chemistry of mutation. Surprisingly, this underlying trend has been evaluated only in two types of metazoan, namely Drosophila and the Mammalia. Here, we investigate a third group, and find no such bias. We characterize the point substitution spectrum in Podisma pedestris, a grasshopper species with a very large genome. The accumulation of mutations was surveyed in two pseudogene families, nuclear mitochondrial and ribosomal DNA sequences. The cytosine-guanine (CpG) dinucleotides exhibit the high transition frequencies expected of methylated sites. The transition rate at other cytosine residues is significantly lower. After accounting for this methylation effect, there is no significant difference between transition and transversion rates. These results contrast with reports from other taxa and lead us to reject the hypothesis of a universal transition/transversion bias. Instead we suggest fundamental interspecific differences in point substitution processes.

Genetic variation in the diamondback moth, Plutella xylostella (Lepidoptera: Yponomeutidae) in China inferred from mitochondrial COI gene sequence

The diamondback moth, Plutella xylostella (L.), is a notorious insect pest of cruciferous plants. To examine the pattern and magnitude of genetic variation in this species in China a portion of the mitochondrial (mt) COI gene of P. xylostella, collected at six Chinese and two Korean localities, which cover ~2,151,600 km 2 , was sequenced. Sequence analysis of the 681-bp mt COI gene from 80 individuals resulted in 16 haplotypes, ranging in sequence divergence from 0.1% (one nucleotide) to 0.9% (six nucleotides). One nucleotide position among 16 variable sites was a transversional substitution and the remaining positions were transitional sub- stitutions. No position resulted in amino acid substitution. Phylogenetic analysis showed that all haplotypes were highly interrelated and no discernable haplotype group was found. From a geographical perspective, most haplotypes were found singly at one or two localities, with three haplotypes widely distributed. Little genetic differentiation (FST = -0.038-0.309) and a high rate of female migration (Nm = 1.117 - infinite) between Chinese populations suggests that dispersal over long distances is a major factor in the demography of this species.

Computing Ka and Ks with a consideration of unequal transitional substitutions

BackgroundApproximate methods for estimating nonsynonymous and synonymous substitution rates (Ka and Ks) among protein-coding sequences have adopted different mutation (substitution) models. In the past two decades, several methods have been proposed but they have not considered unequal transitional substitutions (between the two purines, A and G, or the two pyrimidines, T and C) that become apparent when sequences data to be compared are vast and significantly diverged.ResultsWe propose a new method (MYN), a modified version of the Yang-Nielsen algorithm (YN), for evolutionary analysis of protein-coding sequences in general. MYN adopts the Tamura-Nei Model that considers the difference among rates of transitional and transversional substitutions as well as factors in codon frequency bias. We evaluate the performance of MYN by comparing to other methods, especially to YN, and to show that MYN has minimal deviations when parameters vary within normal ranges defined by empirical data.ConclusionOur comparative results deriving from consistency analysis, computer simulations and authentic datasets, indicate that ignoring unequal transitional rates may lead to serious biases and that MYN performs well in most of the tested cases. These results also suggest that acquisitions of reliable synonymous and nonsynonymous substitution rates primarily depend on less biased estimates of transition/transversion rate ratio.

Phylogeny and biogeography of the Petaurista philippensis complex (Rodentia: Sciuridae), inter- and intraspecific relationships inferred from molecular and morphometric analysis

With modified DNA extraction and purification protocols, the complete cytochrome b gene sequences (1140 bp) were determined from degraded museum specimens. Molecular analysis and morphological examination of cranial characteristics of the giant flying squirrels of Petaurista philippensis complex ( P. grandis, P. hainana, and P. yunanensis) and other Petaurista species yielded new insights into long-standing controversies in the Petaurista systematics. Patterns of genetic variations and morphological differences observed in this study indicate that P. hainana, P. albiventer, and P. yunanensis can be recognized as distinct species, and P. grandis and P. petaurista are conspecific populations. Phylogenetic relationships reconstructed by using parsimony, likelihood, and Bayesian methods reveal that, with P. leucogenys as the basal branch, all Petaurista groups formed two distinct clades. Petaurista philippensis, P. hainana, P. yunanensis, and P. albiventer are clustered in the same clade, while P. grandis shows a close relationship to P. petaurista. Deduced divergence times based on Bayesian analysis and the transversional substitution at the third codon suggest that the retreating of glaciers and upheavals or movements of tectonic plates in the Pliocene–Pleistocene were the major factors responsible for the present geographical distributions of Petaurista groups.

Detecting gradients of asymmetry in site-specific substitutions in mitochondrial genomes.

During mitochondrial replication, spontaneous mutations occur and accumulate asymmetrically during the time spent single stranded by the heavy strand (DssH). The predominant mutations appear to be deaminations from adenine to hypoxanthine (A --> H, which leads to an A --> G substitution) and cytosine to thymine (C --> T). Previous findings indicated that C --> T substitutions accumulate rapidly and then saturate at high DssH, suggesting protection or repair, whereas A --> G accumulates linearly with DssH. We describe here the implementation of a simple hidden Markov model (HMM) of among-site rate correlations to provide an almost continuous profile of the asymmetry in substitution response for any particular substitution type. We implement this model using a phylogeny-based Bayesian Markov chain Monte Carlo (MCMC) approach. We compare and contrast the relative asymmetries in all 12 possible substitution types, and find that the observed transition substitution responses determined using our new method agree quite well with previous predictions of a saturating curve for C --> T transition substitutions and a linear accumulation of A --> G transitions. The patterns seen in transversion substitutions show much lower among-site variation, and are nonlinear and more complex than those seen in transitions. We also find that, after accounting for the principal linear effect, some of the residual variation in A --> G/G --> A response ratios is explained by the average predicted nucleic acid secondary structure propensity at a site, possibly due to protection from mutation when secondary structure forms.

A preliminary study on the genetic diversity of small populations of two flying squirrel species from Pakistan (Hylopetes fimbriatus and Petaurista petaurista albiventer), based on mitochondrial DNA control region sequences

We undertook a preliminary investigation on the population genetics of two flying squirrel species (Hylopetes fimbriatus and Petaurista petaurista albiventer) that are endemic to the northwestern Himalayan range. These species are distributed sympatrically, share similar ecological characteristics, and are confined to the Himalayan moist temperate forests ranging from 1350 to 3050 m elevation. To elucidate the genetic variability of small populations of these species, we determined the complete mitochondrial DNA control region sequence of H. fimbriatus (1109 bp) and P. petaurista albiventer (1051–1052 bp), collected at the Ayubia National Park of northern Pakistan. Haplotype and nucleotide diversities and average number of nucleotide differences among haplotypes of H. fimbriatus were similar to those of P. petaurista albiventer. However, transversional substitutions among haplotypes of H. fimbriatus were significantly greater than that of P. petaurista albiventer. This latter difference may have arisen from climatic changes during recent Pleistocene glaciations that differentially affected the distribution patterns of these two species. For instance, H. fimbriatus, which is more adaptive to colder and drier habitats, may have maintained a larger population base in the northwestern Himalayan range than P. petaurista albiventer. Alternatively, H. fimbriatus might have colonized the northwestern parts of the Himalayas earlier than P. petaurista albiventer, and may have had a longer evolutionary period to adapt to the cool mesic climate of this region.

The NADH Dehydrogenase Genes of Apis mellifera, A. cerana, A. dorsata, A. laboriosa and A. florea: Sequence Comparison and Genetic Diversity

The genetic analysis of mitochondrial DNA (mtDNA) provides substantial information for evolutionary studies. A relatively small size compared with nuclear DNA, a rapid rate of sequence divergence, and maternal inheritance, make the mtDNA a useful tool for molecular phylogenetic studies. Here, we investigated and analyzed the mtDNA of five species of honeybees, Apis mellifera, A. cerana, A. dorsata, A. laboriosa and A. florea collected from Japan, Nepal, and India. A 528-bp DNA fragment of the NADH dehydrogenase subunit 4 (ND4 according to A. mellifera's mt DNA sequence) was PCR-amplified and sequenced. The DNA and deduced amino acid sequences were aligned and the phylogenetic relationships were investigated. The results indicate the genetic diversity of this functional protein among different honeybee species. For these studied species, a high A+T content (from 78.21 to 79.74%) was observed. Of the three colon positions, the third and the second positions show the most AT bias (91.93%) and the least AT bias (69.66%), respectively. The extremely high A+T content in the gene leads to high A → T and T → A transversion substitutions and the biases of colon usage. The phylogenetic trees were constructed with maximum likelihood method for the amino acid and the nucleotide sequences of ND4. For the analysis of nucleotide sequences, the first and second positions and the third position of the colons were separately investigated. All trees showed that evolutionary relationship between A. mellifera and A. cerana was close as well as between A. dorsata and A. laboriosa, while the phylogenetic position of A. florea was uncertain.

Imprint of somatic hypermutation differs in human immunoglobulin heavy and lambda chain variable gene segments

Somatic hypermutation (SHM) introduces mutations into immunoglobulin (Ig) variable gene segments, thus diversifying the B cell repertoire prior to positive selection of high affinity variants during maturation of T cell-dependent B cell responses. Somatic hypermutation of Ig heavy chain generates predominantly single base substitutions, favoring transition rather than transversion substitutions, and tends to direct mutations to specific 4-mer target sequences with G in second and C in third position. Here we have analyzed heavily mutated, nonproductively rearranged Ig lambda chain variable gene segments from human intestinal plasma cells, controlling for germline composition of the genes and local sequence variability. We have observed significant G·C strand bias in IgV λ, and differences in some di- and trinuleotide target preferences in IgV λ compared to IgV H. There is also a significant tendency to accumulate adjacent triplet mutations in IgV λ, which is not evident in IgV H in normal circumstances. These observations suggest that some aspect of the mechanism of somatic hypermutation operates differently in human immunoglobulin heavy and lambda light chain variable gene segments.