Codon Positions Research Articles

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania

BackgroundThe World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance.MethodsEligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440–600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively.ResultsOf 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene.ConclusionThe study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies.Trial Registration ClinicalTrials.gov NCT03387631

Exon prediction based on multiscale products of a genomic-inspired multiscale bilateral filtering.

Multiscale signal processing techniques such as wavelet filtering have proved to be particularly successful in predicting exon sequences. Traditional wavelet predictor is domain filtering, and enforces exon features by weighting nucleotide values with coefficients. Such a measure performs linear filtering and is not suitable for preserving the short coding exons and the exon-intron boundaries. This paper describes a prediction framework that is capable of non-linearly processing DNA sequences while achieving high prediction rates. There are two key contributions. The first is the introduction of a genomic-inspired multiscale bilateral filtering (MSBF) which exploits both weighting coefficients in the spatial domain and nucleotide similarity in the range. Similarly to wavelet transform, the MSBF is also defined as a weighted sum of nucleotides. The difference is that the MSBF takes into account the variation of nucleotides at a specific codon position. The second contribution is the exploitation of inter-scale correlation in MSBF domain to find the inter-scale dependency on the differences between the exon signal and the background noise. This favourite property is used to sharp the important structures while weakening noise. Three benchmark data sets have been used in the evaluation of considered methods. By comparison with four existing techniques, the prediction results demonstrate that: the proposed method reveals at least improvement of 4.1%, 50.5%, 25.6%, 2.5%, 10.8%, 15.5%, 11.1%, 12.3%, 9.2% and 2.4% on the exons length of 1–24, 25–49, 50–74, 75–99, 100–124, 125–149, 150–174, 175–199, 200–299 and 300–300+, respectively. The MSBF of its nonlinear nature is good at energy compaction, which makes it capable of locating the sharp variations around short exons. The direct scale multiplication of coefficients at several adjacent scales obviously enhanced exon features while the noise contents were suppressed. We show that the non-linear nature and correlation-based property achieved in proposed predictor is greater than that for traditional filtering, which leads to better exon prediction performance. There are some possible applications of this predictor. Its good localization and protection of sharp variations will make the predictor be suitable to perform fault diagnosis of aero-engine.

The influence of different types of translational inaccuracies on the genetic code structure

BackgroundThe standard genetic code is a recipe for assigning unambiguously 21 labels, i.e. amino acids and stop translation signal, to 64 codons. However, at early stages of the translational machinery development, the codons did not have to be read unambiguously and the early genetic codes could have contained some ambiguous assignments of codons to amino acids. Therefore, the goal of this work was to obtain the genetic code structures which could have evolved assuming different types of inaccuracy of the translational machinery starting from unambiguous assignments of codons to amino acids.ResultsWe developed a theoretical model assuming that the level of uncertainty of codon assignments can gradually decrease during the simulations. Since it is postulated that the standard code has evolved to be robust against point mutations and mistranslations, we developed three simulation scenarios assuming that such errors can influence one, two or three codon positions. The simulated codes were selected using the evolutionary algorithm methodology to decrease coding ambiguity and increase their robustness against mistranslation.ConclusionsThe results indicate that the typical codon block structure of the genetic code could have evolved to decrease the ambiguity of amino acid to codon assignments and to increase the fidelity of reading the genetic information. However, the robustness to errors was not the decisive factor that influenced the genetic code evolution because it is possible to find theoretical codes that minimize the reading errors better than the standard genetic code.

The codon usage pattern of genes involved in ovarian cancer.

In this study, we analyzed the compositional dynamics and codon usage pattern of genes involved in ovarian cancer (OC) using a computational method. Mutations in specific genes are associated with OC, and some genes are risk factors for progression of OC, but no work has been reported yet on the codon usage pattern of genes involved in OC. Nucleotide composition analysis of OC-related genes suggested that the overall GC content was higher than AT content; that is, the genes were GC rich. The improved effective number of codons indicated that the overall extent of codon usage bias of genes involved in OC was low. The codons AGC, CTG, ATC, ACC, GTG, and GCC were overrepresented, while the codons TCG, TTA, CTA, CCG, CAA, CGT, ATA, ACG, GTA, GTT, GCG, and GGT were underrepresented in the genes. Correspondence analysis suggested that the codon usage pattern was different in different genes. A highly significant correlation was observed between GC12 and GC3 (r = 0.587, P < 0.01) of genes, suggesting that directional mutation affected the three codon positions. Our report on the codon usage pattern of genes involved in OC includes a new perspective for elucidating the mechanisms of biased usage of synonymous codons, as well as providing useful clues for molecular genetic engineering.

A precedented nuclear genetic code with all three termination codons reassigned as sense codons in the syndinean Amoebophrya sp. ex Karlodinium veneficum.

Amoebophrya is part of an enigmatic, diverse, and ubiquitous marine alveolate lineage known almost entirely from anonymous environmental sequencing. Two cultured Amoebophrya strains grown on core dinoflagellate hosts were used for transcriptome sequencing. BLASTx using different genetic codes suggests that Amoebophyra sp. ex Karlodinium veneficum uses the three typical stop codons (UAA, UAG, and UGA) to encode amino acids. When UAA and UAG are translated as glutamine about half of the alignments have better BLASTx scores, and when UGA is translated as tryptophan one fifth have better scores. However, the sole stop codon appears to be UGA based on conserved genes, suggesting contingent translation of UGA. Neither host sequences, nor sequences from the second strain, Amoebophrya sp. ex Akashiwo sanguinea had similar results in BLASTx searches. A genome survey of Amoebophyra sp. ex K. veneficum showed no evidence for transcript editing aside from mitochondrial transcripts. The dynein heavy chain (DHC) gene family was surveyed and of 14 transcripts only two did not use UAA, UAG, or UGA in a coding context. Overall the transcriptome displayed strong bias for A or U in third codon positions, while the tRNA genome survey showed bias against codons ending in U, particularly for amino acids with two codons ending in either C or U. Together these clues suggest contingent translation mechanisms in Amoebophyra sp. ex K. veneficum and a phylogenetically distinct instance of genetic code modification.

Haplotype diversity in medically important red scorpion (Scorpiones: Buthidae: Hottentotta tamulus) from India

The medically important Indian red scorpion, Hottentotta tamulus, is one of the most poisonous scorpions of Indian subcontinent. We studied the haplotype diversity in eight populations of H. tamulus based on mitochondrial cytochrome oxidase subunit I (COI) partial gene sequence. Analyses revealed 22 haplotypes with a haplotype diversity of 0.941 and nucleotide diversity of 0.023. For the first two codon positions both transition and transversion types of substitutions were equally likely and the test for neutrality was not rejected. However, codon substitution pattern indicated that the gene has experienced purifying selection. Model-based clustering method indicated that the eight populations form three groups that correspond to high, moderate and low rainfall areas, indicating that there is biogeographical separation of haplotypes. Populations from three groups formed distinct clades in maximum likelihood analysis and median joining genetic network and were statistically supported by low within group and high among group variation in analyses of molecular variance. We provide the first account of haplotype diversity in Indian red scorpions and their biogeographical separation.

Abstract P3-06-06: Novel breast cancer mutational signatures

Abstract Background: Our understanding of the biological processes that generate somatic mutations in breast cancer has increased markedly over the past five years. Using the catalog of somatic mutations present in cancer genomes, over 30 “mutational signatures” have been produced. While these provide important insights into the processes responsible for somatic mutation, gaps remain, and the etiology of several signatures remains unknown. Methods: We have developed a new method in which the specific nucleotide change (e.g., C&amp;gt;T), the codon that each mutation falls in (e.g., GCT), the position in the codon (e.g., 2), and the nucleotides immediately 5' and 3' of the mutation (e.g., 5': C; 3': G) are all considered. The summary of these mutation characteristics forms a mutational profile for each tissue sample. Putting multiple samples' profiles together forms a sparse matrix with the number of samples as rows and the mutation characteristics as columns. Nonsmooth nonnegative matrix factorization was then applied to enable the discovery of intrinsic patterns in this sparse matrix. Results: Using somatic mutations identified in 1017 breast cancer tissues from The Cancer Genome Atlas (TCGA), we have identified four mutational signatures. Signature A correlates with the well-defined APOBEC signatures and signature B with the “aging” signature, which is the result 5-methylcytosine hydrolysis. Signature C and signature D are potentially new signatures. Signature D is enriched with C:G&amp;gt;A:T mutations; these mostly occur in the middle position of codons, and are enriched with GG(CC) either 5' or 3' of the mutation's sequence context. G&amp;gt;T mutations are known to occur as a consequence of oxidative damage that is not repaired. Guanines are vulnerable as they have the highest vertical oxidation potential of the nucleobases. The 5' guanines in GG sites are especially reactive. We hypothesize that Signature D results from oxidative mutagenesis. When correlated with clinical phenotypes, the basal subtype is clearly enriched for tumors with the Signature D mutation pattern (exposure level is in 169 basal tumors and in 797 non-basal tumors, p=&amp;lt;0.01), suggesting an etiologic link with basal-like breast cancer. G&amp;gt;T somatic mutations in breast cancer mainly take place during cell replication rather than during transcription. In the normal breast, epithelial cell replication occurs during the luteal phase of the menstrual cycle and during pregnancy, primarily under the direction of progesterone (P). P binds to its receptor (PR) in a subpopulation of PR positive cells where it initiates the transcription of genes including RANKL, with resultant paracrine stimulation (through RANK), of the NF-κB signaling pathway in neighboring cells. The four RANKL genes (TOP2A, MKI67, PBK, CDK1), defined by Nolan et al., are all positively associated with the signature D (P-values &amp;lt; 0.05), suggesting that this type of mutagenesis is associated with RANKL pathway upregulation. Conclusions: We have identified a potentially new somatic mutational signature, which we have designated as Signature D, which appears to result from exposure of DNA to oxidative stress during replication. It is associated with the basal subtype of breast cancer as well as RANKL- NF-κB pathway upregulation. Citation Format: Zeng Z, Vo AH, Luo Y, Khan SA, Clare SE. Novel breast cancer mutational signatures [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-06.

TA, GT and AC are significantly under-represented in open reading frames of prokaryotic and eukaryotic protein-coding genes.

Genomes can be considered a combination of 16 dinucleotides. Analysing the relative abundance of different dinucleotides may reveal important features of genome evolution. In present study, we conducted extensive surveys on the relative abundances of dinucleotides in various genomic components of 28 bacterial, 20 archaean, 19 fungal, 24 plant and 29 animal species. We found that TA, GT and AC are significantly under-represented in open reading frames of all organisms and in intergenic regions and introns of most organisms. Specific dinucleotides are of greatly varied usage at different codon positions. The significantly low representations of TA, GT and AC are considered the evolutionary consequences of preventing formation of pre-mature stop codons and of reducing intron-splicing options in candidate primary mRNA sequences. These data suggest that a reduction of TA and GT occurred on both strands of the DNA sequence at an early stage of de novo gene birth. Interestingly, GT and AC are also significantly under-represented in current prokaryotic genomes, suggesting that ancient prokaryotic protein-coding genes might have contained introns. The greatly varied usages of specific dinucleotides at different codon positions are considered evolutionary accommodations to compensate the unavailability of specific codons and to avoid formation of pre-mature stop codons. This is the first report presenting data of dinucleotide relative abundance to indicate the possible existence of spliceosomal introns in ancient prokaryotic genes and to hypothesize early steps of de novo gene birth.

Analysis of codon usage patterns and influencing factors in Nipah virus

Codon usage bias (CUB) is the unequal usage of synonymous codons of an amino acid in which some codons are used more often than others and is widely used in understanding molecular biology, genetics, and functional regulation of gene expression. Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes fatal disease in both humans and animals. NiV was first identified during an outbreak of a disease in Malaysia in 1998 and then occurred periodically since 2001 in India, Bangladesh, and the Philippines. We used bioinformatics tools to analyze the codon usage patterns in a genome-wide manner among 11 genomes of NiV as no work was reported yet. The compositional properties revealed that the overall GC and AT contents were 41.96 and 58.04%, respectively i.e. Nipah virus genes were AT-rich. Correlation analysis between overall nucleotide composition and its 3rd codon position suggested that both mutation pressure and natural selection might influence the CUB across Nipah genomes. Neutrality plot revealed natural selection might have played a major role while mutation pressure had a minor role in shaping the codon usage bias in NiV genomes.

Species specificity and host affinity rather than tissue tropism controls codon usage pattern in respiratory mycoplasmosis

Respiratory Mycoplasmosis (rMyc) is a devastating respiratory disease causing serious pneumonia in camels, cattle and human causing fatalities and high economic loss. Codon usage pattern is an important measure of host-parasite relationship, parasites adaptation and evolution. In this work, two important species of rMyc affecting human (Mycoplasma pneumoniae) and camels (Mycoplasma mycoides) were analysed for finding their codon usage bias, factors affecting their genomes composition and their relation to their host including adaptation and disease pathogenesis. In spite of their reduced genome size, rMyc showed comprehensive and host-independent codon usage machinery with wide variability and incompatibility with their host pattern. Although, rMyc are common infectious agents of respiratory tract, they showed completely diverse codon usage, adaptation and pathogenesis profiles. M. mycoides showed strict highly biased A/T selection in their genomic composition, preferred codons and at the 3rd position of codons as well as highly divergent codon usage pattern compared with its host. M. pneumoniae showed more attempts in adaptation to mammalian host environment by showing codon usage pattern almost similar to their host. High GC content in genome, low number of overbiased and underbiased codons, high ENc values and balanced use of GC and AT in preferred codons N3s were among the factors of adaptation to its habitat. There was immune selection among rMyc. M. mycoides is more immune resistant by showing lower CpG dinucleotide frequency compared with M. pneumoniae. The higher and faster gene expression in M. mycoides, and to a lesser extent M. pneumoniae, devoted from low ENc values accounts for high pathogenicity and acute disease. Common evolutionary origin and variable codon usage indices account for variable attempts among Mycoplasma species to adapt their habitat regardless their tissue tropism or host specificity.

Tumor suppressor p53 gene codon 72 polymorphism and imatinib cytogenetic response in chronic myeloid leukemia

Objective To study p53 codon 72 polymorphism in relation to cytogenetic response to imatinib treatment in patients with chronic myeloid leukemia (CML). Background P53 polymorphism involves the substitution of an arginine for a proline at codon position 72. Many studies have investigated a genetic link between this variation and response to treatment in cancer. Patients and methods This study was conducted on 54 CML patients presented to the Clinical Oncology Department, Menoufia University during the period from June 2013 to April 2015. They were classified according to their cytogenetic response to imatinib therapy into 40 CML patients, cytogenetic responders to imatinib and 14 CML patients who are cytogenetic nonresponders to imatinib. Patients were genotyped for p53 codon 72 polymorphism using PCR. Follow up of the patients should be done after 3, 6, 9, 12, and 18 months after diagnosis, and was done by complete blood count, conventional cytogenetic, and fluorescence in-situ hybridization. Results Age, sex, hematologic, and cytogenetic response to imatinib in CML patients did not differ significantly among p53 codon 72 genotypes (arg/arg, arg/pro, and pro/pro) (P = 0.44, P = 0.45, and P = 0.11, respectively). P53 codon 72 polymorphism did not significantly alter the risk to imatinib cytogenetic unresponsiveness (P = 0.9221). Conclusion It could be concluded that p53 codon 72 polymorphism is not associated with imatinib unresponsiveness in CML.

Nonsense Suppression Position Effect Implicates Poly(A)-Binding Protein in the Regulation of Translation Termination

Readthrough of translation termination codons, also known as nonsense suppression, is a relatively inefficient process mediated by ribosomal A site recognition and insertion of near-cognate tRNAs. Multiple factors influence readthrough efficiency, including nonsense codon specificity and context. To determine whether nonsense codon position in a gene influences the extent of readthrough, we generated a series of LUC nonsense alleles and quantitated both readthrough and termination efficiencies at each nonsense codon in yeast cells lacking nonsense-mediated mRNA decay (NMD) activity. Readthrough efficiency for premature termination codons (PTCs) manifested a marked dependence on PTC proximity to the mRNA 3’-end, decreasing progressively across the LUC ORF but increasing with 3’-UTR lengthening. These effects were eliminated, and translation termination efficiency decreased considerably, in cells harboring pab1 mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and suggest that inefficient termination is the trigger for NMD.

Analysis of codon usage bias in the VP1 gene of the human norovirus GII.2 genotype

To investigate the codon usage patterns of all available VP1 gene sequences of the GII.2 genotype, to determine the factors that affect these patterns, and to provide comprehensive details of the characteristics and evolution of the gene. Complete 519 sequences of VP1 gene of the HuNoV GII.2 genotype with known sampling dates and geographic locations from 1971 - 2017 were retrieved from the GenBank nucleotide database of the National Center for Biotechnology Information (NCBI) and analyzed. The percentage composition of T, C, A, and G nucleotides were 24.80 ± 0.30, 26.61 ± 0.31, 25.84 ± 0.13, and 22.75 ± 0.17 %, respectively, with C and A relatively more abundant than T and G, and C the most abundant (p &lt; 0.0001). The values of T3s (34.10 ± 0.90 %) and C3s (33.54 ± 0.90 %) were significantly higher than those of A3s (29.98 ± 0.43 %) and G3s (24.13 ± 0.51 %) (p &lt; 0.0001). While T3s was highest among the four nucleotides, G3s was the lowest. Among the 18 most frequently employed synonymous codons, six optional codons ended with T, five ended with C, five ended with A and two ended with G. Codons ending with T were the most frequently used. The ENC ranged from 51.90 to 54.25 (mean = 52.38 ± 0.43) among the 519 VP1 gene sequences. There were significant correlations between ENC and C % and G % (p &lt; 0.01). Codons containing CpG (1 and 2 or 2 and 3 codon positions) showed the lowest frequencies, while 30, 29, and 2 codons were above, below and on the mean line, respectively. The first four principal components accounted for 69.11 % of the total variation, with the first, second, third, and fourth principal axes contributing 37.90, 14.83, 9.61, and 6.77 %, respectively. The strains were not clustered by country of isolation or year of sampling. Gravy were significantly correlated with T3s, C3s, G3s, GC3s, and ENC (p &lt; 0.01). Mutation pressure and natural selection contributed to the codon usage bias of the VP1 gene of the HuNoV GII.2 genotype. There was a correlation between GC12s and GC3s (R2 = 0.032; p &lt; 0.0001). The relative neutrality was 3.20 %, while natural selection was 96.80 %. The VP1 gene exhibits low codon usage bias which is affected primarily by natural selection, followed by mutation pressure and translational selection.

A cross-talk on compositional dynamics and codon usage patterns of mitochondrial CYB gene in Echinodermata

Codon usage bias (CUB) refers to a phenomenon in which some synonymous codons are used in mature mRNA at a higher frequency than other members codifying the same amino acid. CUB is mainly determined by mutation pressure and natural selection. We used bioinformatic tools to analyze the protein coding sequences of mitochondrial CYB gene in different classes of Echinodermata to understand the patterns of codon usage. The ENC values of CYB gene in five different classes of Echinodermata were 41.64, 30.33, 43.63, 41.11, and 41.33, which suggested that the CUB of this gene was low. The relative synonymous codon usage (RSCU) values showed that the patterns of over-represented and under-represented codons were different among different classes. Correspondence analysis indicated that the plots of CYB gene were different across classes, suggesting that the pattern of codon usage was also different among five classes under study. Highly significant correlation (p < .01) between overall nucleotide composition and its 3rd codon position indicated that both mutational pressure and natural selection had an influence on the codon usage bias of CYB gene. Furthermore, PR-2 bias plot analysis showed that both mutation pressure and natural selection might have affected the pattern of codon usage in CYB gene of Echinodermata.

Comparative analysis of seven mitochondrial genomes of Phymatostetha (Hemiptera: Cercopidae) and phylogenetic implications

In this study, we present seven mitochondrial genomes (mitogenomes) of Phymatostetha. Each mitogenome contains the entire set of 37 genes, which arranged in the same order as the putative ancestral pattern of insects. The nucleotide composition of Phymatostetha mitogenomes is biased toward A/T, with rRNAs and PCG12 (i.e. the first and second codon positions of PCGs) exhibit the highest and lowest A + T content, respectively. Relative synonymous codon usage of PCGs also show that degenerate codons are biased to use more A/T than G/C. All tRNAs exhibit typical clover-leaf structure, with the exception of trnS1. Additionally, unpaired nucleotides are detected in trnS1 anticodon stem and trnR acceptor stem. Phylogenetic relationships, based on the dataset of 13 PCGs, 22tRNAs, and two rRNAs, are analyzed using both the Bayesian and maximum likelihood methods. Our results clearly revealed the systematic status of Phymatostetha species and robustly supported the monophyly of this genus, in which Phymatostetha semele is sister to other Phymatostetha species. It was demonstrated that mitogenome was an effective molecular marker to adequately resolve phylogeny at low taxonomic levels.

Abundant Small Genetic Alterations after Upland Cotton Domestication.

Domestication has long been recognized as the most direct and effective way to intentionally influence morphological and physiological phenotypes in plants and animals. Consequently, understanding how small genetic alterations contribute to domestication is of considerable importance. In this study, we resequenced the genome of the wild upland cotton variety Gossypium hirsutum var. yucatanense, the putative wild ancestor of cultivated upland cotton, and then compared single nucleotide polymorphism (SNP) and short insertion and deletion (InDel) variations of the genome with the cultivated accession (TM-1) of G. hirsutum. We found approximately 6.6 million SNPs and 0.7 million InDels between the two genomes. Most of the small genetic variations were anchored in the noncoding regions. With regard to potential coding genes, we found 24,035 genes with nonsynonymous SNPs. Interestingly, 2603 genes in domesticated cotton are found that have changed the positions of stop codons or shifted reading frames from that in G. hirsutum var. yucatanense. This suggests that domestication may have been selected for mutations that restored gene function or that wild cotton has undergone a number of gene inactivation events since its divergence from cultivated cotton. The former scenario seems most likely due to the intense selective pressure applied during the domestication process. These results demonstrate that, within a relatively short period of time, the cotton genome has been readjusted through small genetic changes. The current study provides useful clues for seeking interesting genes for cotton improvement.

N4-acetylation of Cytidine in mRNA by NAT10 Regulates Stability and Translation

Arango etal. expand the repertoire of epitranscriptomic modifications by identifying N4-acetylcytidine in mRNA catalyzed by the known dual acetyltransferase NAT10. It occurs mainly in the coding sequence, likely in wobble positions of select codons, where it promotes stability and translation, possibly by safeguarding cognate codon-anticodon interaction.

Duplicated Myosin V Genes in Teleosts Show Evolutionary Rate Variations among the Motor and Cargo-Binding Domains.

We analyzed evolutionary rates of conserved, duplicated myosin V (myo5) genes in nine teleost species to examine the outcomes of duplication events. Syntenic analysis and ancestral chromosome mapping suggest one tandem gene duplication event leading to the appearance of myo5a and myo5c, two rounds of whole genome duplication for vertebrates, and an additional round of whole genome duplication for teleosts account for the presence and location of the myo5 genes and their duplicates in teleosts and other vertebrates and the timing of the duplication events. Phylogenetic analyses reveal a previously unidentified myo5 clade that we refer to now as myo5bb. Analysis using dN/dS rate comparisons revealed large regions within duplicated myo5 genes that are highly conserved. Codons identified in other studies as encoding functionally important portions of the Myo5a and Myo5b proteins are shown to be highly conserved within the newly identified myo5bb clade and in other myo5 duplicates. As much as 30% of 319 codons encoding the cargo-binding domain in the myo5aa genes are conserved in all three codon positions in nine teleost species. For the myo5bb cargo-binding domain, 6.6% of 336 codons have zero substitutions in all nine teleost species. Using molecular evolution assays, we identify the myo5bb branch as being subject to evolutionary rate variation with the cargo-binding domain, having 20% of the sites under positive selection and the motor domain having 8% of its sites under positive selection. The high number of invariant codons coupled with relatively high dN/dS values in the region of the myo5 genes encoding the ATP-binding domain suggests the encoded proteins retain function and may have acquired novel functions associated with changes to the cargo-binding domain.

Historical biogeography of the termite clade Rhinotermitinae (Blattodea: Isoptera)

Termites are the principal decomposers in tropical and subtropical ecosystems around the world. Time-calibrated molecular phylogenies show that some lineages of Neoisoptera diversified during the Oligocene and Miocene, and acquired their pantropical distribution through transoceanic dispersal events, probably by rafting in wood. In this paper, we intend to resolve the historical biogeography of one of the earliest branching lineages of Neoisoptera, the Rhinotermitinae. We used the mitochondrial genomes of 27 species of Rhinotermitinae to build two robust time-calibrated phylogenetic trees that we used to reconstruct the ancestral distribution of the group. Our analyses support the monophyly of Rhinotermitinae and all genera of Rhinotermitinae. Our molecular clock trees provided time estimations that diverged by up to 15.6 million years depending on whether or not 3rd codon positions were included. Rhinotermitinae arose 50.4–64.6 Ma (41.7–74.5 Ma 95% HPD). We detected four disjunctions among biogeographic realms, the earliest of which occurred 41.0–56.6 Ma (33.0–65.8 Ma 95% HPD), and the latest of which occurred 20.3–34.2 Ma (15.9–40.4 Ma 95% HPD). These results show that the Rhinotermitinae acquired their distribution through a combination of transoceanic dispersals and dispersals across land bridges.

Evolutionary Divergence of CXCR1 (Interleukin-8 Receptor A) Gene of Indian Water Buffalo (Bubalus bubalis) in Light of Molecular Evolution

CXCR1 (Interleukin-8 Receptor A) is one of the two high-affinity receptors (IL-8RA and IL-8RB), present on the surface of neutrophils that binds to the IL-8 ligand, which results in the activation of immune response and allows the migration of immune cells to the site of inflammation. CXCR1 is strongly associated with inflammatory responses against most of the Gram-negative bacteria. The objective of the present work was to amplify, sequence and in silico characterize CXCR1 coding region of buffalo. The amplified target gene of buffalo CXCR1 was custom-sequenced, and the annotated sequence of 1130 bp having coding region of 1083 bp was submitted to DDBJ with accession number LC384988. Pairwise sequence alignment of buffalo CXCR1 and the reference cattle CXCR1 showed 95% similarity. Sequence analysis and integrative analysis of CXCR1 in 36 divergent species revealed that 7 codon positions have undergone positive selection pressure, indicating that the gene has undergone evolutionary changes over the period of time. Evolutionary analysis of the CXCR1 (MEGA 6 and Datamonkey online server) revealed that ruminant, avian, fish CXCR1 formed different clusters within the phylogenetic tree, showing evolutionary divergence.