Nonsynonymous Nucleotide Substitutions Research Articles

The novel HLA-DRB1*11:323 allele characterized by two different sequencing-based typing techniques.

The novel allele HLA-DRB1*11:323 differs from HLA-DRB1*11:01:02:01 by one non-synonymous nucleotide substitution in exon 2.

The novel HLA-DPB1*1467:01 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-DPB1*1467:01 differs from HLA-DPB1*09:01:01:01 by one non-synonymous nucleotide substitution in exon 2.

The novel HLA-A*36:14 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-A*36:14 differs from HLA-A*36:01:01:01 by one non-synonymous nucleotide substitution in exon 4.

The novel HLA-DRB1*03:210 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-DRB1*03:210 differs from HLA-DRB1*03:01:01:01 by one non-synonymous nucleotide substitution in exon 3.

Evidence for Selection on Mitochondrial OXPHOS Genes in the Mediterranean Killifish Aphanius fasciatus Valenciennes, 1821.

Mitochondrial oxidative phosphorylation (OXPHOS) genes are a system subject to selection under determined environmental constraints despite a neutral evolution model that has long been hypothesized for the mitochondrial genome. In this study, the sequences of ND1, Cytb, and COI OXPHOS genes were analyzed in six populations of the eurythermal and euryhaline killifish A. fasciatus, to detect non-synonymous mutations leading to amino acid changes and to check whether selection acted on them using tests of recombination and selection. The results indicate a high COI and Cytb gene diversity and a high percentage of private haplotypes in all populations. In the Greek population, non-synonymous nucleotide substitutions were observed in the N-terminal region of COI and Cytb. Positively selected sites were also found. The information we obtained from the mitochondrial DNA sequences of A. fasciatus adds to the growing data on selective pressure acting on mitochondrial DNA in non-model species. These results should be explored from the perspective of the local adaptation of eurythermal and euryhaline species and supported using experimental evidence to better understand the interplay between historical climatic events and local adaptation and how each of them contributes to shaping the genetic structure of this species.

Genomic full-length sequence of the novel HLA-B*56:94 allele.

HLA-B*56:94 differs from HLA-B*56:05:01 by two non-synonymous nucleotide substitutions in exon 1 and synonymous nucleotide substitutions in exon 1 and exon 2.

Next-generation sequencing identifies two novel HLA-DPB1 alleles: HLA-DPB1*1069:01 and DPB1*1072:01.

Characterization of two novel HLA-DPB1 alleles: HLA-DPB1*1069:01, and DPB1*1072:01 containing non-synonymous nucleotide substitutions.

Genomic full-length sequence of the novel HLA-A*02:1100 allele.

HLA-A*02:1100 differs from HLA-A*02:01:01:01 by a single non-synonymous nucleotide substitution in codon 76 of exon 2.

Genome reduction occurred in early Prochlorococcus with an unusually low effective population size.

In the oligotrophic sunlit ocean, the most abundant free-living planktonic bacterial lineages evolve convergently through genome reduction. The cyanobacterium Prochlorococcus responsible for 10% global oxygen production is a prominent example. The dominant theory known as "genome streamlining" posits that they have extremely large effective population sizes (Ne) such that selection for metabolic efficiency acts to drive genome reduction. Because genome reduction largely took place anciently, this theory builds on the assumption that their ancestors' Ne was similarly large. Constraining Ne for ancient ancestors is challenging because experimental measurements of extinct organisms are impossible and alternatively reconstructing ancestral Ne with phylogenetic models gives large uncertainties. Here, we develop a new strategy that leverages agent-based modeling to simulate the changes in the genome-wide ratio of radical to conservative nonsynonymous nucleotide substitution rate (dR/dC) in a possible range of Ne in ancestral populations. This proxy shows expected increases with decreases of Ne only when Ne falls to about 10k - 100k or lower, magnitudes characteristic of Ne of obligate endosymbiont species where drift drives genome reduction. Our simulations therefore strongly support a scenario where the primary force of Prochlorococcus genome reduction is drift rather than selection.

Discovery of the HLA-DQB1*06:465 allele, a variant of HLA-DQB1*06:04:01:01.

HLA-DQB1*06:465 differs from HLA-DQB1*06:04:01:01 by a non-synonymous nucleotide substitution in codon 38.

Identification of the novel HLA-A*11:456 allele by next-generation sequencing.

HLA-A*11:456 has one non-synonymous nucleotide substitution compared to HLA-A*11:02:01:01 at position 565 in exon 3.

Nonsynonymous Single Nucleotide Substitutions and Indels: Contribution to the Molecular Postgenome Portrait of the HepG2 Cell Line

Nonsynonymous Single Nucleotide Substitutions and Indels: Contribution to the Molecular Postgenome Portrait of the HepG2 Cell Line

The novel HLA-C*07:1058 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-C*07:1058 differs from HLA-C*07:02:01:01 by one non-synonymous nucleotide substitution in exon 4.

The combined effect of oseltamivir and favipiravir on influenza A virus evolution in patients hospitalized with severe influenza

Our previous study shows favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, but its effect on virological evolution and resistance mutation against oseltamivir is still unknown. In this study, we collected longitudinal respiratory samples from influenza patients who underwent combination therapy and applied them to next generation sequencing of the whole genome of the influenza A virus (IAV). We also included a cohort untreated with any antivirals to serve as the control. In total, 62 samples from 19 patients treated with combination therapy and 20 samples from 20 patients untreated were successfully sequenced. The nucleotide diversity in the whole genome of IAV in the combination group showed no difference compared to that in the control group (P > 0.05). Moreover, we observed 174 kinds of nonsynonymous nucleotide substitutions in patients with combination therapy, mostly in NA (n = 44) and HA (n = 43). Of them, the G→A transition was the dominant variant type (27%) and 46/174 (26%) was reported to have biological effects, such as increased pathogenicity and polymerase activity. Among the 29 mutations conferring reduction in oseltamivir sensitivity we investigated, H275Y was the only mutation detected in the 4 samples from 1 of 19 patients and demonstrated increasing frequency during the treatment. Mutations conferring favipiravir resistance were not observed. Our studies showed combination therapy of favipiravir and oseltamivir has little effect on virus nucleotide diversity, nor prevents the increase of oseltamivir-resistant variants.

The novel HLA-B*44:369 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-B*44:369 differs from HLA-B*44:02:01:01 by one non-synonymous nucleotide substitution in exon 3.

A homozygous missense mutation in the fibroblast growth factor 5 gene is associated with the long-hair trait in Angora rabbits

BackgroundRabbits are well-domesticated animals. As a crucial economic animal, rabbit has been successfully bred into wool-use, meat-use and fur-use breeds. Hair length is one of the most economically important traits affecting profitability in wool rabbits. In this study, to identify selection signatures with the long-hair trait, whole-genomic resequencing of long-haired rabbits (Angora rabbits) and short-haired rabbits (Rex and New Zealand rabbits) was performed.ResultsBy genome-wide selective sweeping analysis based on population comparison, we identified a total of 5.85 Mb regions (containing 174 candidate genes) with strong selection signals. Six of these genes (Dusp1, Ihh, Fam134a, Map3k1, Spata16, and Fgf5) were enriched in the MAPK signalling and Hedgehog signalling pathways, both of which are closely associated with hair growth regulation. Among these genes, Fgf5 encodes the FGF5 protein, which is a well-established regulator of hair growth. There was a nonsynonymous nucleotide substitution (T19234C) in the Fgf5 gene. At this locus, the C allele was present in all of the tested Angora rabbits, while the T allele was dominant in New Zealand and Rex rabbits. We further confirmed that the C allele was conserved in Angora rabbits by screening an additional 135 rabbits. Moreover, the results of functional predictions and co-immunoprecipitation revealed that the T19234C mutation impaired the binding capacity of FGF5 to its receptor FGFR1.ConclusionsWe discovered that the homozygous missense mutation T19234C within Fgf5 might contribute to the long-hair trait of Angora rabbits by reducing its receptor binding capacity. This finding will provide new insights into the genetic basis underlying the genetic improvement of Angora rabbits and benefit the improvement of rabbit breeding in the future.

The novel HLA-A*11:443 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-A*11:443 differs from HLA-A*11:01:01:01 by one non-synonymous nucleotide substitution in exon 2.

The novel HLA-B*56:91 allele characterised by three different sequencing-based typing techniques.

The novel allele HLA-B*56:91 differs from HLA-B*56:33 by one non-synonymous nucleotide substitution in exon 2.

The novel HLA-DRB1*16:71 allele characterised by two different sequencing-based typing techniques.

The novel allele HLA-DRB1*16:71 differs from HLA-DRB1*16:01:01:01 by one non-synonymous nucleotide substitution in exon 2.

The novel HLA-DRB5*02:35 allele characterized by two different sequencing-based typing techniques.

The novel allele HLA-DRB5*02:35 differs from HLA-DRB5*02:02:01 by one non-synonymous nucleotide substitution in exon 2.