scholarly journals Large-Scale Analyses of Positive Selection Using Codon Models

2009 ◽  
pp. 217-235 ◽  
Author(s):  
Romain A. Studer ◽  
Marc Robinson-Rechavi
Keyword(s):  
Positive Selection ◽  
Large Scale ◽  
Codon Models

scholarly journals Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection

2017 ◽  
Author(s):  
Iakov I. Davydov ◽  
Nicolas Salamin ◽  
Marc Robinson-Rechavi
Keyword(s):  
Positive Selection ◽  
Mutation Rate ◽  
Substitution Rate ◽  
Large Scale ◽  
Synonymous Substitution ◽  
Rate Variation ◽  
New Model ◽  
Codon Models ◽  
Substitution Rate Variation ◽  
Mutation Rate Variation

AbstractThere are numerous sources of variation in the rate of synonymous substitutions inside genes, such as direct selection on the nucleotide sequence, or mutation rate variation. Yet scans for positive selection rely on codon models which incorporate an assumption of effectively neutral synonymous substitution rate, constant between sites of each gene. Here we perform a large-scale comparison of approaches which incorporate codon substitution rate variation and propose our own simple yet effective modification of existing models. We find strong effects of substitution rate variation on positive selection inference. More than 70% of the genes detected by the classical branch-site model are presumably false positives caused by the incorrect assumption of uniform synonymous substitution rate. We propose a new model which is strongly favored by the data while remaining computationally tractable. With the new model we can capture signatures of nucleotide level selection acting on translation initiation and on splicing sites within the coding region. Finally, we show that rate variation is highest in the highly recombining regions, and we propose that recombination and mutation rate variation, such as high CpG mutation rate, are the two main sources of nucleotide rate variation. While we detect fewer genes under positive selection in Drosophila than without rate variation, the genes which we detect contain a stronger signal of adaptation of dynein, which could be associated with Wolbachia infection. We provide software to perform positive selection analysis using the new model.

scholarly journals Out of the blue: adaptive visual pigment evolution accompanies Amazon invasion

2015 ◽  
Vol 11 (7) ◽  
pp. 20150349 ◽  
Author(s):  
Alexander Van Nynatten ◽  
Devin Bloom ◽  
Belinda S. W. Chang ◽  
Nathan R. Lovejoy
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Visual Pigment ◽  
Large Scale ◽  
Marine Species ◽  
South American ◽  
Sequence Analyses ◽  
Freshwater Habitats ◽  
Varying Environments ◽  
Visual Pigment Evolution

Incursions of marine water into South America during the Miocene prompted colonization of freshwater habitats by ancestrally marine species and present a unique opportunity to study the molecular evolution of adaptations to varying environments. Freshwater and marine environments are distinct in both spectra and average intensities of available light. Here, we investigate the molecular evolution of rhodopsin, the photosensitive pigment in the eye that activates in response to light, in a clade of South American freshwater anchovies derived from a marine ancestral lineage. Using likelihood-based comparative sequence analyses, we found evidence for positive selection in the rhodopsin of freshwater anchovy lineages at sites known to be important for aspects of rhodopsin function such as spectral tuning. No evidence was found for positive selection in marine lineages, nor in three other genes not involved in vision. Our results suggest that an increased rate of rhodopsin evolution was driven by diversification into freshwater habitats, thereby constituting a rare example of molecular evolution mirroring large-scale palaeogeographic events.

scholarly journals A shuttle-vector system allows heterologous gene expression in the thermophilic methanogen Methanothermobacter thermautotrophicus ΔH

2021 ◽  
Author(s):  
Christian Fink ◽  
Sebastian Beblawy ◽  
Andreas M. Enkerlin ◽  
Lucas Mühling ◽  
Largus T. Angenent ◽  
...  
Keyword(s):  
Gene Expression ◽  
Positive Selection ◽  
Large Scale ◽  
Heterologous Gene Expression ◽  
Shuttle Vector ◽  
Heterologous Gene ◽  
Vector System ◽  
Physiology And Biochemistry ◽  
Methanothermobacter Thermautotrophicus ◽  
Power To Gas

AbstractThermophilic Methanothermobacter spp. are used as model microbes to study the physiology and biochemistry of the conversion of hydrogen and carbon dioxide into methane (i.e., hydrogenotrophic methanogenesis), because of their short doubling times and robust growth with high growth yields. Yet, a genetic system for these model microbes was missing despite intense work for four decades. Here, we report the establishment of tools for genetic modification of M. thermautotrophicus. We developed the modular Methanothermobacter vector system, which provided shuttle-vector plasmids (pMVS) with exchangeable selectable markers and replicons for both Escherichia coli and M. thermautotrophicus. For M. thermautotrophicus, a thermostable neomycin-resistance cassette served as the selectable marker for positive selection with neomycin, and the cryptic plasmid pME2001 from Methanothermobacter marburgensis served as the replicon. The pMVS-plasmid DNA was transferred from E. coli into M. thermautotrophicus via interdomain conjugation. After the successful validation of DNA transfer and positive selection in M. thermautotrophicus, we demonstrated heterologous gene expression of a thermostable β-galactosidase-encoding gene (bgaB) from Geobacillus stearothermophilus under the expression control of four distinct synthetic and native promoters. In quantitative in-vitro enzyme activity assays, we found significantly different β-galactosidase activity with these distinct promoters. With a formate dehydrogenase operon-encoding shuttle vector, we allowed growth of M. thermautotrophicus on formate as the sole growth substrate, while this was not possible for the empty vector control. These genetic tools provide the basis to investigate hypotheses from four decades of research on the physiology and biochemistry of Methanothermobacter spp. on a genetic level.Significance StatementThe world economies are facing permanently increasing energy demands. At the same time, carbon emissions from fossil sources need to be circumvented to minimize harmful effects from climate change. The power-to-gas platform is utilized to store renewable electric power and decarbonize the natural gas grid. The microbe Methanothermobacter thermautotrophicus is already applied as the industrial biocatalyst for the biological methanation step in large-scale power-to-gas processes. To improve the biocatalyst in a targeted fashion, genetic engineering is required. With our shuttle-vector system for heterologous gene expression in M. thermautotrophicus, we set the cornerstone to engineer the microbe for optimized methane production, but also for production of high-value platform chemicals in power-to-x processes.

scholarly journals The effects of increasing the number of taxa on inferences of molecular convergence

2016 ◽  
Author(s):  
Gregg W.C. Thomas ◽  
Matthew W. Hahn ◽  
Yoonsoo Hahn
Keyword(s):  
Positive Selection ◽  
Sample Size ◽  
Comparative Studies ◽  
Convergent Evolution ◽  
Marine Mammals ◽  
Large Scale ◽  
Marine Species ◽  
Original Analysis ◽  
Insight Into ◽  
Molecular Convergence

AbstractConvergent evolution provides insight into the link between phenotype and genotype. Recently, large-scale comparative studies of convergent evolution have become possible, but researchers are still trying to determine the best way to design these types of analyses. One aspect of molecular convergence studies that has not yet been investigated is how taxonomic sample size affects inferences of molecular convergence. Here we show that increased sample size decreases the amount of inferred molecular convergence associated with the three convergent transitions to a marine environment in mammals. The sampling of more taxa—both with and without the convergent phenotype—reveals that alleles associated only with marine mammals in small datasets are actually more widespread, or are not shared by all marine species. The sampling of more taxa also allows finer resolution of ancestral substitutions, revealing that they are not in fact on lineages leading to solely marine species. We revisit a previous study on marine mammals and find that only 7 of the reported 43 genes with convergent substitutions still show signs of convergence with a larger number of background species. However, 4 of those 7 genes also showed signs of positive selection in the original analysis and may still be good candidates for adaptive convergence. Though our study is framed around the convergence of marine mammals, we expect our conclusions on taxonomic sampling are generalizable to any study of molecular convergence.

scholarly journals The Parallel Molecular Adaptations to the Antarctic Cold Environment in Two Psychrophilic Green Algae

2019 ◽  
Vol 11 (7) ◽  
pp. 1897-1908 ◽  
Author(s):  
Zhenhua Zhang ◽  
Changfeng Qu ◽  
Ru Yao ◽  
Yuan Nie ◽  
Chenjie Xu ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Positive Selection ◽  
Green Algae ◽  
Large Scale ◽  
Extreme Environments ◽  
Photosynthetic Apparatus ◽  
Antioxidant Systems ◽  
Significant Evidence ◽  
The Antarctic ◽  
Molecular Convergence

Abstract Psychrophilic green algae from independent phylogenetic lines thrive in the polar extreme environments, but the hypothesis that their psychrophilic characteristics appeared through parallel routes of molecular evolution remains untested. The recent surge of transcriptome data enables large-scale evolutionary analyses to investigate the genetic basis for the adaptations to the Antarctic extreme environment, and the identification of the selective forces that drive molecular evolution is the foundation to understand the strategies of cold adaptation. Here, we conducted transcriptome sequencing of two Antarctic psychrophilic green algae (Chlamydomonas sp. ICE-L and Tetrabaena socialis) and performed positive selection and convergent substitution analyses to investigate their molecular convergence and adaptive strategies against extreme cold conditions. Our results revealed considerable shared positively selected genes and significant evidence of molecular convergence in two Antarctic psychrophilic algae. Significant evidence of positive selection and convergent substitution were detected in genes associated with photosynthetic machinery, multiple antioxidant systems, and several crucial translation elements in Antarctic psychrophilic algae. Our study reveals that the psychrophilic algae possess more stable photosynthetic apparatus and multiple protective mechanisms and provides new clues of parallel adaptive evolution in Antarctic psychrophilic green algae.

scholarly journals Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population

2019 ◽  
Vol 28 (3) ◽  
pp. 378-382 ◽  
Author(s):  
Saori Sakaue ◽  
Masato Akiyama ◽  
Makoto Hirata ◽  
Koichi Matsuda ◽  
Yoshinori Murakami ◽  
...  
Keyword(s):  
Positive Selection ◽  
Survival Data ◽  
Large Scale ◽  
Synergistic Effects ◽  
Additive Model ◽  
Asian Population ◽  
Beneficial Effects ◽  
Japanese Cohort ◽  
Functional Variants ◽  
Modern Population

Abstract The functional variants involved in alcohol metabolism, the A allele of rs1229984:A > G in ADH1B and the A allele of rs671:G > A in ALDH2, are specifically prevalent among East Asian population. They are shown to be under recent positive selection, but the reasons for the selection are unknown. To test whether these positively selected variants have beneficial effects on survival in modern population, we performed the survival analyses using the large-scale Japanese cohort (n = 135,974) with genotype and follow-up survival data. The rs671-A allele was significantly associated with the better survival in the additive model (HR for mortality = 0.960, P = 1.7 × 10−5), and the rs1229984-A had both additive and non-additive effects (HR = 0.962, P = 0.0016 and HR = 0.958, P = 0.0066, respectively), which was consistent with the positive selection. The favorable effects of these alleles on survival were independent of the habit of alcohol consumption itself. The heterogenous combinatory effect between rs1229984 and rs671 genotype was also observed (HRs for AA genotype at rs671 were 1.03, 0.80, and 0.90 for GG, GA, and AA genotype at rs1229984, respectively), supposedly reflecting the synergistic effects on survival.

scholarly journals Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection

2019 ◽  
Vol 36 (6) ◽  
pp. 1316-1332 ◽  
Author(s):  
Iakov I Davydov ◽  
Nicolas Salamin ◽  
Marc Robinson-Rechavi
Keyword(s):  
Comparative Analysis ◽  
Large Scale ◽  
Codon Models

Novel driver genes and genomic predictors of immune infiltrates in colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 557-557
Author(s):  
Marios Giannakis ◽  
Jasmine Xinmeng Mu ◽  
Sachet Shukla ◽  
Zhi Rong Qian ◽  
Ofir Cohen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Positive Selection ◽  
Exome Sequencing ◽  
Survival Data ◽  
Antigen Processing ◽  
Large Scale ◽  
Immune Cell ◽  
Health Study ◽  
Driver Genes ◽  
Immune Infiltration

557 Background: Despite progress that has been made in the molecular characterization of colorectal cancer (CRC), prior studies have had limited power to detect, as significantly mutated, less-frequently altered CRC genes. In addition, most large-scale sequencing studies have generally lacked clinicopathologic annotations to link genomic features with important CRC characteristics such as immune infiltration. Methods: We performed Whole-Exome Sequencing on 619 archival primary CRCs from two large prospective cohorts, the Nurses’ Health Study and the Health Professionals Follow-Up Study. We identified CRC driver genes using significance-calling algorithms and employed a novel computational pipeline to calculate tumor neoantigens (peptides resulting from somatic mutations and recognized by the immune system as foreign). The neoantigen load and altered genes/pathways were correlated to immunohistochemically determined immune infiltrates and survival data linked to these specimens. Results: We identified 90 significantly mutated genes in non-hypermutated CRC. These include previously underappreciated genes that participate in pathways such as WNT-signaling and RNA processing. Among all samples, the neoantigen load was associated with increased overall lymphocytic infiltration (P = 2.6e-11), tumor-infiltrating lymphocytes (TILs) (P = 2.0e-19), memory T-cells (P = 0.091) and CRC-specific survival (P = 0.025). Neoantigen load was also associated with higher TILs in microsatellite-stable tumors (P = 0.015). We found that HLA and Antigen Processing Machinery (APM) mutations have undergone positive selection in tumors with TILs. Conclusions: In the largest exome-sequencing study of CRC to date, we leveraged the increased number of samples and their associated clinicopathologic annotations to identify new driver genes and genomic predictors of immune infiltrates in this disease. Neoantigen load is prognostic in CRC and predictive of immune infiltration, even among microsatellite-stable tumors. We also find evidence of positive selection for HLA and APM mutations in immune-cell infiltrated tumors. These results have implications for patient selection in CRC immunotherapy trials.

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