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      Comparative genomics reveals putative evidence for high-elevation adaptation in the American pika ( Ochotona princeps)


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          High-elevation environments have lower atmospheric oxygen content, reduced temperatures, and higher levels of UV radiation than found at lower elevations. As such, species living at high elevations must overcome these challenges to survive, grow, and reproduce. American pikas ( Ochotona princeps) are alpine lagomorphs that are habitat specialists typically found at elevations >2,000 m. Previous research has shown putative evidence for high-elevation adaptation; however, investigations to date have been limited to a fraction of the genome. Here, we took a comparative genomics approach to identify putative regions under selection using a chromosomal reference genome assembly for the American pika relative to 8 other mammalian species targeted based on phylogenetic relatedness and (dis)similarity in ecology. We first identified orthologous gene groups across species and then extracted groups containing only American pika genes as well as unclustered pika genes to inform functional enrichment analyses; among these, we found 141 enriched terms with many related to hypoxia, metabolism, mitochondrial function/development, and DNA repair. We identified 15 significantly expanded gene families within the American pika across all orthologous gene groups that displayed functionally enriched terms associated with hypoxia adaptation. We further detected 196 positively selected genes, 41 of which have been associated with putative adaptation to hypoxia, cold tolerance, and response to UV following a literature review. In particular, OXNAD1, NRDC, and those genes critical in DNA repair represent important targets for future research to examine their functional implications in the American pika, especially as they may relate to adaptation to rapidly changing environments.

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          MUSCLE: multiple sequence alignment with high accuracy and high throughput.

          We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the log-expectation score, and refinement using tree-dependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.
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            MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space

            Since its introduction in 2001, MrBayes has grown in popularity as a software package for Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) methods. With this note, we announce the release of version 3.2, a major upgrade to the latest official release presented in 2003. The new version provides convergence diagnostics and allows multiple analyses to be run in parallel with convergence progress monitored on the fly. The introduction of new proposals and automatic optimization of tuning parameters has improved convergence for many problems. The new version also sports significantly faster likelihood calculations through streaming single-instruction-multiple-data extensions (SSE) and support of the BEAGLE library, allowing likelihood calculations to be delegated to graphics processing units (GPUs) on compatible hardware. Speedup factors range from around 2 with SSE code to more than 50 with BEAGLE for codon problems. Checkpointing across all models allows long runs to be completed even when an analysis is prematurely terminated. New models include relaxed clocks, dating, model averaging across time-reversible substitution models, and support for hard, negative, and partial (backbone) tree constraints. Inference of species trees from gene trees is supported by full incorporation of the Bayesian estimation of species trees (BEST) algorithms. Marginal model likelihoods for Bayes factor tests can be estimated accurately across the entire model space using the stepping stone method. The new version provides more output options than previously, including samples of ancestral states, site rates, site d N /d S rations, branch rates, and node dates. A wide range of statistics on tree parameters can also be output for visualization in FigTree and compatible software.
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              BLAST+: architecture and applications

              Background Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. Results We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. Conclusion The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications.

                Author and article information

                Role: Editor
                G3 (Bethesda)
                G3: Genes|Genomes|Genetics
                Oxford University Press
                November 2022
                10 September 2022
                10 September 2022
                : 12
                : 11
                : jkac241
                Department of Biology, University of British Columbia, Okanagan Campus , Kelowna, V1V 1V7 BC, Canada
                Department of Biology, University of British Columbia, Okanagan Campus , Kelowna, V1V 1V7 BC, Canada
                Author notes
                Corresponding author: Department of Biology, University of British Columbia, Okanagan Campus, 3247 University Way, Kelowna, V1V 1V7 BC, Canada. Email: michael.russello@ 123456ubc.ca
                Author information
                © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 13 June 2022
                : 07 September 2022
                : 26 September 2022
                Page count
                Pages: 12
                Funded by: Natural Sciences and Engineering Research Council of Canada Discovery;
                Award ID: RGPIN-2019-04621

                comparative genomics,local adaptation,cold tolerance,uv radiation,hypoxia,lagomorpha
                comparative genomics, local adaptation, cold tolerance, uv radiation, hypoxia, lagomorpha


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