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      Adaptive Transcriptome Profiling of Subterranean Zokor, Myospalax baileyi, to High- Altitude Stresses in Tibet

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          Abstract

          Animals living at high altitudes have evolved distinct phenotypic and genotypic adaptations against stressful environments. We studied the adaptive patterns of altitudinal stresses on transcriptome turnover in subterranean plateau zokors ( Myospalax baileyi) in the high-altitude Qinghai-Tibetan Plateau. Transcriptomes of zokors from three populations with distinct altitudes and ecologies ( Low: 2846 m, Middle: 3282 m, High: 3,714 m) were sequenced and compared. Phylogenetic and principal component analyses classified them into three divergent altitudinal population clusters. Genetic polymorphisms showed that the population at H, approaching the uppermost species boundary, harbors the highest genetic polymorphism. Moreover, 1056 highly up-regulated UniGenes were identified from M to H. Gene ontologies reveal genes like EPAS1 and COX1 were overexpressed under hypoxia conditions. EPAS1, EGLN1, and COX1 were convergent in high-altitude adaptation against stresses in other species. The fixation indices ( F ST and G ST )-based outlier analysis identified 191 and 211 genes, highly differentiated among L, M, and H. We observed adaptive transcriptome changes in Myospalax baileyi, across a few hundred meters, near the uppermost species boundary, regardless of their relatively stable underground burrows’ microclimate. The highly variant genes identified in Myospalax were involved in hypoxia tolerance, hypercapnia tolerance, ATP-pathway energetics, and temperature changes.

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          Estimation of average heterozygosity and genetic distance from a small number of individuals.

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          The magnitudes of the systematic biases involved in sample heterozygosity and sample genetic distances are evaluated, and formulae for obtaining unbiased estimates of average heterozygosity and genetic distance are developed. It is also shown that the number of individuals to be used for estimating average heterozygosity can be very small if a large number of loci are studied and the average heterozygosity is low. The number of individuals to be used for estimating genetic distance can also be very small if the genetic distance is large and the average heterozygosity of the two species compared is low.
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            Diversity and dynamics of the Drosophila transcriptome

            Animal transcriptomes are dynamic, each cell type, tissue and organ system expressing an ensemble of transcript isoforms that give rise to substantial diversity. We identified new genes, transcripts, and proteins using poly(A)+ RNA sequence from Drosophila melanogaster cultured cell lines, dissected organ systems, and environmental perturbations. We found a small set of mostly neural-specific genes has the potential to encode thousands of transcripts each through extensive alternative promoter usage and RNA splicing. The magnitudes of splicing changes are larger between tissues than between developmental stages, and most sex-specific splicing is gonad-specific. Gonads express hundreds of previously unknown coding and long noncoding RNAs (lncRNAs) some of which are antisense to protein-coding genes and produce short regulatory RNAs. Furthermore, previously identified pervasive intergenic transcription occurs primarily within newly identified introns. The fly transcriptome is substantially more complex than previously recognized arising from combinatorial usage of promoters, splice sites, and polyadenylation sites.
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              Human polymorphism at microRNAs and microRNA target sites.

              MicroRNAs (miRNAs) function as endogenous translational repressors of protein-coding genes in animals by binding to target sites in the 3' UTRs of mRNAs. Because a single nucleotide change in the sequence of a target site can affect miRNA regulation, naturally occurring SNPs in target sites are candidates for functional variation that may be of interest for biomedical applications and evolutionary studies. However, little is known to date about variation among humans at miRNAs and their target sites. In this study, we analyzed publicly available SNP data in context with miRNAs and their target sites throughout the human genome, and we found a relatively low level of variation in functional regions of miRNAs, but an appreciable level of variation at target sites. Approximately 400 SNPs were found at experimentally verified target sites or predicted target sites that are otherwise evolutionarily conserved across mammals. Moreover, approximately 250 SNPs potentially create novel target sites for miRNAs in humans. If some variants have functional effects, they might confer phenotypic differences among humans. Although the majority of these SNPs appear to be evolving under neutrality, interestingly, some of these SNPs are found at relatively high population frequencies even in experimentally verified targets, and a few variants are associated with atypically long-range haplotypes that may have been subject to recent positive selection.
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                Author and article information

                Contributors
                milana.morgenstern@biu.ac.il
                zhangtz@nwipb.cas.cn
                nevo@research.haifa.ac.il
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 March 2018
                16 March 2018
                2018
                : 8
                : 4671
                Affiliations
                [1 ]ISNI 0000000119573309, GRID grid.9227.e, Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, , Chinese Academy of Sciences, ; Xining, 810008 China
                [2 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, University of Chinese Academy of Sciences, No.19A Yuquan Road, ; Beijing, 100049 China
                [3 ]ISNI 0000000100241216, GRID grid.189509.c, Department of Molecular Genetics and Microbiology, Duke University Medical Center, ; Durham, NC 27708 USA
                [4 ]ISNI 0000 0001 2189 3846, GRID grid.207374.5, School of Life Sciences, Zhengzhou University, ; Zhengzhou, 450001 Henan China
                [5 ]ISNI 0000 0004 1937 0503, GRID grid.22098.31, The Azrieli Faculty of Medicine, , Bar-Ilan University, ; Safed, 13195 Israel
                [6 ]ISNI 0000 0001 0526 1937, GRID grid.410727.7, Institute of Apicultural Research, , Chinese Academy of Agricultural Sciences, ; Beijing, 100093 China
                [7 ]ISNI 0000 0004 1937 0562, GRID grid.18098.38, The Institute of Evolution, , University of Haifa, 199 Aba Khoushy Ave, ; Mount Carmel, Haifa 3498838 Israel
                [8 ]ISNI 0000 0004 1792 5587, GRID grid.454850.8, Key Laboratory of Experimental Marine Biology, , Institute of Oceanology, Chinese Academy of Sciences, ; Qingdao, 266071 Shandong China
                [9 ]Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, 810008 China
                Author information
                http://orcid.org/0000-0001-9556-2361
                Article
                22483
                10.1038/s41598-018-22483-7
                5856782
                29549310
                d805aa2d-dec1-47ad-b9ac-338460f2e460
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 May 2017
                : 30 January 2018
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