A novel multi-alignment pipeline for high-throughput sequencing data

Huang, Shangyu; Holt, James; Kao, Chia Yu; McMillan, Leonard; Wang, Wei

doi:10.1093/database/bau057

Cited by 45 publications

(59 citation statements)

References 20 publications

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“…C57BL/6J (Huang et al 2014). This approach leverages the extensive annotation developed for the mouse genome while minimizing mapping bias that favors reads matching the C57BL/6J reference, which is predominantly derived from M. m. domesticus (Yang et al 2011).…”

Section: Molecular Evolution Of Spermatogenesis 1843mentioning

confidence: 99%

Contrasting Levels of Molecular Evolution on the Mouse X Chromosome

et al. 2016

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The mammalian X chromosome has unusual evolutionary dynamics compared to autosomes. Faster-X evolution of spermatogenic protein-coding genes is known to be most pronounced for genes expressed late in spermatogenesis, but it is unclear if these patterns extend to other forms of molecular divergence. We tested for faster-X evolution in mice spanning three different forms of molecular evolution-divergence in protein sequence, gene expression, and DNA methylation-across different developmental stages of spermatogenesis. We used FACS to isolate individual cell populations and then generated cell-specific transcriptome profiles across different stages of spermatogenesis in two subspecies of house mice (Mus musculus), thereby overcoming a fundamental limitation of previous studies on whole tissues. We found faster-X protein evolution at all stages of spermatogenesis and faster-late protein evolution for both X-linked and autosomal genes. In contrast, there was less expression divergence late in spermatogenesis (slower late) on the X chromosome and for autosomal genes expressed primarily in testis (testis-biased). We argue that slower-late expression divergence reflects strong regulatory constraints imposed during this critical stage of sperm development and that these constraints are particularly acute on the tightly regulated sex chromosomes. We also found slower-X DNA methylation divergence based on genome-wide bisulfite sequencing of sperm from two species of mice (M. musculus and M. spretus), although it is unclear whether slower-X DNA methylation reflects development constraints in sperm or other X-linked phenomena. Our study clarifies key differences in patterns of regulatory and protein evolution across spermatogenesis that are likely to have important consequences for mammalian sex chromosome evolution, male fertility, and speciation.KEYWORDS faster X evolution; gene expression; DNA methylation; fluorescence-activated cell sorting; postmeiotic sex chromosome repression (PSCR) T HE X chromosome plays a disproportionately large role in adaptation and speciation (Bachtrog et al. 2011;Ellegren 2011;Charlesworth 2013), but the underlying molecular and evolutionary drivers of these patterns remain unclear. On one hand, the X chromosome often shows strong signatures of evolutionary constraint. For example, the evolution of dosage compensation via epigenetic X-chromosome inactivation (XCI) in females (Lyon 1961(Lyon , 1962 imposes regulatory constraints that select for strong conservation of X-linked gene content in placental mammals (Ohno 1967;Kohn et al. 2004). On the other hand, these inherent constraints are punctuated by strong specialization in X-linked gene content (Emerson et al. 2004;Mueller et al. 2008Mueller et al. , 2013Potrzebowski et al. 2008;Zhang et al. 2010;Sin et al. 2012) and numerous examples of rapid X-linked evolution Singh 2003, 2006;Baines and Harr 2007;Kousathanas et al. 2014;Nam et al. 2015).The X chromosome is predicted to evolve faster than the autosomes if beneficial mutations...

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Section: Molecular Evolution Of Spermatogenesis 1843mentioning

confidence: 99%

Contrasting Levels of Molecular Evolution on the Mouse X Chromosome

et al. 2016

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“…We constructed strain-specific transcriptomes for seven of the eight founder strains (except C57BL/6J) using ModTools (Huang et al 2014). We incorporated strain-specific SNPs and short (,50 bp) indels from the Sanger Mouse Genomes Project Yalcin et al 2011) (REL-1303 into the Genome Reference Consortium Mouse Genome,…”

Section: Rna Editing Site Prediction In Founder Strainsmentioning

confidence: 99%

“…We converted transcriptome alignments to genome alignments using rsem-tbam2gbam (Li and Dewey 2011) and adjusted the strain-specific coordinates to GRCm38 coordinates using Lapels (Huang et al 2014).…”

Section: Rna Editing Site Prediction In Founder Strainsmentioning

confidence: 99%

“…All 16 replicates from each strain were aligned to their respective strain-specific transcriptome using Bowtie with parameters -a -best -strata -v 3. We converted transcriptome alignments to genome alignments using rsem-tbam2gbam (Li and Dewey 2011) and adjusted the strain-specific coordinates to GRCm38 coordinates using Lapels (Huang et al 2014).We piled up the reads within each transcript (Ensembl archive 68) for each of the 16 replicates in a single DO founder strain. For each founder strain, we retained sites with the following properties: Our reconstructions of founder strain and individual DO transcriptomes are based on the current mouse reference genome (GRCm38) and include annotated pseudogenes.…”

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Genetic Architectures of Quantitative Variation in RNA Editing Pathways

Gatti

Srivastava

et al. 2015

Genetics

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RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing.KEYWORDS genetics; RNA editing; Diversity Outbred; Apobec1; secondary structure; Multiparent Advanced Generation Inter-Cross (MAGIC); multiparental populations; MPP R NA EDITING in mammals occurs through deamination of adenosine, which is converted to inosine (A-to-I editing), or deamination of cytosine, which is converted to uracil (C-to-U editing) (Davidson and Shelness 2000;Bass 2002). Other types of editing have been reported, but these findings remain controversial (Bass et al. 2012;Gu et al. 2012). The two canonical editing types, A-to-I and C-to-U editing, are mediated by distinct pathways. A-to-I editing is catalyzed on double-stranded (ds) RNA by proteins in the adenosine deaminase, RNA-specific (ADAR) family (ADAR1 and ADAR2) and is most common in neuronal tissues. However, the Adar gene family is ubiquitously expressed, and editing has been reported in many other tissues (Gu et al. 2012).Homozygous deletion of Adar genes is embryonic lethal in mice, and defects in A-to-I editing have been associated with neurodegenerative disorders and cancers (Gurevich et al. 2002;Paz et al. 2007). The C-to-U editing pathway is catalyzed by apolipoprotein B messenger RNA (mRNA) editing enzyme catalytic polypeptide 1 (Apobec1), which is expressed primarily in small intestine and liver, where it targets the transcript of apolipoprotein B (Apob), converting a CAA (glutamine) codon within the coding sequence to a stop codon (UAA). This editing event results in two APOB protein isoforms, APOB48 from the edited transcript and APOB100 from the unedited transcript. Editing of Apob is evolutionarily conserved and occurs in mice, humans, and other mammals. The edited isoform APOB48 functions in the synthesis, assembly, and secretion of chylomicrons in the small intestine; the unedited isoform APOB100 is expressed in the liver and gives ris...

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Informatics resources for the Collaborative Cross and related mouse populations

Morgan

Welsh

2015

Mamm Genome

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A novel multi-alignment pipeline for high-throughput sequencing data

Cited by 45 publications

References 20 publications

Contrasting Levels of Molecular Evolution on the Mouse X Chromosome

Contrasting Levels of Molecular Evolution on the Mouse X Chromosome

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

Informatics resources for the Collaborative Cross and related mouse populations

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