抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Recent advances in sequencing technology make it possible to comprehensively catalogue genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (1) initial read mapping; (2) local realignment around indels; (3) base quality score recalibration; (4) SNP discovery and genotyping to find all potential variants; and (5) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We discuss the application of these tools, instantiated in the Genome Analysis Toolkit (GATK), to deep whole-genome, whole-exome capture, and multi-sample low-pass (~4×) 1000 Genomes Project datasets.

/pdf/a-framework-for-variation-discovery-and-genotyping-using-1mhes6klgp.pdf

A framework for variation discovery and genotyping using next-generation DNA sequencing data

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Dissecting plant responses to the environment is key to understanding if and how plants adapt to anthropogenic climate change. Stomata, plants’ pores for gas exchange, are expected to decrease in density following increased CO2 concentrations, a trend already observed in multiple plant species. However, it is unclear if such responses are based on genetic changes and evolutionary adaptation. Here we make use of extensive knowledge of 43 genes in the stomatal development pathway and newly generated genome information of 191 A. thaliana historical herbarium specimens collected over the last 193 years to directly link genetic variation with climate change. While we find that the essential transcription factors SPCH, MUTE and FAMA, central to stomatal development, are under strong evolutionary constraints, several regulators of stomatal development show signs of local adaptation in contemporary samples from different geographic regions. We then develop a polygenic score based on known effects of gene knock-out on stomatal development that recovers a classic pattern of stomatal density decrease over the last centuries without requiring direct phenotype observation of historical samples. This approach combining historical genomics with functional experimental knowledge could allow further investigations of how different, even in historical samples unmeasurable, cellular plant phenotypes have already responded to climate change through adaptive evolution. One sentence summary Using a molecular-knowledge based genetic phenotype proxy, historical whole-genome A. thaliana timelines compared with contemporary data indicate a shift of stomatal density following climate-associated predictions.

/pdf/century-long-timelines-of-herbarium-genomes-predict-plant-2x818lsk.pdf

Century-long timelines of herbarium genomes predict plant stomatal response to climate change

DNA extracted from herbarium specimens is highly fragmented and decays at a faster rate than DNA from ancient bones. Therefore, it is crucial to utilize extraction protocols that retrieve short DNA molecules. Improvements in extraction and library preparation protocols for animal remains have allowed efficient retrieval of molecules shorter than 50 bp. We adapted those improvements to extraction protocols for herbarium specimens and evaluated their performance by shotgun sequencing, which allows an accurate estimation of the distribution of fragment lengths. Extraction with PTB buffer decreased median fragment length by 35% when compared to CTAB. Modifying the binding conditions of DNA to silica allowed for an additional decrease of 10%. We did not observe a further decrease in length when we used single-stranded instead of double-stranded library preparation methods. Our protocol enables the retrieval of ultrashort molecules from herbarium specimens and will help to unlock the genetic information stored in herbaria.

https://www.biorxiv.org/content/biorxiv/early/2016/09/20/076299.full.pdf

Hernán A. Burbano

Papers

Century-long timelines of herbarium genomes predict plant stomatal response to climate change

Extraction of ultrashort DNA molecules from herbarium specimens