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

Directed evolution circumvents our profound ignorance of how a protein's sequence encodes its function by using iterative rounds of random mutation and artificial selection to discover new and useful proteins. Proteins can be tuned to adapt to new functions or environments by simple adaptive walks involving small numbers of mutations. Directed evolution studies have shown how rapidly some proteins can evolve under strong selection pressures and, because the entire 'fossil record' of evolutionary intermediates is available for detailed study, they have provided new insight into the relationship between sequence and function. Directed evolution has also shown how mutations that are functionally neutral can set the stage for further adaptation.

/pdf/exploring-protein-fitness-landscapes-by-directed-evolution-4wy4f2twej.pdf

Exploring protein fitness landscapes by directed evolution

Over the past thirty years, a new systemic conception of life has emerged at the forefront of science. New emphasis has been given to complexity, networks, and patterns of organisation, leading to a novel kind of 'systemic' thinking. This volume integrates the ideas, models, and theories underlying the systems view of life into a single coherent framework. Taking a broad sweep through history and across scientific disciplines, the authors examine the appearance of key concepts such as autopoiesis, dissipative structures, social networks, and a systemic understanding of evolution. The implications of the systems view of life for health care, management, and our global ecological and economic crises are also discussed. Written primarily for undergraduates, it is also essential reading for graduate students and researchers interested in understanding the new systemic conception of life and its implications for a broad range of professions - from economics and politics to medicine, psychology and law.

The Systems View of Life: A Unifying Vision

The design of artificial catalysts able to compete with the catalytic proficiency of enzymes is an intense subject of research. Non-covalent interactions are thought to be involved in several properties of enzymatic catalysis, notably (i) the confinement of the substrates and the active site within a catalytic pocket, (ii) the creation of a hydrophobic pocket in water, (iii) self-replication properties and (iv) allosteric properties. The origins of the enhanced rates and high catalytic selectivities associated with these properties are still a matter of debate. Stabilisation of the transition state and favourable conformations of the active site and the product(s) are probably part of the answer. We present here artificial catalysts and biomacromolecule hybrid catalysts which constitute good models towards the development of truly competitive artificial enzymes.

/pdf/supramolecular-catalysis-part-2-artificial-enzyme-mimics-2h1esy0td8.pdf

Supramolecular catalysis. Part 2: artificial enzyme mimics

Kepa Ruiz-Mirazo,†,∥ Carlos Briones,‡,∥ and Andreś de la Escosura* †Biophysics Unit (CSIC-UPV/EHU), Leioa, and Department of Logic and Philosophy of Science, University of the Basque Country, Avenida de Tolosa 70, 20080 Donostia−San Sebastiań, Spain ‡Department of Molecular Evolution, Centro de Astrobiología (CSIC−INTA, associated to the NASA Astrobiology Institute), Carretera de Ajalvir, Km 4, 28850 Torrejoń de Ardoz, Madrid, Spain Organic Chemistry Department, Universidad Autońoma de Madrid, Cantoblanco, 28049 Madrid, Spain

Prebiotic systems chemistry: new perspectives for the origins of life.

An RNA enzyme that catalyzes the RNA-templated joining of RNA was converted to a format whereby two enzymes catalyze each other's synthesis from a total of four oligonucleotide substrates These cross-replicating RNA enzymes undergo self-sustained exponential amplification in the absence of proteins or other biological materials Amplification occurs with a doubling time of about 1 hour and can be continued indefinitely Populations of various cross-replicating enzymes were constructed and allowed to compete for a common pool of substrates, during which recombinant replicators arose and grew to dominate the population These replicating RNA enzymes can serve as an experimental model of a genetic system Many such model systems could be constructed, allowing different selective outcomes to be related to the underlying properties of the genetic system

/pdf/self-sustained-replication-of-an-rna-enzyme-4wyq9s1m7w.pdf

Self-Sustained Replication of an RNA Enzyme

Here, we report a form of oligonucleotide-directed mutagenesis for precision genome editing in plants that uses single-stranded oligonucleotides (ssODNs) to precisely and efficiently generate genome edits at DNA strand lesions made by DNA double strand break reagents. Employing a transgene model in Arabidopsis (Arabidopsis thaliana), we obtained a high frequency of precise targeted genome edits when ssODNs were introduced into protoplasts that were pretreated with the glycopeptide antibiotic phleomycin, a nonspecific DNA double strand breaker. Simultaneous delivery of ssODN and a site-specific DNA double strand breaker, either transcription activator-like effector nucleases (TALENs) or clustered, regularly interspaced, short palindromic repeats (CRISPR/Cas9), resulted in a much greater targeted genome-editing frequency compared with treatment with DNA double strand-breaking reagents alone. Using this site-specific approach, we applied the combination of ssODN and CRISPR/Cas9 to develop an herbicide tolerance trait in flax (Linum usitatissimum) by precisely editing the 5′-ENOLPYRUVYLSHIKIMATE-3-PHOSPHATE SYNTHASE (EPSPS) genes. EPSPS edits occurred at sufficient frequency that we could regenerate whole plants from edited protoplasts without employing selection. These plants were subsequently determined to be tolerant to the herbicide glyphosate in greenhouse spray tests. Progeny (C1) of these plants showed the expected Mendelian segregation of EPSPS edits. Our findings show the enormous potential of using a genome-editing platform for precise, reliable trait development in crop plants.

/pdf/oligonucleotide-mediated-genome-editing-provides-precision-tmr0c6qjza.pdf

Tracey A. Lincoln

Papers

Self-Sustained Replication of an RNA Enzyme

Oligonucleotide-mediated genome editing provides precision and function to engineered nucleases and antibiotics in plants