Effect of the DnaK chaperone on the conformational quality of JCV VP1 virus‐like particles produced in Escherichia coli

Protein nanoparticles such as virus‐like particles (VLPs) can be obtained by recombinant protein production of viral capsid proteins and spontaneous self‐assembling in cell factories. Contrarily to infective viral particles, VLPs lack infective viral genome while retaining important viral properties like cellular tropism and intracellular delivery of internalized molecules. These properties make VLPs promising and fully biocompatible nanovehicles for drug delivery. VLPs of human JC virus (hJCV) VP1 capsid protein produced in Escherichia coli elicit variable hemagglutination properties when incubated at different NaCl concentrations and pH conditions, being optimal at 200 mM NaCl and at pH range between 5.8 and 7.5. In addition, the presence or absence of chaperone DnaK in E. coli cells influence the solubility of recombinant VP1 and the conformational quality of this protein in the VLPs. The hemagglutination ability of hJCV VP1 VLPs contained in E. coli cell extracts can be modulated by buffer composition in the hemagglutination assay. It has been also determined that the production of recombinant hJCV VP1 in E. coli is favored by the absence of chaperone DnaK as observed by Western Blot analysis in different E. coli genetic backgrounds, indicating a proteolysis targeting role for DnaK. However, solubility is highly compromised in a DnaK^? E. coli strain suggesting an important role of this chaperone in reduction of protein aggregates. Finally, hemagglutination efficiency of recombinant VP1 is directly related to the presence of DnaK in the producing cells. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:744–748, 2014     

Migration distance rather than migration rate explains genetic diversity in human patrilocal groups

In patrilocal groups, females preferentially move to join their mate’s paternal relatives. The gender‐biased gene flow generated by this cultural practice is expected to affect genetic diversity across human populations. Greater female than male migration is predicted to result in a larger decrease in between‐group differentiation for mitochondrial DNA (mtDNA) than for the non‐recombining part of the Y chromosome (NRY). We address the question of how patrilocality affects the distribution of genetic variation in human populations controlling for confounding factors such as ethno‐linguistic heterogeneity and geographic distance which possibly explain the contradictory results observed in previous studies. By combining genetic and bio‐demographic data from Lesotho and Spain, we show that preferential female migration over short distances appears to minimize the impact of a generally higher female migration rate in patrilocal communities, suggesting patrilocality might influence genetic variation only at short ranges.     

戊型肝炎病毒遗传多样性和进化机制的研究进展

戊型肝炎病毒(hepatitis E virus, HEV)是一种引发全球急性病毒性肝炎的人兽共患病病原。HEV具有丰富的遗传多样性,不同基因型或基因亚型的流行与地理位置、宿主物种以及防控策略等密切相关。欧洲和美洲HEV流行株为HEV-3,包括3a-i亚型,而亚洲流行株含HEV-3和HEV-4;我国的流行毒株已从HEV-1进化到HEV-4。近年来,研究发现HEV进化的影响机制,包括同义密码子使用模式、氨基酸突变和基因重组等,其中氨基酸突变是病毒持续流行的主要驱动力。因此,本文就HEV的分类、全球流行特征、进化机制等进行综述,以期为戊型肝炎的有效防控以及疫苗开发提供参考。     

Peak and Persistent Excess of Genetic Diversity Following an Abrupt Migration Increase

Genetic diversity is essential for population survival and adaptation to changing environments. Demographic processes (e.g., bottleneck and expansion) and spatial structure (e.g., migration, number, and size of populations) are known to shape the patterns of the genetic diversity of populations. However, the impact of temporal changes in migration on genetic diversity has seldom been considered, although such events might be the norm. Indeed, during the millions of years of a species’ lifetime, repeated isolation and reconnection of populations occur. Geological and climatic events alternately isolate and reconnect habitats. We analytically document the dynamics of genetic diversity after an abrupt change in migration given the mutation rate and the number and sizes of the populations. We demonstrate that during transient dynamics, genetic diversity can reach unexpectedly high values that can be maintained over thousands of generations. We discuss the consequences of such processes for the evolution of species based on standing genetic variation and how they can affect the reconstruction of a population’s demographic and evolutionary history from genetic data. Our results also provide guidelines for the use of genetic data for the conservation of natural populations.     

熊猫等动物犬瘟热病毒附着蛋白基因的遗传多样性

为了研究犬瘟热病毒（ｃａｎｉｎｅ ｄｉｓｔｅｍｐｅｒ ｖｉｒｕｓ,ＣＤＶ）大熊猫株、小熊猫株和长春犬株附着蛋白（Ｈ）基因的遗传这异,对Ｈ基因进行了序列测定。上述３个ＣＤＶ毒株的Ｈ基因全长均为１９４６ｂｐ,开放阅读框架（ＯＲＦ）始于２１－２３位的ＡＴＧ,终止于１８４２－１８４４位的ＴＧＡ,编码６０７个氨基酸。与ＧｅｎＢａｎｋ中１５个ＣＤＶ株推导的Ｈ蛋白氨基酸序列比较发现,１６个野毒株潜在的Ｈ－联糖基     

Ancient human mtDNA genotypes from England reveal lost variation over the last millennium

We analysed the historical genetic diversity of human populations in Europe at the mtDNA control region for 48 ancient Britons who lived between ca AD 300 and 1000, and compared these with 6320 modern mtDNA genotypes from England and across Europe and the Middle East. We found that the historical sample shows greater genetic diversity than for modern England and other modern populations, indicating the loss of diversity over the last millennium. The pattern of haplotypic diversity was clearly European in the ancient sample, representing each of the modern haplogroups. There was also increased representation of one of the ancient haplotypes in modern populations. We consider these results in the context of possible selection or stochastic processes.     

被动迁移在抗性进化中的作用

为了明确迁移和基因交流在杀虫剂抗性基因进化中的作用,我们从四个不同的地区采集有机磷抗性的库蚊野生种群,利用淀粉电泳鉴定了各种群中存在的已知过量产生酯酶的分布频率,并通过5个假定的中性位点的电泳多态性分析了种群间的遗传多样性。结果表明种群间的基因交流是存在的,遗传分化与地理位置存在一定关系,而抗性等位基因A2一B2的分布却与种群间的遗传分化不一致。对这种差异的解释是：被动迁移(铁路运输等)加速了抗性基因的交流,而当抗性基因以自然迁飞的方式向周围地区扩散时,却是一个相对缓慢的过程。     

African Origin of Polyomavirus JC and Implications for Prehistoric Human Migrations

Abstract The presence of distinctive types of JC virus (JCV) in the main ethnic groups suggests a close coevolution with the human host. However, phylogenetic trees of JCV show a basal clade of European lineages (Types 1/4), whereas trees of human genes are coherent in placing the first split between African and non-African populations. This discrepancy places into question the effectiveness of JCV as a marker of human population history. The present study investigates the evolution of JCV using a large set of fully sequenced strains. Their relationships are first elucidated by principal coordinates analysis. It is suggested that Type 6 from West Africa could represent the ancestral type, while the peculiar phylogeny of Types 1/4 could reflect their direct origin from the ancestral lineage. Further credit to the African origin of JCV is provided by a neighbor-joining analysis based on slow-evolving sites. Sequence analysis of fast-evolving sites reveals that the deep emergence of Types 1/4 in the tree does not reflect a real evolutionary divergence; rather it is the implicit result of a remarkably different G + C content. The hypothesis that Types 1/4 originated directly from Type 6 is confirmed by examining the pattern of variation at a few specific fast-evolving sites. On the basis of this approach, a twofold exit of JCV from Africa is hypothesized: one in the direction of the Eurasian continent and another limited to Europe. These findings suggest that two distinct migrations of individuals played a key role in the peopling of Europe during prehistoric times.