Transposable elements shape the human proteome landscape via formation of cis‐acting upstream open reading frames

Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis‐acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed “transposon‐derived upstream ATGs” or TuATGs. Luciferase reporter assays suggested that many TuATGs modulate translation from anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs were generated by nucleotide substitutions in non‐ATG trinucleotides of integrated transposons. Among these non‐ATG trinucleotides, GTG and ACG were converted into TuATGs more frequently, indicating a CpG methylation‐mediated process of TuATG formation. Interestingly, it is likely that this process accelerated human‐specific upstream ATG formation within transposon sequences in 5′ untranslated regions after divergence between human and nonhuman primates. Methylation‐mediated TuATG formation seems to be ongoing in the modern human population and could alter the expression of disease‐related proteins. This study shows that transposons have potentially been shaping the human proteome landscape via cis‐acting uORF creation.     

本草名词艾叶演变探析

艾作为一味中药,其名称最早出现在《诗经》中,其后又在本草古籍中称为艾蒿、灸草、蕲艾、黄草、医草、家艾、甜艾、草蓬、艾蓬、狼尾蒿子、香艾、野莲头、阿及艾、艾叶等等,其功用和主治也发生了变化,文章试就艾的发展演变进行探讨。     

舟山市3例发热伴血小板减少综合征的病原学与遗传特征

目的 对舟山市3例疑似发热伴血小板减少综合征(SFTS)病例进行病原学鉴定、确诊,并分析其遗传特征.方法 选用巢式RT-PCR测定新布尼亚病毒核酸及L、M、S3个特异性基因,并对基因扩增产物进行测序,测序结果与GenBank上公布的序列进行比对确认.用DNAStar软件构建进化树与序列距离表.用间接免疫荧光法测定患者恢复期和急性期血清新布尼亚病毒IgG抗体滴度.结果 3例SFTS患者急性期血清中均能检测到新布尼亚病毒的3个特异性基因片段,其中S基因核苷酸序列与舟山市同类基因核苷酸序列的同源性在94.4％～ 100.0％,患者恢复期血清病毒抗体滴度较急性期增高4倍以上.结论 经过病原学鉴定,3例临床疑似患者确诊为发热伴血小板减少综合征的新近感染病例.舟山市新布尼亚病毒的遗传特征比较稳定.     

Comparative anatomy of neonates of the three major mammalian groups (monotremes,marsupials, placentals) and implications for the ancestral mammalian neonate morphotype

The existing different modes of reproduction in monotremes, marsupials and placentals are the main source for our current understanding of the origin and evolution of the mammalian reproduction. The reproductive strategies and, in particular, the maturity states of the neonates differ remarkably between the three groups. Monotremes, for example, are the only extant mammals that lay eggs and incubate them for the last third of their embryonic development. In contrast, marsupials and placentals are viviparous and rely on intra‐uterine development of the neonates via choriovitelline (mainly marsupials) and chorioallantoic (mainly placentals) placentae. The maturity of a newborn is closely linked to the parental care strategy once the neonate is born. The varying developmental degrees of neonates are the main focus of this study. Monotremes and marsupials produce highly altricial and nearly embryonic offspring. Placental mammals always give birth to more developed newborns with the widest range from altricial to precocial. The ability of a newborn to survive and grow in the environment it was born in depends highly on the degree of maturation of vital organs at the time of birth. Here, the anatomy of four neonates of the three major extant mammalian groups is compared. The basis for this study is histological and ultrastructural serial sections of a hatchling of Ornithorhynchus anatinus (Monotremata), and neonates of Monodelphis domestica (Marsupialia), Mesocricetus auratus (altricial Placentalia) and Macroscelides proboscideus (precocial Placentalia). Special attention was given to the developmental stages of the organs skin, lung, liver and kidney, which are considered crucial for the maintenance of vital functions. The state of the organs of newborn monotremes and marsupials are found to be able to support a minimum of vital functions outside the uterus. They are sufficient to survive, but without capacities for additional energetic challenges. The organs of the altricial placental neonate are further developed, able to support the maintenance of vital functions and short‐term metabolic increase. The precocial placental newborn shows the most advanced state of organ development, to allow the maintenance of vital functions, stable thermoregulation and high energetic performance. The ancestral condition of a mammalian neonate is interpreted to be similar to the state of organ development found in the newborns of marsupials and monotremes. In comparison, the newborns of altricial and precocial placentals are derived from the ancestral state to a more mature developmental degree associated with advanced organ systems.     

Evidence of a conserved functional role for DNA methylation in termites

Many organisms are capable of developing distinct phenotypes from the same genotype. This developmental plasticity is particularly prevalent in insects, which can produce alternate adaptive forms in response to distinct environmental cues. The ability to develop divergent phenotypes from the same genotype often relies on epigenetic information, which affects gene function and is transmitted through cell divisions. One of the most important epigenetic marks, DNA methylation, has been lost in several insect lineages, yet its taxonomic distribution and functional conservation remain uninvestigated in many taxa. In the present study, we demonstrate that the signature of high levels of DNA methylation exists in the expressed genes of two termites, Reticulitermes flavipes and Coptotermes formosanus. Further, we show that DNA methylation is preferentially targeted to genes with ubiquitous expression among morphs. Functional associations of DNA methylation are also similar to those observed in other invertebrate taxa with functional DNA methylation systems. Finally, we demonstrate an association between DNA methylation and the long‐term evolutionary conservation of genes. Overall, our findings strongly suggest DNA methylation is present at particularly high levels in termites and may play similar roles to those found in other insects.     

Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents

Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Primary H. pylori susceptibility patterns, however, are becoming less predictable. Currently, high (≥20%) clarithromycin resistance rates have been observed in the USA and in developed countries in Europe and Asia, while the highest (≥80%) metronidazole-resistance rates have been reported in Africa, Asia and South America. Primary quinolone-resistance rates of 10% or more have already been reported in developed countries in Europe and Asia. Primary amoxicillin resistance has been low (0 to <2%) in Europe but higher (6–59%) in Africa, Asia and South America. Similarly, tetracycline resistance has been absent or low (<5%) in most countries and higher (9–27%) in Asia and South America. The increasing clarithromycin and quinolone resistance, and multidrug resistance detected in 0 to less than 5% in Europe and more often (14.2%) in Brazil are worrying. Growing resistance often parallels national antibiotic consumption and may vary within patient groups according to the geographic region, patient’s age and sex, type of disease, birthplace, other infections and other factors. The geographic map and evolution of primary H. pylori resistance are clinically important, should be considered when choosing eradication regimens, and should be monitored constantly at national and global levels in an attempt to reach the recently recommended goal of eradication of more than 95%.     

Learning from nature – Novel synthetic biology approaches for biomaterial design

Many biomaterials constructed today are complex chemical structures that incorporate biologically active components derived from nature, but the field can still be said to be in its infancy. The need for materials that bring sophisticated properties of structure, dynamics and function to medical and non-medical applications will only grow. Increasing appreciation of the functionality of biological systems has caused biomaterials researchers to consider nature for design inspiration, and many examples exist of the use of biomolecular motifs. Yet evolution, nature’s only engine for the creation of new designs, has been largely ignored by the biomaterials community. Molecular evolution is an emerging tool that enables one to apply nature’s engineering principles to non-natural situations using variation and selection. The purpose of this review is to highlight the most recent advances in the use of molecular evolution in synthetic biology applications for biomaterial engineering, and to discuss some of the areas in which this approach may be successfully applied in the future.     

The rediscovery of smallpox

Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts—variolation, quarantine, and the isolation of infected subjects—until Jenner’s discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease.