Where did the BLOSUM62 alignment score matrix come from?

Many sequence alignment programs use the BLOSUM62 score matrix to score pairs of aligned residues. Where did BLOSUM62 come from?     

How to assess the pathogenicity of mutations in Charcot-Marie-Tooth disease and other diseases?

Knowledge whether a certain DNA variant is a pathogenic mutation or a harmless polymorphism is a critical issue in medical genetics, in which results of a molecular analysis may serve as a basis for diagnosis and genetic counseling. Due to its genetic heterogeneity expressed at the levels of loci, genes and mutations, Charcot-Marie-Tooth (CMT) disease can serve as a model group of clinically homogenous diseases for studying the pathogenicity of mutations. Close to a 17p11.2-p12 duplication occurring in 70% of patients with the demyelinating form of CMT disease, numerous mutations have been identified in poorly characterized genes coding for proteins of an unknown function. Functional analyses, segregation analyses of large pedigrees, and inclusion of large control groups are required to assess the potential pathogenicity of CMT mutations. Hence, the pathogenicity of numerous CMT mutations remains unclear. Some variants detected in the CMT genes and originally described as pathogenic mutations have been shown to have a polymorphic character. In contrast, polymorphisms initially considered harmless were later reclassified as pathogenic mutations. However, the process of assessing the pathogenicity of mutations, as presented in this study for CMT disorders, is a more general issue concerning all disorders with a genetic background. Since the number of DNA variants is still growing, in the near future geneticists will increasingly have to cope with the problem of pathogenicity of identified genetic variants.     

Why did the frequency of palatine torus increase in the ancient Anatolian populations?

The frequency of the palatine torus varies in various populations from different regions of the world. In this study, the change of frequency of palatine torus is examined using 387 skulls from 12 different ancient Anatolian populations in various periods ranging from the Early Bronze Age to the first quarter of the 20th century.While the frequency of palatine torus is 45% in the Early Bronze Age, this ratio steadily increases to 87% in the Ottoman Period and finally declines to 40% during the recent period. It was determined that the increase in the frequency of the palatine torus is statistically significant across different periods from the Early Bronze Age until the 20th century. Constituting a passageway between Asia and Europe and being located on the crossroads of the most important trade route of the Medieval Period, the Silk Road, Anatolia is known to have been subjected to recurring invasions and migrations since the 11th century A.D. Therefore, it is possible to say that, with the introduction of the Mongoloid influence in Anatolia, genetic flow has had a significant role in the observed increase in the frequency of this trait.     

Where did they come from? Genetic diversity and forensic investigation of the threatened palm species Butia eriospatha

Few studies have assessed the genetic diversity that exists in individuals that were illegally-traded. In this paper, we evaluate the genetic consequences of illegal trade of the palm species Butia eriospatha. Although it is protected by Brazilian environmental law, information about the genetic consequences of illegal trading which can be used to support conservation planning is still needed. The two main questions approached were: (a) do illegally-traded individuals have higher levels of genetic diversity than those found in wild populations; and (b) where did the illegally-traded individuals come from? To answer these questions, we used nine microsatellite loci to quantify the genetic diversity in eight wild populations (n = 390) and one group of individuals (n = 50) planted in an urban area of Southern Brazil. For the forensic investigation, an assignment exclusion-test was performed. Remarkably, the illegally-traded B. eriospatha individuals had more genetic variation than all of the studied wild B. eriospatha populations, suggesting that there is no single target population used by poachers. Accordingly, the multilocus assignment test indicated that the urban B. eriospatha individuals came from a variety of different populations, with 46 % coming from populations not surveyed in this study. In light of these results, we discuss the very real problem of illegal trading of B. eriospatha that must be quickly addressed. Our results provide information that can be used to help support B. eriospatha conservation.     

Asymmetric segregation: the shape of things to come?

Yeast mother cells pay a sacrifice during budding: they keep the extrachromosomal rDNA circles (ERCs) so that their buds have a full lifespan ahead. Two new studies indicate that retention of ERCs in mother cells occurs not by tethering to the nuclear periphery but rather by the simple rules of diffusion in a time-limited and complex landscape.     

Has the transition to agriculture reshaped the demographic structure of prehistoric populations? New evidence from the Levant

This paper presents the demographic changes that followed the transition from a hunting-gathering way of life (Natufian) to an agricultural, food-producing economy (Neolithic) in the southern Levant. The study is based on 217 Natufian (10,500-8,300 BC) skeletons and 262 Neolithic (8,300-5,500 BC) skeletons. Age and sex identification were carried out, and life tables were constructed. A five-parameter competing hazard model developed by Siler ([1979] Ecology 60:750-757) was used to smooth life-table data. No indication of increased mortality with the advent of agriculture was noted. On the contrary, both life expectancy at birth (24.6 vs. 25.5 years) and adults' mean age at death (31.2 vs. 32.1 years) increased slightly from the Natufian to the Neolithic period (assuming stationary populations). Yet the transition to agriculture affected males and females differently: mean age at death in the Natufian was higher for adult females compared to adult males, while in the Neolithic, it was the reverse. One interpretation given to the distribution of female ages at death is that with the onset of the Neolithic period, maternal mortality increased as a result of a concomitant increase in fertility. If the adoption of agriculture in the Levant increased the rate of population growth at the beginning of the Neolithic, expectation of life may have increased dramatically.     

How to prove the existence of metabolons?

Sequential enzymes in biosynthetic pathways are organized in metabolons. It is challenging to provide experimental evidence for the existence of metabolons as biosynthetic pathways are composed of highly dynamic protein–protein interactions. Many different methods are being applied, each with strengths and weaknesses. We will present and evaluate several techniques that have been applied in providing evidence for the orchestration of the biosynthetic pathways of cyanogenic glucosides and glucosinolates in metabolons. These evolutionarily related pathways have ER-localized cytochromes P450 that are proposed to function as anchoring site for assembly of the enzymes into metabolons. Additionally, we have included commonly used techniques, even though they have not been used (yet) on these two pathways. In the review, special attention will be given to less-exploited fluorescence-based methods such as FCS and FLIM. Ultimately, understanding the orchestration of biosynthetic pathways may contribute to successful engineering in heterologous hosts.     

The shape of things to come in the study of the origin of species?

Perhaps Darwin would agree that speciation is no longer the mystery of mysteries that it used to be. It is now generally accepted that evolution by natural selection can contribute to ecological adaptation, resulting in the evolution of reproductive barriers and, hence, to the evolution of new species (Schluter & Conte 2009 ; Meyer 2011 ; Nosil 2012 ). From genes that encode silencing proteins that cause infertility in hybrid mice (Mihola et al. 2009 ), to segregation distorters linked to speciation in fruit flies (Phadnis & Orr 2009 ), or pollinator‐mediated selection on flower colour alleles driving reinforcement in Texan wildflowers (Hopkins & Rausher 2012 ), characterization of the genes that drive speciation is providing clues to the origin of species (Nosil & Schluter 2011 ). It is becoming apparent that, while recent work continues to overturn historical ideas about sympatric speciation (e.g. Barluenga et al. 2006 ), ecological circumstances strongly influence patterns of genomic divergence, and ultimately the establishment of reproductive isolation when gene flow is present (Elmer & Meyer 2011 ). Less clear, however, are the genetic mechanisms that cause speciation, particularly when ongoing gene flow is occurring. Now, in this issue, Franchini et al. ( 2014 ) employ a classic genetic mapping approach augmented with new genomic tools to elucidate the genomic architecture of ecologically divergent body shapes in a pair of sympatric crater lake cichlid fishes. From over 450 segregating SNPs in an F2 cross, 72 SNPs were linked to 11 QTL associated with external morphology measured by means of traditional and geometric morphometrics. Annotation of two highly supported QTL further pointed to genes that might contribute to ecological divergence in body shape in Midas cichlids, overall supporting the hypothesis that genomic regions of large phenotypic effect may be contributing to early‐stage divergence in Midas cichlids.     

How often does the myristoylated N-terminal latch of c-Abl come off?

The myristoylated N-terminal latching to the C-terminal lobe of c-Abl was recently demonstrated to be an important regulatory element for the kinase, playing a role similar to that of the tyrosine-phosphorylated C-terminal tail of c-Src. A potential mechanism for activating c-Abl is the dissociation of the myristoylated N-terminal latch. How often does this latch spontaneously come off? A recent theoretical model along with the experimental results of Superti-Furga, Kuriyan, and co-workers suggests that the equilibrium fraction of c-Abl in which the myristoylated N-terminal is unlatched is approximately 0.5%.     

Is increased juvenile infection the key to recovery of wild rabbit populations from the impact of rabbit haemorrhagic disease?

The frequency and timing of rabbit haemorrhagic disease (RHD) epizootics and their impact on different age groups of rabbits were studied for 15 years in a recovering rabbit population in South Australia. We recorded the number and body size of rabbits dying during RHD epizootics, collected tissue for genetic analysis of rabbit haemorrhagic disease virus variants and compared the number of carcasses found to the number of susceptible rabbits present at the beginning of each epizootic. All RHD epizootics occurred between late winter and spring, but, progressively, epizootics started earlier and became more frequent and prolonged, fewer susceptible adult rabbits were present during epizootics, and the age of rabbits dying of RHD declined. Increased infection and virus shedding in juvenile rabbits offers the most plausible explanation for those epidemiological changes; the disease is now increasingly transmitted through populations of kittens, starting before young-of-the-year reach adult size and persisting late in the breeding season, so that most rabbits are challenged in their year of birth. These changes have increased juvenile mortality due to RHD but reduced total mortality across all age groups, because age-specific mortality rates are lower in young rabbits than in older rabbits. We hypothesise that this may be the proximate cause of recovery in rabbit populations across Australia and possibly elsewhere.     

Where will the wood come from? Plantation forests and the role of biotechnology

Wood is almost as important to humanity as food, and the natural forests from which most of it is harvested from are of enormous environmental value. However, these slow-growing forests are unable to meet current demand, resulting in the loss and degradation of forest. Plantation forests have the potential to supply the bulk of humanity's wood needs on a long-term basis, and so reduce to acceptable limits the harvest pressures on natural forests. However, if they are to be successful, plantation forests must have a far higher yield of timber than their natural counterparts, on much shorter rotation times. To achieve this in reasonable time, biotechnology must be applied to the tree-improvement process, for which large increases in public and private capital investment are needed. However, additional obstacles exist in the form of opposition to plantations, some forest ecocertification schemes, and concerns about aspects of forest biotechnology, especially genetic engineering. It is the intention of this article to explain, in detail, why plantation forests are needed to sustainably meet the world's demand for wood, why they are not being developed fast enough, and why the application of biotechnology to tree improvement is essential to speeding up this process.     

How to determine the susceptibility of Meligethes aeneus to neonicotinoids?

Three different bioassays were used to determine the susceptibility to the neonicotinoid Biscaya^® of oilseed rape pollen beetles collected from fields in Bavaria. The one in which the test substance was applied to the inner wall of glass tubes is recommended for future studies on pollen beetles because it is not dependent on the availability of plant material and provides precise information on the amount of insecticide required per unit area.     

Early Evolution of Membrane Lipids: How did the Lipid Divide Occur?

The ubiquitous distribution, homology over three domains, and key role in the membrane formation of the enzymes of the CDP-alcohol phosphatidyltransferase family, as well as phylogenetic analyses of lipid synthesizing enzymes suggest that the membranes of Wächtershäuser’s hypothetical pre-cells (universal common ancestor) [Mol Microbiol 47:13–22 (2003)] comprised a lipid bilayer with four types of core lipids [G-1-P-isoprenoid ether (Ai), G-3-P-fatty acyl ester (Bf), G-1-P-fatty acyl ester (Af) and G-3-P-isoprenoid ether (Bi)]. Here, a complementary hypothesis is presented to explain the difference between archaeal and bacterial lipids (lipid divide). The main driving force of lipid segregation is assumed to be glycerophosphate (GP) enantiomers, as Wächtershäuser proposed, but in the present study the hydrocarbon chains bound to each backbone are also hypothesized to affect lipid segregation. It is assumed that segregation was stimulated by different hydrocarbon chains bound to different GP backbones (Ai:Bf or Af:Bi). Because Ai and Bi are diastereomers and Af and Bf are enantiomers, Ai:Bf and Af:Bi are not equivalent. G-1-P-isoprenoid ether is provisionally assumed to segregate more easily from Bf than Bi does from Af. G-1-P-isoprenoid ether and Bf could more easily achieve the more stable homochiral membranes that are the ancestors of Archaea and Bacteria. This can explain why the extant archaeal and bacterial membrane lipids are mainly composed by Ai and Bf lipids, respectively. Because polar head groups were localized in the cytoplasmic compartment of pre-cells, they were equally carried over to Archaea and Bacteria during differentiation. Consequently, the both descendants shared the main head groups of membrane phospholipids.     

How to use the paradigm of ischemic preconditioning to protect the heart?

Ischemic preconditioning affords the most powerful protection to a heart submitted to a prolonged ischemia-reperfusion. During the past decade, a huge amount of work allowed to better understand the features of this protective effect as well as the molecular mechanisms. Ischemic preconditioning reduces infarct size and improves functional recovery; its effects on arrhythmias remain debated. Triggering of the protection involves cell surface receptors that activate pro-survival pathways including protein kinase C, PI3-kinase, possibly Akt and ERK1/2, whose downstream targets remain to be determined. Much attention has been recently focused on the role of mitochondrial K(+)ATP channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury. Based on these experimental studies attempts have been made to transfer preconditioning from bench to bedside. Human experimental models of ischemic preconditioning have been set up, including cardiac surgery, coronary angioplasty or treadmill exercise, to perform pathophysiological studies. Yet, protecting the heart of CAD (coronary artery disease) patients requires a pharmacological approach. The IONA trial has been an example of the clinical utility of preconditioning. It helped to demonstrate that chronic administration of nicorandil, a K(+)ATP opener that mimics ischemic preconditioning in experimental preparations, improves the cardiovascular prognosis in CAD patients. Recent experimental studies appear further encouraging. It appears that "postconditioning" the heart (i.e. performing brief episodes of ischemia-reperfusion at the time of reperfusion) is as protective as preconditioning. In other words, a therapeutic intervention performed as late as at the time of reflow can still significantly limit infarct size. Further work is needed to determine whether this may be transferred to the clinical practice.