The optogenetic (r)evolution

Optogenetics is a rapidly evolving field of technology that allows optical control of genetically targeted biological systems at high temporal and spatial resolution. By heterologous expression of light-sensitive microbial membrane proteins, opsins, cell type-specific depolarization or silencing can be optically induced on a millisecond time scale. What started in a petri dish is applicable today to more complex systems, ranging from the dissection of brain circuitries in vitro to behavioral analyses in freely moving animals. Persistent technical improvement has focused on the identification of new opsins, suitable for optogenetic purposes and genetic engineering of existing ones. Optical stimulation can be combined with various readouts defined by the desired resolution of the experimental setup. Although recent developments in optogenetics have largely focused on neuroscience it has lately been extended to other targets, including stem cell research and regenerative medicine. Further development of optogenetic approaches will not only highly increase our insight into health and disease states but might also pave the way for a future use in therapeutic applications.     

The (r)evolution of cancer genetics

The identification of an increasing number of cancer genes is opening up unexpected scenarios in cancer genetics. When analyzed for their systemic properties, these genes show a general fragility towards perturbation. A recent paper published in BMC Biology shows how the founder domains of known cancer genes emerged at two macroevolutionary transitions - the advent of the first cell and the transition to metazoan multicellularity.     

Boosters for adeno-associated virus (AAV) vector (r)evolution

Adeno-associated virus (AAV) is one of the most exciting and most versatile templates for engineering of gene-delivery vectors for use in human gene therapy, owing to the existence of numerous naturally occurring capsid variants and their amenability to directed molecular evolution. As a result, the field has witnessed an explosion of novel “designer” AAV capsids and ensuing vectors over the last two decades, which have been isolated from comprehensive capsid libraries generated through technologies such as DNA shuffling or peptide display, and stratified under stringent positive and/or negative selection pressures. Here, we briefly highlight a panel of recent, innovative and transformative methodologies that we consider to have exceptional potential to advance directed AAV capsid evolution and to thereby accelerate AAV vector revolution. These avenues comprise original technologies for (i) barcoding and high-throughput screening of individual AAV variants or entire capsid libraries, (ii) selection of transduction-competent AAV vectors on the DNA level, (iii) enrichment of expression-competent AAV variants on the RNA level, as well as (iv) high-resolution stratification of focused AAV capsid libraries on the single-cell level. Together with other emerging AAV engineering stratagems, such as rational design or machine learning, these pioneering techniques promise to provide an urgently needed booster for AAV (r)evolution.     

Genetic characteristics and protective properties of neamin-resistant mutant Salmonella typhimurium and S. dublin of the Nea(r) Str(s) and Nea(r) Str(r) 500 classes

The genetic analysis of attenuated mutants, class Nea(r) Str(s), with the use of bacteriophage P 22 has shown that mutation rendering the mutants resistant to neamine is localized in gene nea A. In experiments with the intraperitoneal infection of mice, the appearance of this mutation in S. typhimurium and S. dublin virulent strains has been found to lead to the decrease of virulence in 100% of clones. On the basis of the data obtained in this investigation, region str-spc in S. typhimurium and S. dublin has been mapped. In contrast to mutation spc A, mutations nea A and str A have been shown to inhibit the action of amber suppressor. The investigation has confirmed the regularity, previously established for Shigella flexneri, concerning the relationship between the influence of mutations, occurring in the genes which determine resistance to neamine and streptomycin and control the synthesis of ribosomal proteins S4, S5, S12 and S17, on the virulence of S. typhimurium and S. dublin and the effect of these mutations on the accuracy of the translation of genetic information in the biosynthesis of protein: mutation spc A has been found to produce no changes in the virulence of salmonellae, while mutations nea A and str A cause its loss. Salmonella strains carrying mutations nea A and nea B have shown pronounced protective properties in experiments on mice.     

The human platelet receptor(s) for quinine/quinidine-dependent antibodies

Substantial evidence now exists to associate platelet membrane glycoprotein Ib (GP Ib) with a receptor for quinine/quinidine-dependent platelet-specific antibodies. A direct relationship between GP Ib and this receptor activity has been difficult to establish for several reasons, including: the apparent existence of additional receptor activity not directly attributable to the presence of GP Ib; the variable reactivity of different sera observed by some investigators; the instability of receptor activity in semi-purified, soluble form; and differences in methods used by various laboratories to identify and quantitate either quinine/quinidine-dependent antibodies or platelet receptor activity. Moreover, little attention has been paid to the possibility that the Bernard-Soulier syndrome may represent a more heterogeneous collection of functional and molecular platelet abnormalities than hitherto supposed. As more patients are identified and studied, this possibility can also be addressed. A role for factor VIII-related antigen (VIIIR:Ag) in platelet destruction and/or clearance by drug-antibody complexes remains controversial. The observation that VIIIR:Ag is required for platelet activation in vitro (serotonin release, aggregation and increased platelet factor 3 availability) has been made, yet recent evidence indicates that VIIIR:Ag is not required for binding of antibody to platelets in the presence of drug or for complement-mediated lysis of platelets by antibody and drug. Evidence that VIIIR:Ag participates as part of the initial immunogenic complex is intriguing, yet still unconfirmed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Origin(s), evolution,and systematics ofCucurbita pepo (Cucurbitaceae)

Numerical studies of morphological data and starch gel electrophoresis have provided a new perspective on important issues pertinent to the origin(s) and subsequent evolution of domesticatedCucurbita pepo. Wild C.texana and/orC. fraterna appear to be the most likely candidates for progenitor(s) of the domesticate. Populations of texana-like plants from beyond Texas share various attributes with Texas populations, suggesting that C. texana once had a more widespread distribution to the northeast. The possibility exists thatC. pepo was domesticated independently in eastern U.S., as well as in Mexico, which is in line with recent archeological findings. Multiple domestications are also supported by allozyme data indicating a substantial divergence within the species. A new classification consisting of C.pepo ssp.pepo (origins in Mexico),C. pepo ssp.ovifera var. ovifera (origins in eastern U.S.), and C.pepo ssp.ovifera var. texana (spontaneous populations in eastern U.S.) is proposed.     

Human brain evolution: harnessing the genomics (r)evolution to link genes, cognition, and behavior

The evolution of the human brain has resulted in numerous specialized features including higher cognitive processes such as language. Knowledge of whole-genome sequence and structural variation via high-throughput sequencing technology provides an unprecedented opportunity to view human evolution at high resolution. However, phenotype discovery is a critical component of these endeavors and the use of nontraditional model organisms will also be critical for piecing together a complete picture. Ultimately, the union of developmental studies of the brain with studies of unique phenotypes in a myriad of species will result in a more thorough model of the groundwork the human brain was built upon. Furthermore, these integrative approaches should provide important insights into human diseases.     

The evolution of Strepsiptera (Hexapoda)

An evolutionary scenario for the enigmatic group Strepsiptera is provided, based on the results of a comprehensive cladistic analysis of characters of all life stages. A recently described fossil--+Protoxenos janzeni--the most archaic strepsipteran, sheds new light on the early evolution of the group and reduces the "morphological gap" between Strepsiptera and other insects. It weakens both current hypotheses--Coleoptera+Strepsiptera and Diptera+Strepsiptera (="Halteria"). The splitting into +Protoxenos (Protoxenidae) and the remaining Strepsiptera was linked with a distinct size reduction and many morphological changes. Unlike males of extant strepsipteran species, +Protoxenos was still able to process food. Mengeidae (+Mengea), with two small species, is the sister group of extant Strepsiptera. A unique characteristic of extant males (Strepsiptera s. str.) is the mouthfield sclerite. It is part of an air uptake apparatus which belongs to an extremely modified air-filled "balloon gut". Besides this, male strepsipterans possess specialised antennae and compound eyes, a strongly developed flight apparatus, large testes, and a sperm pump, whereas other organ systems are strongly reduced (e.g., fat body, malpighian tubules). Males are designed to find females within a few hours and to copulate. A dramatic change is linked with the split into Mengenillidae and Stylopidia. The change to pterygote hosts and the permanent endoparasitism of the females are evolutionary novelties acquired by the latter clade, and linked with far-reaching morphological transformations, e.g. the presence of unique brood organs. Hairy tarsal adhesive devices are present in males and guarantee efficient attachment to the host during copulation. A well-founded clade within Stylopidia is Stylopiformia, which are characterised by a unique fissure-shaped birth opening. The evolutionary development towards the most specialised and successful forms (parasites of aculeate Hymenoptera [e.g., Xenidae+Stylopidae], ca. 46% of the species) is a stepwise process. The presented evolutionary scenario comprises a complex network of functionally correlated morphological changes in primary larvae, secondary larvae, females and males.     

The adaptive evolution database (TAED)

Background

The Master Catalog is a collection of evolutionary families, including multiple sequence alignments, phylogenetic trees and reconstructed ancestral sequences, for all protein-sequence modules encoded by genes in GenBank. It can therefore support large-scale genomic surveys, of which we present here The Adaptive Evolution Database (TAED). In TAED, potential examples of positive adaptation are identified by high values for the normalized ratio of nonsynonymous to synonymous nucleotide substitution rates (K_A/K_S values) on branches of an evolutionary tree between nodes representing reconstructed ancestral sequences.

Results

Evolutionary trees and reconstructed ancestral sequences were extracted from the Master Catalog for every subtree containing proteins from the Chordata only or the Embryophyta only. Branches with high K_A/K_S values were identified. These represent candidate episodes in the history of the protein family when the protein may have undergone positive selection, where the mutant form conferred more fitness than the ancestral form. Such episodes are frequently associated with change in function. An unexpectedly large number of families (between 10% and 20% of those families examined) were found to have at least one branch with high K_A/K_S values above arbitrarily chosen cut-offs (1 and 0.6). Most of these survived a robustness test and were collected into TAED.

Conclusions

TAED is a raw resource for bioinformaticists interested in data mining and for experimental evolutionists seeking candidate examples of adaptive evolution for further experimental study. It can be expanded to include other evolutionary information (for example changes in gene regulation or splicing) placed in a phylogenetic perspective.     

Relevance of connexin deafness (DFNB1) to human evolution

The connexins are the subunits of a family of proteins that form gap junctions, allowing ions and small molecules to move between adjacent cells. At least four connexins are expressed in the ear, and, although there are known mutations at >100 loci that can cause deafness, those involving DFNB1, in the interval 13q11-q12 containing the GJB2 and GJB6 genes coding for connexins 26 and 30, are the most frequent cause of recessive deafness in many populations. We have suggested that the combined effects of relaxed selection and linguistic homogamy can explain the high frequency of connexin deafness and may have doubled its incidence in this country during the past 200 years. In this report, we show by computer simulation that assortative mating, in fact, can accelerate dramatically the genetic response to relaxed selection. Along with the effects of gene drift and consanguinity, assortative mating also may have played a key role in the joint evolution and accelerated fixation of genes for speech after they first appeared in Homo sapiens 100,000-150,000 years ago.     

Collaboration and human social evolution: review of Michael Tomasello’s why we cooperate (MIT Press, 2009)

Michael Tomasello’s new book Why We Cooperate explores the ontogeny and evolution of human altruism and human cooperation, paying particular attention to how such behaviors allow humans to create social institutions.     

The human microbiome in evolution

The trillions of microbes living in the gut—the gut microbiota—play an important role in human biology and disease. While much has been done to explore its diversity, a full understanding of our microbiomes demands an evolutionary perspective. In this review, we compare microbiomes from human populations, placing them in the context of microbes from humanity’s near and distant animal relatives. We discuss potential mechanisms to generate host-specific microbiome configurations and the consequences of disrupting those configurations. Finally, we propose that this broader phylogenetic perspective is useful for understanding the mechanisms underlying human–microbiome interactions.     

The evolution of human sexuality

The study of human sexuality from the darwinian perspective is in an explosive phase. Recent research is diverse; for instance, the dynamics of heterosexual relationships, the role of honest advertisement in attractiveness, the role of fluctuating asymmetry in sexual competition, and sexual conflict over fertilization, seen in sperm competition adaptations of men and possible cryptic sire-choice adaptation of women. Also, recent research reveals that the sexual selection that designed human secondary sexual traits was functional rather than strictly fisherian.