Why do some coronaviruses become pandemic threats when others do not?

Despite multiple spillover events and short chains of transmission on at least 4 continents, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has never triggered a pandemic. By contrast, its relative, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has, despite apparently little, if any, previous circulation in humans. Resolving the unsolved mystery of the failure of MERS-CoV to trigger a pandemic could help inform how we understand the pandemic potential of pathogens, and probing it underscores a need for a more holistic understanding of the ways in which viral genetic changes scale up to population-level transmission.

What does it take for a coronavirus to become a pandemic threat? And why has MERS-CoV repeatedly failed to emerge as a pandemic pathogen when SARS-CoV-2 has successfully spread around the world?     

Finding a match: how do homologous sequences get together for recombination?

Decades of research into homologous recombination have unravelled many of the details concerning the transfer of information between two homologous sequences. By contrast, the processes by which the interacting molecules initially colocalize are largely unknown. How can two homologous needles find each other in the genomic haystack? Is homologous pairing the result of a damage-induced homology search, or is it an enduring and general feature of the genomic architecture that facilitates homologous recombination whenever and wherever damage occurs? This Review presents the homologous-pairing enigma, delineates our current understanding of the process and offers guidelines for future research.     

How do meiotic chromosomes meet their homologous partners?: lessons from fission yeast

Homologous chromosome pairing is required for proper chromosome segregation and recombination during meiosis. The mechanism by which a pair of homologous chromosomes contact each other to establish pairing is not fully understood. When pairing occurs during meiotic prophase in the fission yeast, Schizosaccharomyces pombe, the nucleus oscillates between the cell poles and telomeres remain clustered at the leading edge of the moving nucleus. These meiosis-specific activities produce movements of telomere-bundled chromosomes. Several lines of evidence suggest that these movements facilitate homologous chromosome pairing by aligning homologous chromosomes and promoting contact between homologous regions. Since telomere clustering and nuclear or chromosome movements in meiotic prophase have been observed in a wide range of eukaryotic organisms, it is suggested that telomere-mediated chromosome movements are general activities that facilitate homologous chromosome pairing.     

Genes for two homologous G-protein α subunits map to different human chromosomes

Summary Signal transduction across biological membranes is modulated by a family of related GTP-binding proteins termed G proteins. These G proteins have a heterotrimeric structure composed of α, β, and γ subunits. The α subunits of the G proteins bind GTP and appear to determine the biochemical specificity of the protein. We have recently cloned and characterized cDNA encoding two G-protein α subunits, α_i and α_h. The former is a substrate for ADP-ribosylation by pertussis toxin. The protein corresponding to α_h has not yet been identified. These cDNAs encode proteins, which demonstrate 90% sequence identity to one another and also show marked similarity to other G proteins. The present studies were designed to determine whether the genes for these related proteins are clustered on a single human chromosome. Genomic DNA isolated from a panel of mouse-human hybrid cell lines was analyzed by hybridization to cDNAs for α_i and α_h. Based on the distribution patterns of α_i and α_h in cell hybrids, the gene for α_i was assigned to human chromosome 7, and the gene for α_h assigned to chromosome 12. These data suggest that the G-protein gene family may be distributed over at least two human chromosomes.     

Improving enzyme properties: when are closer mutations better?

Study of mutations that improve enzyme properties reveals that in many, but not all, cases closer mutations are more effective than distant ones. For enantioselectivity, substrate selectivity and new catalytic activity (catalytic promiscuity) closer mutations improved enzymes more effectively than distant ones. However, both close and distant mutations can improve activity, thermal stability and also probably stability toward organic solvents. Typical random mutagenesis methods, such as error-prone PCR, create greater numbers of distant mutations than close mutations because enzymes contain more amino acids distant from the active site than close to the active site. This suggests that instead of mutating the entire enzyme, focusing mutations near the substrate-binding site might dramatically increase the success rate in many directed evolution experiments.     

Optimality modeling and fitness trade‐offs: when should plants become pollinator specialists?

The assumption that flowers readily evolve specializations for pollination by particular animals has been central to a standard view of pollinator-mediated adaptive divergence in angiosperms. Stebbins' Most Effective Pollinator Principle (MEPP) formalized this assumption in proposing that a plant should always evolve specializations to its most effective pollinator. I argue that the MEPP and its corollaries are unsupported by basic models of phenotypic selection which predict that a plant should evolve greater specialization to a particular pollinator when the marginal fitness gain exceeds the marginal fitness loss from becoming less adapted to all other pollinators. Differences in pollinator effectiveness are neither necessary nor sufficient to predict specialization. Differences in effectiveness certainly can foster floral specialization to the most effective pollinator in some cases, but when adaptation to a relatively ineffective pollinator requires little loss in the fitness contribution of a more effective pollinator, plants may exhibit striking specializations for the less effective pollinator. Recognizing that the effectiveness of pollinators is not tightly coupled to their importance in selecting for phenotypic novelty may resolve the mismatch between floral features that appear to represent clear evolutionary responses to specific pollinators and patterns of flower visitation that often seem generalized. To shed light on agents of selection and the adaptive value of floral traits I argue that we must go beyond measures of pollinator effectiveness to investigate pollinator-mediated fitness trade-offs over a range of floral phenotypes.     

Thermal preference: when does an asset become a liability?

Synopsis Most fish species (and sometimes different life stages within a species) exhibit behavioral temperature selection. In nature, thermal gradients provide habitat structure to which fish orient. Apparently, fish have evolved to fit into thermal niches to optimize physiological, ecological, and reproductive performance in their native habitats. However, man has perturbed many of these habitats to the point where previously advantageous thermal preference behavior may now be inappropriate. Thermal perturbations are the most obviously related examples of man's interference, but a fish's inherent thermal preference behavior can also magnify the biological effects of changes in dissolved oxygen, food supply, toxicants, and physical barriers. Environmental management should (1) consider thermal preference behavior when evaluating habitat suitability, (2) manage for needed temperature and thermal structure, and (3) give priority attention to minimizing degradation of preferred thermal habitat, especially when it is in short supply.     

Paleopediatrics: Or when did human infants really become human?

Modern human children take about twice as long as their closest biological relative, the chimpanzee, to mature. One standard explanation for the evolution of “delayed maturation” at an early stage of human evolution is that it provided the time necessary for immature individuals to learn complex skills, most notably those relating to tool-making abilities. However, after comparing dental maturational profiles of early hominids from South Africa (who apparently did make and use stone tools) (Susman [1994] Science 265:1570–1573) to those of extant humans and chimpanzees, we find no evidence to document an association between “delayed maturation” and tool-making abilities in the early stages of human evolution. This also suggests that the assumed association between prolonged childhood dependency and other behaviors often associated with the advent of tool-making such as cooperative hunting, food sharing, home bases, sexual division of labor, etc., is also suspect. Instead, we must look for other, or additional, selective pressures for the evolution of “delayed maturation,” which may postdate the australopithecine radiation. © 1995 Wiley-Liss, Inc.     

Are dendrites in Drosophila homologous to vertebrate dendrites?

Dendrites represent arborising neurites in both vertebrates and invertebrates. However, in vertebrates, dendrites develop on neuronal cell bodies, whereas in higher invertebrates, they arise from very different neuronal structures, the primary neurites, which also form the axons. Is this anatomical difference paralleled by principal developmental and/or physiological differences? We address this question by focussing on one cellular model, motorneurons of Drosophila and characterise the compartmentalisation of these cells. We find that motorneuronal dendrites of Drosophila share with typical vertebrate dendrites that they lack presynaptic but harbour postsynaptic proteins, display calcium elevation upon excitation, have distinct cytoskeletal features, develop later than axons and are preceded by restricted localisation of Par6-complex proteins. Furthermore, we demonstrate in situ and culture that Drosophila dendrites can be shifted from the primary neurite to their soma, i.e. into vertebrate-like positions. Integrating these different lines of argumentation, we propose that dendrites in vertebrates and higher invertebrates have a common origin, and differences in dendrite location can be explained through translocation of neuronal cell bodies introduced during the evolutionary process by which arthropods and vertebrates diverged from a common urbilaterian ancestor. Implications of these findings for studies of dendrite development, neuronal polarity, transport and evolution are discussed.     

What to do, or how to do it?

In this issue of Neuron, Ajemian et al. present a computational model of the activity of neurons in primary motor cortex (M1) during isometric movements in different postures. By modeling the output of M1 neurons in terms of their influence on muscles, they find each M1 neuron maps its output into a particular pattern of muscle actions.     

Will tuberculosis become resistant to all antibiotics?

The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug efficacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9-64.3%), close to the 6.3% (range 0-28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9%) and 1.0% (range 0-14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative fitness of drug-resistant strains.     

Naturally SIV-infected sooty mangabeys: are we closer to understanding why they do not develop AIDS?

Simian immunodeficiency viruses (SIV) infection of sooty mangabey (SM) monkeys (Cercocebus atys), a natural host species, does not induce CD4+ T cell depletion and acquired immunodeficiency syndrome (AIDS) despite chronic high levels of virus replication. In contrast, SIV infection of non-natural host species, such as rhesus macaques (RM), induces a disease that closely resembles AIDS in humans. The mechanisms underlying the lack of disease progression in SIV-infected SMs are incompletely understood, but certainly reflect a complex evolutionary adaptation whereby the host immune system is not significantly damaged by the highly replicating virus. It is now widely recognized that a better understanding of these mechanisms may provide clues to the pathogenesis of immunodeficiency in HIV-infected humans. In this article I discuss five different hypotheses that may account for the non-pathogenic course of infection in SIV-infected SMs and briefly review the available data supporting each of these hypotheses.     

Inevitability or contingency: how many chromosomes do we really need?

<正>In an essay written by the evolutionary biologist Theodosius Dobzhansky in 1973, he pointed out that "Nothing in Biology Makes Sense Except in the Light of Evolution." An interesting phenomenon in biology is the presence of variable numbers of chromosomes in different organisms. Besides several species, which possess multiple circular chromosomes or simply linear chromosomes (Baril et al.1989; Suwanto and Kaplan, 1989; Jumas-Bilak et al., 1998),most prokaryotes only possess one circular chromosome. In contrast, the genomes of eukaryotic species are usually packaged into linear chromosomes with numbers varying     

Transformation: how do nematode sperm become activated and crawl?

Nematode sperm undergo a drastic physiological change during spermiogenesis (sperm activation). Unlike mammalian flagellated sperm, nematode sperm are amoeboid cells and their motility is driven by the dynamics of a cytoskeleton composed of major sperm protein (MSP) rather than actin found in other crawling cells. This review focuses on sperm from Caenorhabditis elegans and Ascaris suum to address the roles of external and internal factors that trigger sperm activation and power sperm motility. Nematode sperm can be activated in vitro by several factors, including Pronase and ionophores, and in vivo through the TRY-5 and SPE-8 pathways. Moreover, protease and protease inhibitors are crucial regulators of sperm maturation. MSP-based sperm motility involves a coupled process of protrusion and retraction, both of which have been reconstituted in vitro. Sperm motility is mediated by phosphorylation signals, as illustrated by identification of several key components (MPOP, MFPs and MPAK) in Ascaris and the characterization of GSP-3/4 in C. elegans.