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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 2016 Aug 30;113(35):9659–9660. doi: 10.1073/iti3516113

Reconstructing the emergence of a human coronavirus

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Dromedary camel. Image courtesy of Wikimedia Commons/Rusty Clark.

The Middle East respiratory syndrome coronavirus (MERS-CoV), which has triggered deadly epidemics, is thought to have originated in bats. However, the sources of most endemic human coronaviruses, which cause mild respiratory disease, remain unknown. Using targeted genetic screening, Victor Corman et al. (pp. 9864–9869) identified viruses related to HCoV-229E, a human coronavirus that causes the common cold, in nearly 6% of 1,033 dromedary camels previously screened for MERS in Saudi Arabia and Kenya. Phylogenetic comparison of bat, human, and camel 229E-like viruses suggested that the human 229E-like viruses likely stem from camels, similar to the causal agent of MERS. Live viruses isolated from camels successfully infected lab-grown human cells by latching onto the same enzymatic handhold that 229E uses to enter human cells. However, the camel viruses were as susceptible as human 229E to innate antiviral defense mediated by interferons. Further, tests using human immune sera against 229E revealed the existence of population-level immunity against the camel viruses, suggesting an attenuated risk of human epidemics. According to the authors, such fine-grained analysis of the origin of a human respiratory virus might offer insights into the evolution of MERS-CoV, a human pathogen that currently seems to lack the genetic wherewithal to spread consistently among people. — P.N

RNA synthesis by an RNA enzyme

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Amplification of RNA by RNA polymerase ribozyme.

Living organisms use protein-based enzymes to replicate and express genes, but primordial life is believed to have relied on RNA enzymes, or ribozymes, instead of proteins. Natural and synthetic ribozymes have been used to synthesize RNA in vitro, but their activity is limited to certain RNA sequences. David Horning and Gerald Joyce (pp. 9786–9791) used in vitro evolution to engineer a variant of the class I polymerase ribozyme with markedly improved activity. The authors selected randomized variants of the polymerase based on their ability to synthesize aptamers—RNA molecules that bind to specific target molecules—from a complementary RNA template. After 24 rounds of selection, the authors obtained a polymerase that could synthesize RNAs of varying sequence and structure, including cyanocobalamin and GTP aptamers, the F1 ligase ribozyme, and a yeast transfer RNA. The improved polymerase could also replicate short RNA templates in a protein-free form of the polymerase chain reaction that amplified RNA exponentially, achieving up to 40,000-fold amplification after 24 hours. The results suggest that gene replication and expression could be performed by RNA alone, and that combining and further improving these two functions might allow the creation of a synthetic form of RNA life, capable of self-sustained evolution, according to the authors. — B.D.

First land plants and oxygen levels

Diatomic oxygen first appeared in Earth’s atmosphere around 2.4 billion years ago in the Great Oxygenation Event. Although this shift steered the evolutionary path of life on Earth, the mechanism that increased oxygen to modern concentrations remains unexplained. Timothy Lenton et al. (pp. 9704–9709) propose that the emergence and evolution of land plants permanently increased organic carbon burial, driving up atmospheric oxygen toward present levels around 400 million years ago in a second oxygenation event that established a new dynamic steady state. Using an ecophysiological model of nonvascular plant species such as bryophytes and lichen, the authors show that the global net primary productivity (NPP) of Earth’s early plant biosphere could have accounted for roughly 30% of modern global terrestrial NPP by around 445 million years ago. The authors augment this finding to account for the higher carbon-to-phosphorous ratios of early bryophytes; recent findings suggest these plants selectively increased phosphorous weathering from rocks. The augmented model reproduces a trajectory consistent with the geochemical record, with the carbonate carbon isotope record increasing by approximately 2% around 445 million years ago and a corresponding rise in oxygen to modern levels by 420 to 400 million years ago, according to the authors. — T.J.

Collapse in European Neolithic populations

Anthropologists have uncovered numerous examples in which a thriving ancient society collapsed after a period of profound change. In sustainability science, ecosystem resilience—the ability of an ecosystem to absorb and rebound from disturbance—often ebbs prior to major collapse. However, resilience has proven difficult to quantify in the context of interconnected human social systems. Sean Downey et al. (pp. 9751–9756) examined whether tests of ecosystem resilience called early warning signals (EWS) can uncover trends during the European Neolithic, a period which began approximately 9,000 years ago, when new agricultural technologies triggered well-documented instances of widespread population growth followed by instability and dramatic collapse. Using a proxy that infers prehistoric population from temporal changes in the number of radiocarbon-dateable archaeological sites, the authors found that EWS statistical signatures of decreasing resilience can be detected well in advance of population declines. The authors also present computer simulations to eliminate sampling and taphonomic biases, atmospheric effects, and radiocarbon calibration error. According to the authors, EWS can be applied to archaeological studies and might help monitor and prevent collapse in extant human societies. — T.J.

Dietary practices of ancient hunter-gatherers

To evaluate ancient hunter-gatherer subsistence strategies, archaeologists typically analyze human and faunal remains or preserved residues associated with cooking-related activities. Because such proxies for ancient dietary practices are rare, Kyungcheol Choy et al. (pp. 9757–9762) conducted stable carbon and nitrogen isotopic analyses of residues in short-term hearths, a relatively common archaeological feature worldwide. Working at the Upward Sun River site in central Alaska, the authors examined 17 well-preserved hearths spanning three occupations between 13,200 to 11,500 years ago and entered the results in a stable isotope mixing model to estimate the relative contributions of marine, freshwater, and terrestrial sources. After verifying the output against zooarchaeological data, the model revealed that 11,800 and 11,500 years ago, these early Americans consumed aquatic animals, both freshwater and anadromous species, such as salmon. These dates represent the earliest known human use of anadromous salmon in the Americas. According to the authors, the study demonstrates that hearth residues can record the dietary trends and practices of mobile hunter-gatherers, particularly at sites where animal remains have not been preserved. — T.J.

Clathrin and B-cell physiology

The cytosolic protein clathrin forms clathrin-coated vesicles (CCVs), which control the uptake of membrane cargo and influence cell signaling processes. Shuang Wu et al. (pp. 9816–9821) investigated the contribution of clathrin light chain (CLC) subunits to the physiological function of clathrin in mice engineered to lack CLCa, the major CLC isoform in B lymphocytes. The lack of CLCa led to CLC deficiency in mouse B cells. Using fluorescent-activated cell sorting analysis, the authors found that mice lacking CLCa had a reduced number of germinal center (GC) B cells, but an elevated frequency of GC B cells that expressed the IgA antibody. The B-cell developmental defects were related to defects in internalization of certain growth factor and chemokine receptors, and the phenotype was likely due to increased receptor signaling caused by impaired endocytosis. Moreover, the study revealed that CLC depletion affected endocytosis of an opioid receptor, but not that of an adrenergic receptor, indicating that only a subset of signaling receptors depend on CLCs for endocytosis. Thus, CLC subunits play a role in the regulation and uptake of certain CCV cargo that can influence cell signaling pathways, and in turn, affect B-cell function and vertebrate physiology, according to the authors. — C.S.


Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

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