august 30, 2016

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www.pnas.org/cgi/doi/10.1073/iti3516113 PNas | August 30, 2016 | vol. 113 | no. 35 | 9659–9660

Reconstructing the emergence of a human coronavirus

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. Phylo-genetic 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 epidem-ics. 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

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 syn-thetic 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 com-plementary RNA template. After 24 rounds of selec-tion, 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 poly-merase chain reaction that amplified RNA exponen-tially, 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

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

Amplification of RNA by RNA polymerase ribozyme.

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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 unex-plained. Timothy Lenton et al. (pp. 9704–9709) pro-pose 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 spe-cies 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 aug-ment 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 iso-tope 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 populationsAnthropologists have uncovered numerous exam-ples in which a thriving ancient society collapsed after a period of profound change. In sustainability science, ecosystem resilience—the ability of an eco-system to absorb and rebound from disturbance—often ebbs prior to major collapse. However, resilience has proven difficult to quantify in the con-text of interconnected human social systems. Sean Downey et al. (pp. 9751–9756) examined whether tests of ecosystem resilience called early warning sig-nals (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 dra-matic 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 com-puter simulations to eliminate sampling and tapho-nomic 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 archaeologi-cal 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 esti-mate 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 Amer-icans consumed aquatic animals, both freshwater and anadromous species, such as salmon. These dates represent the earliest known human use of anad-romous 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 physiologyThe cytosolic protein clathrin forms clathrin-coated vesicles (CCVs), which control the uptake of mem-brane 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 defi-ciency 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 adrener-gic receptor, indicating that only a subset of sig-naling 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 func-tion and vertebrate physiology, according to the authors. — C.S.

9660 | www.pnas.org/cgi/doi/10.1073/iti3516113 In this issue

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