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A semi-synthetic organism with an expanded genetic alphabet

Overview of attention for article published in Nature, May 2014
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Citations

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1483 Mendeley
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13 CiteULike
Title
A semi-synthetic organism with an expanded genetic alphabet
Published in
Nature, May 2014
DOI 10.1038/nature13314
Pubmed ID
Authors

Denis A. Malyshev, Kirandeep Dhami, Thomas Lavergne, Tingjian Chen, Nan Dai, Jeremy M. Foster, Ivan R. Corrêa, Floyd E. Romesberg

Abstract

Organisms are defined by the information encoded in their genomes, and since the origin of life this information has been encoded using a two-base-pair genetic alphabet (A-T and G-C). In vitro, the alphabet has been expanded to include several unnatural base pairs (UBPs). We have developed a class of UBPs formed between nucleotides bearing hydrophobic nucleobases, exemplified by the pair formed between d5SICS and dNaM (d5SICS-dNaM), which is efficiently PCR-amplified and transcribed in vitro, and whose unique mechanism of replication has been characterized. However, expansion of an organism's genetic alphabet presents new and unprecedented challenges: the unnatural nucleoside triphosphates must be available inside the cell; endogenous polymerases must be able to use the unnatural triphosphates to faithfully replicate DNA containing the UBP within the complex cellular milieu; and finally, the UBP must be stable in the presence of pathways that maintain the integrity of DNA. Here we show that an exogenously expressed algal nucleotide triphosphate transporter efficiently imports the triphosphates of both d5SICS and dNaM (d5SICSTP and dNaMTP) into Escherichia coli, and that the endogenous replication machinery uses them to accurately replicate a plasmid containing d5SICS-dNaM. Neither the presence of the unnatural triphosphates nor the replication of the UBP introduces a notable growth burden. Lastly, we find that the UBP is not efficiently excised by DNA repair pathways. Thus, the resulting bacterium is the first organism to propagate stably an expanded genetic alphabet.

Twitter Demographics

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Mendeley readers

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Geographical breakdown

Country Count As %
United States 58 4%
United Kingdom 15 1%
Germany 11 <1%
France 10 <1%
Canada 5 <1%
Japan 5 <1%
Italy 5 <1%
Russia 5 <1%
Spain 5 <1%
Other 44 3%
Unknown 1320 89%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 451 30%
Researcher 293 20%
Student > Bachelor 219 15%
Student > Master 175 12%
Student > Doctoral Student 61 4%
Other 284 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 670 45%
Biochemistry, Genetics and Molecular Biology 262 18%
Chemistry 220 15%
Unspecified 84 6%
Medicine and Dentistry 47 3%
Other 200 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 1712. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 September 2019.
All research outputs
#1,158
of 13,536,671 outputs
Outputs from Nature
#199
of 69,893 outputs
Outputs of similar age
#14
of 188,959 outputs
Outputs of similar age from Nature
#1
of 960 outputs
Altmetric has tracked 13,536,671 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 69,893 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 76.5. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 188,959 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 960 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.