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.Recently scientists have achieved a feat the like of which has not been seen in billions of years, they have added new letters to the genetic alphabet of a living organism. What did they do? How did they do it ? Is it too good to be true? All these questions, and more await.
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)1, 2, 3. 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-amplified1 and transcribed4, 5 in vitro, and whose unique mechanism of replication has been characterized6, 7. 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.
We’ll be discussing it all at 8pm BST this Tuesday (27/05/14).
Follow the #microtwjc hashtag on Twitter to join in the discussion.
Full Paper with extended figures can be found here:
http://apinano.org.br/documentos/A-semi-synthetic-organism-with-an-expanded.pdf [edit- fixed the link- whoops!]
I hope to see you there !
We have a paper for this weeks MicroTWJC number 48…
The papers own significance statement is below. This is an interesting study with an important implication that should lead to a good discussion. See you all on Tues 6th May at 8 PM (British Time)
IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.
A small challenge for this week: Can you read this paper without the need to refer to the supplementary data?
UPDATE: You can find the storify of our conversation here –> Storify of #MicroTWJC number 48