Cosmid

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A cosmid is a type of hybrid plasmid that contains a Lambda phage cos sequence.^[1] Often used as cloning vectors in genetic engineering, cosmids can be used to build genomic libraries. They were first described by Collins and Hohn in 1978.^[2] Cosmids can contain 37 to 52 (normally 45) kb of DNA, limits based on the normal bacteriophage packaging size. They can replicate as plasmids if they have a suitable origin of replication (ori): for example SV40 ori in mammalian cells, ColE1 ori for double-stranded DNA replication, or f1 ori for single-stranded DNA replication in prokaryotes. They frequently also contain a gene for selection such as antibiotic resistance, so that the transformed cells can be identified by plating on a medium containing the antibiotic. Those cells which did not take up the cosmid would be unable to grow.^[3]

Unlike plasmids, they can also be packaged in vitro into phage capsids, a step which requires cohesive ends, also known as cos sites also used in cloning with a lambda phage as a vector, however nearly all the lambda genes have been deleted with the exception of the cos sequence. The hybrid cosmid DNA in the capsids can then be transferred into bacterial cells by transduction. Since there is a requirement for in vitro packaging whereby at least 38 kb of DNA is required between the cos sites, the vector without insert DNA will not be packaged (plasmids instability is increased if the novel inserted DNA contains many direct repeats or palindromic (inverted repeats) DNA. This instability can largely be counteracted by using a host bacterium with specific mutations affecting DNA recombination (N.B. Absence of inverted repeats was noted in the first Hohn & Collins publication cited above; see also^[4]).