Cosmid

A cosmid is a type of artificial plasmid vector used in gene cloning. Cosmids contain a cos sequence, a DNA sequence originally from the lambda (λ) bacteriophage, which allows the cosmid to be packaged into lambda phage particles for efficient infection of Escherichia coli (E. coli) cells.

Mechanism and Use:

The cos sequence is crucial for in vitro packaging of DNA into phage heads. During the construction of a cosmid library, large fragments of foreign DNA (typically 37-45 kb) are ligated into a cosmid vector that has been linearized. This recombinant DNA molecule, containing the cos sequence, can then be packaged into a bacteriophage lambda particle. These particles infect E. coli with high efficiency, delivering the cosmid DNA into the bacterial cell. Once inside the bacteria, the cosmid circularizes (again, facilitated by the cos sequence) and replicates as a plasmid.

Advantages of Using Cosmids:

• Large Insert Size: Cosmids can carry much larger DNA fragments compared to typical plasmids, making them useful for cloning entire genes or large segments of eukaryotic DNA.
• Efficient Transformation: The use of lambda phage particles to deliver the DNA results in a much higher transformation efficiency than standard plasmid transformation methods, especially for larger DNA fragments.

Limitations:

• Insert Size Limit: While larger than plasmids, there's still an upper limit to the size of DNA that can be effectively packaged into the phage head.
• Instability: Very large inserts can sometimes be unstable and prone to rearrangements within the bacterial host.

Applications:

Cosmids were widely used in the past for constructing genomic libraries, particularly before the advent of Bacterial Artificial Chromosomes (BACs) and Yeast Artificial Chromosomes (YACs) which can accommodate even larger DNA inserts. They are still valuable tools for cloning and manipulating large genes or gene clusters in certain research applications.