The problem is that those nucleotide sequences are embedded in an enormous genome.

The development of recombinant DNA technology provided a solution to this isolation problem.
Over the past thirty years this technology has matured into a powerful analytical tool which finds application in a diverse set of scientific disciplines ranging from ecology and evolution to mathematics and information science. It is this broad applicability that makes this technology so important to your undergraduate education.

Recombinant DNA technology originated with the collaboration between biochemists and geneticists to understand the Central Dogma. A favorite model system of the time was the prokaryote E. coli and its attendant bacteriophage. Among the phenomena being studied was that of

a lambda phage stock grown on one strain of E. coli (strain B) infects that strain with high efficiency.

This same phage stock infects a second E. coli strain R with very low efficiency (1 in 20³ plaques grow)

Recovery and re-titreing of progeny phage from one of these rare plaques shows that they infect the R strain with high efficiency, but infect the B strain with very low efficiency (1 in 20³ plaques grow)

Recovery and re-titreing of progeny phage from one of these rare plaques shows the same phenomena described above.

Phage grown in one strain infect that strain with high efficiency but infect the other strain with low efficiency.

Host restriction turned out to be a bacterial analog of an immune system allowing bacteria to recognize and defend themselves against foreign invaders (DNA molecules).

Host restriction is a two component system consisting of

When the phage injects its genome into an unfamiliar host on infection, the host's restriction enzymes recognize the phage DNA as foreign and break it into smaller linear pieces which are subsequently degraded by host exonucleases.

Well, thats a nice story, but how do these restriction enzymes recognize the host's genome as self and avoid degrading the heritable information store encoded therein?

When a phage is grown for several generations in a given host, the progeny phage acquire the methylation pattern specific to the hosts modification enzyme. These progeny phage evade the hosts 'immune system' since their genomes are not recognizable as foreign by the hosts restriction enzymes (it has the hosts self-methylation pattern).

When these progeny phage infect a second host strain, the phage genome is immediately recognized by the second host's restriction enzymes and degraded as it lacks the new hosts specific methylation pattern.

So where do the rare plaques come from (the 1 in 10³ plaques that grow on the new host)?

We can envision two types of methylation events.

The first involves the methylation of host genome sequences after they have replicated.
(if necessary, go back and review DNA replication in your text)
The two daughter genome molecules contain one methylated strand (the parental template strand) and one newly synthesized strand .
These hemi-methylated sites are very efficiently methylated by the host modification enyzmes.