Ever wondered how does anybody know that
ATGCCACTTGACTAATGCC
doesn’t originally belong my organism but
ATGTAACGGTAACCATGA
does?
In other words, how do you know that a gene has been horizontally acquired?
Well, as far as I know, there are several ways of knowing that:

1) Location of our gene or cluster of genes
For instance if our gene is located close to a tRNA ( hot-spot for insertions) and has mobile elements surrounding it-> then you have 1 point in the acquired-o-meter

2)Incongruent phylogenetic trees
So if I build a phylogenetic tree of my protein or gene in question together with some other homologous genes and I compare it with the 16s rRNA tree of the species included in the analysis and they don’t match we have another big point in our acquired-o-meter. For instance, if my gene encoding gorilate decaiguasilase from E. coli is clustering with streptococci and other gram positives, then you should be happy (provided that many other things are right too, but I don’t want to bring you down now…).

3)Aberrant G+C content
Each microorganism has its own G+C content, and it remains pretty constant across the genome (to a certain extent), so if my bug has, say E. coli, 50% G+C content and my possibly foreign DNA has 40% of G+C, it is highly unlikey that this group of genes belong to E. coli. So… another point in the acquired-o-meter

4)There are other ways of finding out whether my gene’s been acquired or not, I’ll explain them next week:
Genomic signature
Codon and amino acid usage

If you wanna know more about this, a very good and summarized paper is: Samuel Karlin’s “Detecting anomalous gene clusters and pathogenicity islands in diverse bacterial genomes” Trends in Microbiology, 2001.

Hope this might be helpful