Plasmids are ubiquitous mobile elements that serve as a pool of many host 
beneficial traits such as antibiotic resistance in bacterial communities. To 
understand the importance of plasmids in horizontal gene transfer, we need to 
gain insight into the 'evolutionary history' of these plasmids, i.e. the range 
of hosts in which they have evolved. Since extensive data support the proposal 
that foreign DNA acquires the host's nucleotide composition during long-term 
residence, comparison of nucleotide composition of plasmids and chromosomes 
could shed light on a plasmid's evolutionary history. The average absolute 
dinucleotide relative abundance difference, termed delta-distance, has been 
commonly used to measure differences in dinucleotide composition, or 'genomic 
signature', between bacterial chromosomes and plasmids. Here, we introduce the 
Mahalanobis distance, which takes into account the variance-covariance structure 
of the chromosome signatures. We demonstrate that the Mahalanobis distance is 
better than the delta-distance at measuring genomic signature differences 
between plasmids and chromosomes of potential hosts. We illustrate the 
usefulness of this metric for proposing candidate long-term hosts for plasmids, 
focusing on the virulence plasmids pXO1 from Bacillus anthracis, and pO157 from 
Escherichia coli O157:H7, as well as the broad host range multi-drug resistance 
plasmid pB10 from an unknown host.