The invention provides a method of tracking, identifying, and/or sorting
classes or subpopulations of molecules by the use of oligonucleotide
tags. Oligonucleotide tags of the invention each consist of a plurality
of subunits 3 to 6 nucleotides in length selected from a minimally
cross-hybridizing set. A subunit of a minimally cross-hybridizing set
forms a duplex or triplex having two or more mismatches with the
complement of any other subunit of the same set. The number of
oligonucleotide tags available in a particular embodiment depends on the
number of subunits per tag and on the length of the subunit. An important
aspect of the invention is the use of the oligonucleotide tags for
sorting polynucleotides by specifically hybridizing tags attached to the
polynucleotides to their complements on solid phase supports. This
embodiment provides a readily automated system for manipulating and
sorting polynucleotides, particularly useful in large-scale parallel
operations, such as large-scale DNA sequencing, mRNA fingerprinting, and
the like, wherein many target polynucleotides or many segments of a
single target polynucleotide are sequenced simultaneously.