Methods and compositions for generating asymmetrically-tagged nucleic acid fragments

A method of nucleic acid sequencing, comprising:

• providing a nucleic acid construct that comprises a double-stranded central region, two hairpin end regions, and one or more single-stranded nicks or single-stranded gaps;
• contacting the nucleic acid construct to a polymerase under nucleic acid synthesis conditions, wherein the polymerase initiates template-dependent nucleic acid synthesis from the one or more nicks or gaps in the construct to produce a nucleic acid synthesis product, which nucleic acid synthesis product comprises a double-stranded region, one of the two hairpin end regions, and an end opposite this one hairpin end region;
• ligating an adapter to the nucleic acid synthesis product, wherein the adapter is ligated to the end opposite the hairpin end region on the nucleic acid synthesis product, and wherein the adapter has at least one difference as compared to the hairpin end region on the nucleic acid synthesis product, thereby producing an asymmetrically-tagged nucleic acid;
• and
• then determining a nucleotide sequence of at least one strand of the double-stranded region of the asymmetrically-tagged nucleic acid.