Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus

David Gresham, Renata Usaite, Susanne Manuela Germann, Michael Lisby, David Botstein, Birgitte Regenberg

Research output: Contribution to journalArticlepeer-review


To study adaptive evolution in defined environments, we performed evolution experiments with Saccharomyces cerevisiae (yeast) in nitrogen-limited chemostat cultures. We used DNA microarrays to identify copy-number variation associated with adaptation and observed frequent amplifications and deletions at the GAP1 locus. GAP1 encodes the general amino acid permease, which transports amino acids across the plasma membrane. We identified a self-propagating extrachromosomal circular DNA molecule that results from intrachromosomal recombination between long terminal repeats (LTRs) flanking GAP1. Extrachromosomal DNA circles (GAP1circle) contain GAP1, the replication origin ARS1116, and a single hybrid LTR derived from recombination between the two flanking LTRs. Formation of the GAP1circle is associated with deletion of chromosomal GAP1 (gap1Δ) and production of a single hybrid LTR at the GAP1 chromosomal locus. The GAP1circle is selected following prolonged culturing in L-glutamine-limited chemostats in a manner analogous to the selection of oncogenes present on double minutes in human cancers. Clones carrying only the gap1Δ allele were selected under various non-amino acid nitrogen limitations including ammonium, urea, and allantoin limitation. Previous studies have shown that the rate of intrachromosomal recombination between tandem repeats is stimulated by transcription of the intervening sequence. The high level of GAP1 expression in nitrogen-limited chemostats suggests that the frequency of GAP1circle and gap1Δ generation may be increased under nitrogen-limiting conditions. We propose that this genomic architecture facilitates evolvability of S. cerevisiae populations exposed to variation in levels and sources of environmental nitrogen.

Original languageEnglish (US)
Pages (from-to)18551-18556
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - Oct 26 2010


  • Adaptive evolution
  • Double minute
  • Genome plasticity
  • Intrachromosomal recombination
  • Retrotransposon

ASJC Scopus subject areas

  • General


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