Abstract #78

Amplification of Histone Genes in Saccharomyces cerevisiae. Diana E. Libuda, Fred Winston. Department of Genetics, Harvard Medical School, Boston, MA.
   Gene amplification, a process that increases the copy number of a gene or genomic region to two or more, is utilized by many organisms during development, in response to environmental stress, or in response to decreased levels of a gene product. Our studies have identified a previously unknown amplification of a histone locus. In Saccharomyces cerevisiae, histones H2A and H2B are encoded by two gene pairs, named HTA1-HTB1 and HTA2-HTB2. Previous studies have shown that an (hta1-htb1)D mutation causes transcriptional defects, while an (hta2-htb2)D mutation causes no detectable defects, due to the ability of HTA1-HTB1 to dosage compensate at the transcriptional level. Based on the observation that the mutant phenotypes of (hta1-htb1)D strains are unstable, we tested the stability of the HTA2-HTB2 locus. We have found that in response to deletion of HTA1-HTB1, HTA2-HTB2 becomes amplified by the creation of a new circular chromosome, containing an approximately 40 kilobase region of chromosome II that includes HTA2-HTB2, origins of replication, and the centromere. Our results strongly suggest that this 40 kb circular chromosome is formed by recombination between two flanking Ty1 elements. Furthermore, we have found that each of these flanking Ty1 elements is required for the amplification. Additional experiments have shown that formation of the 40 kb chromosome is required for the viability of (hta1-htb1)D strains and occurs at a frequency significantly greater than that observed for most gene duplications or Ty-Ty recombination events. These results demonstrate another mechanism by which histone gene dosage may be altered and for genomes to adapt to allow changes in gene activity.

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