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. 2002 Dec 10;99(25):16144-9.
doi: 10.1073/pnas.242624799. Epub 2002 Nov 21.

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Maitreya J Dunham  1 , Hassan Badrane, Tracy Ferea, Julian Adams, Patrick O Brown, Frank Rosenzweig, David Botstein
Affiliations

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae

Maitreya J Dunham et al. Proc Natl Acad Sci U S A. .

Abstract

Genome rearrangements, especially amplifications and deletions, have regularly been observed as responses to sustained application of the same strong selective pressure in microbial populations growing in continuous culture. We studied eight strains of budding yeast (Saccharomyces cerevisiae) isolated after 100-500 generations of growth in glucose-limited chemostats. Changes in DNA copy number were assessed at single-gene resolution by using DNA microarray-based comparative genomic hybridization. Six of these evolved strains were aneuploid as the result of gross chromosomal rearrangements. Most of the aneuploid regions were the result of translocations, including three instances of a shared breakpoint on chromosome 14 immediately adjacent to CIT1, which encodes the citrate synthase that performs a key regulated step in the tricarboxylic acid cycle. Three strains had amplifications in a region of chromosome 4 that includes the high-affinity hexose transporters; one of these also had the aforementioned chromosome 14 break. Three strains had extensive overlapping deletions of the right arm of chromosome 15. Further analysis showed that each of these genome rearrangements was bounded by transposon-related sequences at the breakpoints. The observation of repeated, independent, but nevertheless very similar, chromosomal rearrangements in response to persistent selection of growing cells parallels the genome rearrangements that characteristically accompany tumor progression.

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Figures

Fig 1.
Fig 1.
Pulsed-field gel electrophorogram of the intact chromosomes from each yeast strain. M, yeast chromosome markers. Marker bands are labeled by chromosome. E1–E8, evolved strains; C, CP1AB.
Fig 2.
Fig 2.
Genomewide copy number in the evolved strains. Genes are plotted by coordinate along each chromosome. Copy numbers were obtained by multiplying the average of two evolved strain/CP1AB copy number ratios by 2, because CP1AB is a WT diploid. The confirmed amplification of HXT6 in E1 is highlighted in purple. A measurement was colored red or green if the running average of nine genes centered at the query gene was beyond 99.9% of the data in the control experiment. Small black circles along each plot represent the centromeres. Copy number scale ranges from 0 to 6.
Fig 3.
Fig 3.
Inferred karyotype of E4. Only chromosomes 7 and 15 are shown; all other chromosomes are diploid. In E4 the dashed section of chromosome 7 has become triploid by translocating to chromosome 15, causing a deletion of one copy of the dashed section of 15. The number of centromeres remains 32. The full-length chromosome 15 and the translocation would segregate 2:2 in tetrads.
Fig 4.
Fig 4.
Log2 transformed ratios from DNA microarrays of PFGE band DNA compared with a constant reference of CP1AB plug DNA. Log2 ratios for each gene are plotted in chromosome order; the vertical scales are different for each comparison (see http://genome-www.stanford.edu/rearrangements/ for details). Only chromosomes with enriched regions are shown. The section of each chromosome enriched in the excised band is colored red, with the rest of the chromosome colored gray. The boundary defining these classifications was determined by finding the minimum between the two peaks of the bimodal histogram of a running average of three genes along each chromosome.
Fig 5.
Fig 5.
E4 and E7 rearrangements. The breakpoints of the rearrangements described in Table 3 are schematized by using map information from the Saccharomyces Genome Database. Red and gray coloring is as in Fig. 4. Light purple arrows are Ty terminal repeats. Blue arrows are tRNA genes. The depicted crossover regions were determined by sequencing as described in the text.
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