Center for Genomics and Systems Biology and Department of Biology, New York University, New York, NY 10003, USA.
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18551-6. doi: 10.1073/pnas.1014023107. Epub 2010 Oct 11.
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 (GAP1(circle)) contain GAP1, the replication origin ARS1116, and a single hybrid LTR derived from recombination between the two flanking LTRs. Formation of the GAP1(circle) is associated with deletion of chromosomal GAP1 (gap1Δ) and production of a single hybrid LTR at the GAP1 chromosomal locus. The GAP1(circle) 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 GAP1(circle) 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.
为了在特定环境中研究适应性进化,我们在氮限制的恒化器培养物中进行了酿酒酵母(酵母)的进化实验。我们使用 DNA 微阵列来识别与适应相关的拷贝数变化,并观察到 GAP1 基因座频繁发生扩增和缺失。GAP1 编码通用氨基酸渗透酶,该酶将氨基酸穿过质膜运输。我们鉴定了一种自我传播的染色体外环状 DNA 分子,它是由 GAP1 侧翼的长末端重复序列(LTR)之间的染色体内重组产生的。染色体外 DNA 环(GAP1(circle))包含 GAP1、复制起始点 ARS1116 和一个源自两个侧翼 LTR 之间重组的单个杂交 LTR。GAP1(circle) 的形成与染色体 GAP1(gap1Δ)的缺失和 GAP1 染色体基因座上单个杂交 LTR 的产生有关。在 L-谷氨酰胺限制的恒化器中进行长时间培养后,GAP1(circle) 被选择,这类似于在人类癌症中的双微体上选择致癌基因。在各种非氨基酸氮限制条件下,包括铵、尿素和尿囊素限制,仅携带 gap1Δ 等位基因的克隆被选择。先前的研究表明,串联重复序列之间的染色体内重组率受到中间序列转录的刺激。氮限制恒化器中 GAP1 的高表达水平表明,在氮限制条件下,GAP1(circle) 和 gap1Δ 的产生频率可能会增加。我们提出,这种基因组结构促进了暴露于环境氮水平和来源变化的酿酒酵母种群的可进化性。