英国《自然》杂志网站9月14日登载的一份研究报告说，美国研究人员首次人工合成一种真核生物——酵母的部分基因组，目前含这种人工基因组的酵母正常存活。
美国约翰斯·霍普金斯大学医学院等机构的研究人员报告说，他们对酵母的两个染色体片段进行改造，删去了其中重复的部分基因序列，尔后添加一些人工合成的基因序列，经人工改造的基因序列约占整个酵母基因组的1%。酵母在接纳如此“加工”的基因组后，仍能正常存活，未出现明显异常。
此前曾有研究人员人工合成过一种细菌的基因组，但细菌属于原核生物，而酵母属于更高级的真核生物。本次研究是世界上首次成功合成真核生物的部分基因组，标志人工合成生物基因组的研究又迈出了重要步伐。
本次研究的一个亮点是研究者在人工基因组中设计了一种“混杂”系统，这种系统可通过激活相应的酶来开启，系统开启后可以删除某些基因或重新安排基因序列，酵母亦随之发生相应的变异。通过这种方式能够得到不同属性的酵母，比如生长率、对药物敏感程度、温度敏感性都不同的酵母，可用于不同目的的研究。
领导这项研究的杰夫·伯克说，“混杂”系统可成为深入研究基因的手段，比如用来探索基因组被删去多少后生物仍能存活，或是探索基因组被打乱、改变到什么程度才会产生新物种。（生物谷 Bioon.com）
doi:10.1038/nature10403
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BoekeSynthetic chromosome arms function in yeast and generate phenotypic diversity by design
Jessica S. Dymond; Sarah M. Richardson; Candice E. Coombes; Timothy Babatz; Héloïse Muller; Narayana Annaluru; William J. Blake; Joy W. Schwerzmann; Junbiao Dai; Derek L. Lindstrom; Annabel C. Boeke; Daniel E. Gottschling; Srinivasan Chandrasegaran; Joel S. Bader; Jef D. Boeke
Recent advances in DNA synthesis technology have enabled the construction of novel genetic pathways and genomic elements, furthering our understanding of system-level phenomena1, 2, 3, 4, 5, 6, 7. The ability to synthesize large segments of DNA allows the engineering of pathways and genomes according to arbitrary sets of design principles. Here we describe a synthetic yeast genome project, Sc2.0, and the first partially synthetic eukaryotic chromosomes, Saccharomyces cerevisiae chromosome synIXR, and semi-synVIL. We defined three design principles for a synthetic genome as follows: first, it should result in a (near) wild-type phenotype and fitness; second, it should lack destabilizing elements such as tRNA genes or transposons8, 9; and third, it should have genetic flexibility to facilitate future studies. The synthetic genome features several systemic modifications complying with the design principles, including an inducible evolution system, SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution). We show the utility of SCRaMbLE as a novel method of combinatorial mutagenesis, capable of generating complex genotypes and a broad variety of phenotypes. When complete, the fully synthetic genome will allow massive restructuring of the yeast genome, and may open the door to a new type of combinatorial genetics based entirely on variations in gene content and copy number.
