英國《自然》雜志網(wǎng)站9月14日登載的一份研究報(bào)告說,，美國研究人員首次人工合成一種真核生物——酵母的部分基因組,，目前含這種人工基因組的酵母正常存活。
美國約翰斯·霍普金斯大學(xué)醫(yī)學(xué)院等機(jī)構(gòu)的研究人員報(bào)告說,，他們對(duì)酵母的兩個(gè)染色體片段進(jìn)行改造,，刪去了其中重復(fù)的部分基因序列,，爾后添加一些人工合成的基因序列,，經(jīng)人工改造的基因序列約占整個(gè)酵母基因組的1%。酵母在接納如此“加工”的基因組后，仍能正常存活,，未出現(xiàn)明顯異常,。
此前曾有研究人員人工合成過一種細(xì)菌的基因組，但細(xì)菌屬于原核生物,，而酵母屬于更高級(jí)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組，標(biāo)志人工合成生物基因組的研究又邁出了重要步伐,。
本次研究的一個(gè)亮點(diǎn)是研究者在人工基因組中設(shè)計(jì)了一種“混雜”系統(tǒng),，這種系統(tǒng)可通過激活相應(yīng)的酶來開啟，系統(tǒng)開啟后可以刪除某些基因或重新安排基因序列,，酵母亦隨之發(fā)生相應(yīng)的變異,。通過這種方式能夠得到不同屬性的酵母，比如生長率,、對(duì)藥物敏感程度,、溫度敏感性都不同的酵母，可用于不同目的的研究,。
領(lǐng)導(dǎo)這項(xiàng)研究的杰夫·伯克說，“混雜”系統(tǒng)可成為深入研究基因的手段,，比如用來探索基因組被刪去多少后生物仍能存活,，或是探索基因組被打亂、改變到什么程度才會(huì)產(chǎn)生新物種,。（生物谷 Bioon.com）
doi:10.1038/nature10403
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PMID:
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.
