细菌最小基因组研究进展

doi:10.16288/j.yczz.20-301

遗传 ›› 2021, Vol. 43 ›› Issue (2): 142-159.doi: 10.16288/j.yczz.20-301

细菌最小基因组研究进展

李金玉^1,^2,³(), 杨姗^2,³, 崔玉军^2,³, 王涛¹, 滕越^2,³()

¹ 天津大学生命科学学院,天津 300110
² 军事科学院军事医学研究院微生物流行病研究所,北京 100071
³ 病原微生物生物安全国家重点实验室,北京 100071

收稿日期:2020-11-23 出版日期:2021-02-16 发布日期:2021-01-27
基金资助:
国家科技重大专项(2018ZX10101003-002-011);“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项(2018ZX10712-001-003)

Research progress of bacterial minimal genome

Jinyu Li^1,^2,³(), Shan Yang^2,³, Yujun Cui^2,³, Tao Wang¹, Yue Teng^2,³()

¹ School of Life Sciences, Tianjin University, Tianjin 300110, China
² Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China
³ State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China

Received:2020-11-23 Online:2021-02-16 Published:2021-01-27
Supported by:
the National Science and Technology Major Project(2018ZX10101003-002-011);the Major Infectious Diseases Such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects(2018ZX10712-001-003)

摘要/Abstract

摘要：

具有最小基因组的细菌只包含维持自我生命复制所必需的基因,其作为一种潜在的工业生产平台具有诸多优势。由于高通量DNA测序和合成技术的发展,目前已经构建了多种缩减基因组的菌株。本文首先介绍了最小基因组的概念,其次总结了细菌必需基因的相关研究进展,然后梳理了人工缩减与合成微生物基因组的相关工作,最后探讨了在设计和组装基因组的过程中遇到的技术障碍和限制,以期为人工合成基因组的实验与应用提供理论参考。

关键词: 细菌, 最小基因组, 必需基因, 合成生物学, 人工设计

Abstract:

Bacteria with the smallest genome contain genes necessary for self-sustaining replication only, giving the organisms advantages to serve as a potential industrial production platform. Many strains with reduced genomes have been constructed, owing to the development of high-throughput DNA sequencing and synthesis technology. This review first describes the concept of minimal genomes, summarizes the relevant research progress of bacterial essential genes, then systematically lists the work related to artificial reduction and synthesis of bacterial genomes, finally discusses the technical obstacles and limitations encountered in the process of designing and constructing reduced genomes, hoping to provide a theoretical basis for the experiment and application of artificially synthesized genomes.

Key words: bacteria, minimal genome, essential genes, synthetic biology, artificial design

李金玉, 杨姗, 崔玉军, 王涛, 滕越. 细菌最小基因组研究进展[J]. 遗传, 2021, 43(2): 142-159.

Jinyu Li, Shan Yang, Yujun Cui, Tao Wang, Yue Teng. Research progress of bacterial minimal genome[J]. Hereditas(Beijing), 2021, 43(2): 142-159.

图/表 5

图1

表1

具有代表性的细菌、共生生物、病毒和细胞器基因组的比较"

微生物	分类^a	基因组大小(bp)	GC含量(%)	蛋白质编码序列数	位于COGs M簇和I簇的基因数目^b	细胞形态	杆状决定基因
微生物	分类^a	基因组大小(bp)	GC含量(%)	蛋白质编码序列数	位于COGs M簇和I簇的基因数目^b	细胞形态	ftsZ	ispA	mreB	rodA
	游离细菌
Escherichia coli	γ-变形菌纲	4,639,675	50.8	4145	323	杆状^[46]	+	+	+	+
Bacillus subtilis	柔膜菌纲	4,215,606	43.5	4176	307	杆状^[46]	+	+	+	+
Rickettsia prowazekii	α-变形菌纲	1,111,523	29.0	835	100	杆状^[47]	+	-	+	+
Mycobacterium genitalium	Mollicutes	580,076	31.7	475	17	'烧瓶形' ^[48]	+	-	-	-
	缩减基因组共生生物
Candidatus Blochmannia floridanus	γ-变形菌纲	705,557	27.4	583	77	杆状^[49]	+	-	+	+
Wigglesworthia glossinidia	γ-变形菌纲	697,724	22.5	611	85	杆状^[50]	+	+	+	+
Candidatus Baumannia cicadellinicola	γ-变形菌纲	686,194	33.2	595	62	球状^[51]	+	+	+	+
Buchnera aphidicola str. APS	γ-变形菌纲	640,681	26.3	564	41	球状^[52]	+	+	-	-
Candidatus Moranella endobia'	γ-变形菌纲	538,294	43.5	406	36	球状^[53]	+	-	+	+
Buchnera aphidicola str. Cc	γ-变形菌纲	416,380	20.2	357	10	球状^[54]	+	-	-	-
	极端缩减基因组共生生物
Candidatus Sulcia muelleri str. GWSS	黄杆菌纲	245,530	22.4	227	5	多形性管状^[55]	-	-	-	-
Candidatus Zinderia insecticola	β-变形菌纲	208,564	13.5	202	1	多形性斑点^[56]	-	-	-	-
Candidatus Carsonella ruddii	γ-变形菌纲	159,662	16.6	182	1	多形性管状^[57]	-	-	-	-
Candidatus Hodgkinia cicadicola	α-变形菌纲	143,795	58.4	169	0	多形性管状^[58]	-	-	-	-
Candidatus Tremblaya princeps	β-变形菌纲	138,927	58.8	121	0	多形性斑点^[53]	-	-	-	-
	具有较大基因组的细胞器
Cucurbita pepo	线粒体	982,833	42.8	38	NA	NA	-	-	-	-
Floydiella terrestris	叶绿体	521,168	34.5	74	NA	NA	-	-	-	-
Porphyra purpurea	叶绿体	191,028	33.0	209	NA	NA	-	-	-	-
Reclinomonas americana	线粒体	69,034	26.1	67	NA	NA	-	-	-	-
	巨大病毒
Acanthamoeba polyphaga mimivirus	拟菌病毒科	1,181,404	28.0	1262	NA	NA	NA	NA	NA	NA
Cafeteria roenbergensis virus (CroV)	拟菌病毒科	617,453	23.4	544	NA	NA	NA	NA	NA	NA
Coccolithovirus	藻类DNA 病毒科	407,339	40.2	472	NA	NA	NA	NA	NA	NA

表1

图2

表2

图3

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原始菌株	缩减基因组菌株名称	原始基因组大小(Mb)	缩减量(%)	特征
Escherichia coli str. K-12 substr. MG1655	CDΔ3456	4.64	313 kb (6.8)	生长速度正常
Escherichia coli str. K-12 substr. MG1655	MDS12	4.64	376 kb (8.1)	生长速度正常,细菌生长密度提高10%
Escherichia coli str. K-12 substr. MG1655	MDS42	4.64	708 kb (15.3)	生长速度正常,更高的转化效率
Escherichia coli str. K-12 substr. MG1655	MS56	4.64	1068 kb (23.0)	生长速度正常,遗传稳定性提高
Escherichia coli str. K-12 substr. MG1655	Δ16	4.64	1377 kb (29.7)	较低的生长速度,异常的拟核结构
Escherichia coli str. K-12 substr. W3110	MGF-01	4.65	1030 kb (22.2)	细菌生长密度提高50%,更高的苏氨酸产量
Bacillus subtilis str. 168	Δ6	4.22	320 kb (7.7)	生长速度正常
Bacillus subtilis str. 168	PG10	4.22	1456 kb (34.5)	较低的生长速度
Bacillus subtilis str. 168	PG38	4.22	1535 kb (36.4)	较低的生长速度
Bacillus subtilis str. 168	MGB469	4.22	469 kb (11.1)	生长速度正常
Bacillus subtilis str. 168	MG1M	4.22	991 kb (23.5)	生长速度正常
Bacillus subtilis str. 168	MBG874	4.22	874 kb (20.7)	较低的生长速度,更高的蛋白产量
Streptomyces avermitilis	SUKA17	9.03	1674 kb (18.5)	更高的抗生素产量
Schizosaccharomyces pombe	A8	12.6	657 kb (5.2)	更高的蛋白产量

细菌最小基因组研究进展

Research progress of bacterial minimal genome

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