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我是谁?——Holobionts and Hologenomes

不要小看这个问题,“我(I)”或将成为一个废词,微生物菌们已经不服气人类自我统治了那么久了。在我们走来走去工作、睡觉的时候,肚子里还藏着一个庞大的生态系统——微生物菌群。

我们自从出生的那天起,身体就是一个细菌的乐园。一个成人体内的细菌总重量大约有1.5公斤,一般认为其总数至少是人体总细胞数的10倍。 随着高通量技术的发展,生物数据面临大爆发式地增长。科学家们估计人体细菌种类多达500-1000种,这些细菌的基因总数与人体相当,而基因总数则可能是人体的100倍以上。

人体内有两个基因组,一个是从父母那里遗传来的人基因组,编码大约2.5万个基因;另一个则是出生以后才进入人体、特别是肠道内的多达1000多种的共生微生物,其遗传信息的总和叫“微生物组”,也可称为“元基因组”,它们所编码的基因有100万个以上。两个基因组相互协调、和谐一致,保证了人体的健康。因此,在研究基因与人体健康关系时,一定不能忽略共生微生物基因的研究。 研究显示:我们常常将自己认为是生物分子网络的一员,这样的话实在是太无视我们自身的微生物了。实际上,我们体内成千上万的细菌才是我们身体健康的主角。它决定了我们身体的成长,对疾病的抵御,甚至是可以控制人类的一些行为。 Vanderbilt大学的生物科学副教授Seth Bordenstein在研究共生微生物方面具有卓越的成就,他表示,对微生物组学的研究效果远大于对各个部分研究的效果之和。 在微生物组学项目中,成千上万的基因组组成了微生物信息。微生物学家已经为这些实体重新命名,对实体命名为“holobiont”,他们的基因组为“hologenome”,这些这些实体才能组成了我们个人。Seth Bordenstein和同事将上述观点发表在8月18日PLOS子刊上文章。

这或许是基于自然选择的进化论结果,微生物的突变不仅影响机体的健康,同样对其他基因组突变的作用至关重要。holobionts针对环境有一个专门的应对机制:它们具有改变细菌菌群的作用。例如,如果一个holobionts被病原体所供给,并且机体无法抵御它。那么其他的共生生物可能会释放杀伤性的毒素来抵御病原体。在这方面,微生物是holobionts的免疫系统,随着基因突变,使得免疫功能提高。 根据Bordenstein的讲解,越来越多的人接受微生物菌群这个观点。

在6月份召开的美国微生物学会(American Society of Microbiology General Meeting),Bordenstein主持了一个叫做'Holobionts and Their Hologenomes'学术研讨会,他表示明年将发布一些有关“微生物菌群”更加新颖的观点。然而也有科学家表示,尽管上述的观点很有用,但是其在实践中的应用要慢得多。 Bordenstein表示:尽管现在人们在微生物学、动物学和植物学等领域的研究有所突破,但是并没有互相交融,因此进行微生物环境基因组学、元基因组学的研究不仅会影响到生物基础学科的研究,还将对个体化医药的作用巨大。 尽管全基因组测序在解决遗传信息丢失方面进展颇多,然而一旦涉及到一些复杂的疾病(自身免疫和代谢疾病)的研究,必须要拓展到微生物组学领域,这将解决传统遗传信息出现丢失的问题。

不要忘了,我们需要接受这样一个事实,我们生命受益于微生物世界:外部,我们受益于环境微生物;内部,我们受益于肠道微生物菌群。 随着科技的发展,通过绘制人体不同器官中微生物元基因组图谱,解析微生物菌群结构变化对人类健康的影响至关重要。一旦这些秘密被破解,“我”也不再是简单的存在,而是与许许多多的微生物共生在一起。

The Ten Principles of Holobionts and Their Hologenomes

I. Holobionts and hologenomes are units of biological organization Complex multicellular eukaryotes are not and have never been autonomous organisms, but rather are biological units organized from numerous microbial symbionts and their genomes. Biomolecular associations between host and microbiota are more conceptually similar to an intergenomic, genotype x genotype interaction than a genotype x environment interaction.

II. Holobionts and hologenomes are not organ systems, superorganisms, or metagenomes As holobionts are complex assemblages of organisms consisting of diverse microbial genomes, biology should draw a clear distinction between holobionts/hologenomes and other terms that were not intended to describe host–symbiont associations. Organ systems and superorganisms are biological entities comprised of one organism's genome; metagenome means 'after' or 'beyond' the genome, does not intrinsically imply organismality, and obviates the fundamentals of symbiosis in the holobiont.

III. The hologenome is a comprehensive gene system The hologenome consists of the nuclear genome, organelles, and microbiome. Beneficial, deleterious, and neutral mutations in any of these genomic subunits underlie hologenomic variation.

IV. The hologenome concept reboots elements of Lamarckian evolution Although Lamarck never imagined microbes in his theory, applying the tenets to holobionts rebirths some major aspects of Lamarckism. The nuclear genome is inherited mainly within a Mendelian framework, but the microbiome is originally acquired from the environment and may become inherited. Host–microbe associations can forge disequilibria via parental transfer or stable environmental transmission.

V. Hologenomic variation integrates all mechanisms of mutation Every hologenome is a multiple mutant, meaning that there is variation across many individual genomes spanning the nucleus, organelles, and microbiome. Base pair mutation, horizontal gene transfer, recombination, gene loss and duplication, and microbial loss and amplification are all sources of variation.

VI. Hologenomic evolution is most easily understood by equating a gene in the nuclear genome to a microbe in the microbiome Evolution for both genes and symbionts is fundamentally a change in population frequency over successive generations, i.e., the fraction of holobionts carrying that particular nuclear allele or microbe. Covariance of hosts and microbes in a holobiont population (i.e., community genetics) follows a theoretical continuum directly to coinheritance of gene combinations within a genome (i.e., population genetics). A grand unified theory of evolutionary and ecological genetics deserves priority attention.

VII. The hologenome concept fits squarely into genetics and accommodates multilevel selection theory Multilevel selection theory asserts that selection operates across multiple levels of genetic variation with phenotypic effects, from genes to hologenomes and beyond. Holobionts are exclusive to hosts and their associated microbiota; different holobionts, such as a pollinator and a flower, interact with each other under standard ecological principles.

VIII. The hologenome is shaped by selection and neutrality Natural selection can work to remove deleterious nuclear mutations or microbes while spreading advantageous nuclear mutations or microbes; in the absence of selection, the neutral spread of hologenomic variation through populations is an inherently stochastic process. Mixed ecological models of stochastic and deterministic community assembly likely reflect natural systems, and partitioning the microbiota into stochastic versus deterministic subunits will be an important future goal of the field.

IX. Hologenomic speciation blends genetics and symbiosis The Biological Species Concept was never intended to be exclusive of symbiosis, though history largely divorced the two and created unnecessary controversy. Antibiotic or axenic experiments in speciation studies must be a routine, if not obligatory, set of experiments in genetic analyses of speciation for an all-inclusive understanding of the origin of species.

X. Holobionts and their hologenomes do not change the rules of evolutionary biology Although the concepts redefine that which constitutes an individual animal or plant, they are not a fundamental rewriting of Darwin's and Wallace's theory of evolutionary biology. Simply put, if the microbiome is a major, if not dominant, component of the DNA of a holobiont, then microbiome variation can quite naturally lead to new adaptations and speciation, just like variation in nuclear genes.

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