{"id":3614,"date":"2016-09-29T15:06:13","date_gmt":"2016-09-29T13:06:13","guid":{"rendered":"https:\/\/www.toulouse-white-biotechnology.com\/insights\/actualites\/actualite\/synthetic-genomes-and-the-myth-of-perfection\/"},"modified":"2026-03-16T13:52:45","modified_gmt":"2026-03-16T12:52:45","slug":"synthetic-genomes-and-the-myth-of-perfection","status":"publish","type":"post","link":"https:\/\/www.toulouse-white-biotechnology.com\/en\/insights\/blog\/news\/synthetic-genomes-and-the-myth-of-perfection\/","title":{"rendered":"Synthetic genomes\u00a0and the myth of perfection"},"content":{"rendered":"Designing a synthetic genome: for whom, what for? What are the concepts behind this first step towards the creation of artificial living species?\u00a0<\/strong>\n\n

The genome (genetic material) of an organism constitutes a major element of the transmissible information enabling the<\/p>\n\n perpetuation of a species<\/strong>\n\n

and of its individuals. Since the synthesis in 2008 of the first complete synthetic genome, that of<\/p>\n\nMycoplasma mycoides<\/em>\n\n

,<\/p>\n\nmany projects have been started, targeting the total synthesis of artificial genomes of bacteria or eukaryotic species such as yeast<\/strong>\n\n

. However, de novo synthetizing a genome is only a first step towards the creation of synthetic living organisms, in the sense that it is still impossible to reconstruct a living being without having, in addition to the genetic information, a natural cellular host structure able to accept it and provide a suitable expression environment. It is nevertheless a<\/p>\n\nmajor life reprogramming tool<\/strong>\n\n

which, even if there is still a long way to go, could be extended to a very wide range of species including not only microorganisms, but also plants, animals, and ultimately man. Concerning the latter, it is no longer altogether science-fiction, as evidenced by the emergence, recently mediatized at Harvard in the USA, of a consortium of scientists seriously considering the possibility of the complete synthesis of a human genome.<\/p>\n\nWhat is the rationale underlying the creation of artificial genomes?<\/strong>\n\n

In what way is it more than a simple extrapolation, to different scales, of natural genome engineering as practiced for years by biotechnologies? Beyond the technical approaches implemented, some of which can be innovative, the major difference lies in the purposes.<\/p>\n\nClassic genetic engineering targets the acquisition, the loss, or the correction of specific functions<\/strong>\n\n

in an organism of industrial interest or with a therapeutic objective, for example in the case of gene therapy. In contrast, and beyond the challenge and what it can bring in terms of knowledge of life\u2019s \u201clogic\u201d,<\/p>\n\ndesigning a synthetic genome<\/strong>\n\n

is more often governed by an \u201cidealization\u201d\u00a0rationale aiming at recreating an organism if possible<\/p>\n\nfree of \u201cdefects\u201d<\/strong>\n\n

. It should then serve as an<\/p>\n\noptimal springboard for the implementation of a wide range of non-natural functions<\/strong>\n\n

. In other terms, creating an organism in the image of our current or future needs and not of those having ruled over natural evolution.<\/p>\n\n

\"splice\"<\/figure>\n\n

Credits: image of the film Splice produced by Vincenzo Natali \u2013 source Internet<\/em><\/p>\n\n

At this stage, it should be recalled that the size of a genome is very variable (factor from 1 to 10 000) and is not only related to the physical or functional complexity of the organism. The genes that encode proteins and which are the easiest functional blocks to define represent only a small fraction of the information present. Their number varies relatively little from one organism to another (factor of 5 between E. coli and man). The large genomes contain therefore a majority of so-called non-coding DNA whose long-neglected role is in fact multiple: it intervenes in particular through micro-RNAs in many regulation mechanisms, often still poorly characterized, but critical for the organism. More generally,<\/p>\n\nthe number and the nature of genes but also their structuring within the genomes play a determining informational role.<\/strong>\n\n

The notion of<\/p>\n\nminimal genome<\/strong>\n\n

is often associated with that of synthetic genome. The rationale seems simple: to keep only the essential, since genome size is extremely variable even for organisms with similar functions. In fact, the definition of this minimum is complex. Whereas defining the genes performing the basic<\/p>\n\nmaintenance tasks<\/strong>\n\n

of an organism is relatively easy, the myriad of other information encoding the<\/p>\n\ncomplex regulation networks<\/strong>\n\n

and the auxiliary genes or duplications is another matter. These mechanisms are critical for an organism\u2019s<\/p>\n\nrobustness or adaptive capacities<\/strong>\n\n

and compose critical elements for applications in industrial biotechnology. Neglecting them is in particular one of the main causes of failure during process upscaling.\r\n\r\nThis interaction network defines the function of a genome as a whole and makes it<\/p>\n\nunrealistic to design a synthetic genome as a simple rational sum of functional elements<\/strong>\n\n

. Defining the optimal structure of these networks is now a major objective of synthetic genome design, in particular through the setting up of artificial recombination mechanisms catalyzing the random rearrangement of the functional elements. The associations so created are then compared to the characteristics of the corresponding organism to identify the critical couplings.\r\n\r\nNevertheless, the<\/p>\n\n myth of perfection<\/strong>\n\n

, that of genomes drawn by the hand of man for man, that would surpass in every respect the creations of nature, may seem to be a pipe dream.<\/p>\n\nFunctional richness, robustness, adaptability, performance, and size, require compromises<\/strong>\n\n

, themselves constrained by the DNA coding capacity. The latter may seem mathematically almost infinite but it is in fact strongly limited by the very nature of biological mechanisms. The natural solutions probably owe in part their complexity to adaptation and evolution constraints that\u00a0are generally not necessary or desirable in the context of an industrial process. There is scope for simplification but defining its rules and parameters still remains a challenge.\r\n\r\nThe choice between a<\/p>\n\nde novo<\/em>\n\n

design which claims to be \u201chumanly\u201d rational and the editing, even complex, respecting the solutions retained by nature, remains a difficult choice, especially since the recent development of natural genome editing technologies such as CRISPR-CAS9 greatly facilitates the second approach.<\/p>\n\nTo create\u00a0may seem to be more noble than to correct, but nature had millions of years to test solutions and their consequences, will we be able to do better and what for?<\/strong>\n\n

More information:<\/h2>\n\n