Werner Arber | PAS President Emeritus for Life

Horizontal gene transfer in the context of a rich biodiversity

Astrophysical research indicates that the Milky Way with our Solar System must have an age of about 4,000 million years. Life on our planet Earth must have started with primitive microorganisms about 3,500 million years ago, but it remains unknown how they originated. In the course of time stepwise evolution then gave rise to a multitude of different microorganisms and then also of various multicellular living organisms including plants and animals. This stepwise evolutionary progress resulted in today’s high biodiversity on our planet Earth by a remarkable process of permanent creation. I will report here on results and implications that have recently become revealed by intensive research. Bacteria have served as excellent testing ground to uncover mechanisms of evolution because of their fast replication times, as I will now illustrate with some examples.

In general, biological activities are guided by genetic information carried in the genome. In E. coli bacteria the genome is generally a circular double-stranded DNA molecule. Its genetic information resides in the specific sequences of the 4 nucleotides adenine, thymine, guanine and cytosine. In comparison with our written language, the size of the bacterial genome corresponds to the size of a book. Some bacteria also carry so-called plasmids, small DNA molecules of the size of one page. This is, in general, also the size of bacterial viruses, which we call phages.

Single steps of microbial evolution require usually appropriate genetic variations in the genome. A number of specific mutational mechanisms can fulfil this request. So far, the studied mechanisms of genetic variation can be grouped into 3 strategies:

(1) Point mutants with an alteration of one or a few adjacent nucleotides can result upon DNA replication at a site of a short-living tautomeric nucleotide. Tautomeric adenine pairs upon DNA replication with cytosine instead of thymine, and tautomeric guanine pairs with thymine instead of cytosine. A point mutation thereby results if this kind of replication error escapes a repair process shortly after its production.

(2) Genomes are known to carry at various sites so-called mobile genetic elements. Occasionally such an element can excise from its location and then integrate at another site in the genome. This process is called transposition and it can sometimes produce a new functional fusion acting as genetic variant.

(3) The third strategy to equip a bacterial cell with a novel genetic capacity is the horizontal (also called lateral) gene transfer. This process can involve conjugation, transduction or transformation. The thereby taken-up foreign DNA segments can be properly read by the recipient cell thanks to the universal genetic code.

Some intestinal bacteria carry a fertility plasmid F. Its function is to build a pair with another kind of bacterium in a mixed population and then transfer a segment of its donor DNA into its partner cell. Parts of this transferred DNA can then sometimes become integrated into the genome of the recipient cell. This process it called conjugation.

Upon transduction a bacterial virus such us phage P 1 having been replicated in a donor bacterium and carrying some genes of the donor bacterium can infect a recipient cell that may then integrate a segment of the donor DNA into its genome. If the phage renders the infected cell lysogenic the cell survives and the transduced genes from the donor cell can become expressed. The acquired DNA can sometimes represent a welcome new function for the recipient bacterium.

Some bacteria such as Streptococcus are able to take up DNA molecules liberated by other genetically related bacterial strains. This kind of horizontal gene transfer is called transformation.

Many bacterial strains are genetically equipped with a restriction/modification system. They can verify the origin of taken-up DNA molecules. Their own DNA is marked by methylation at each strain-specific sequence of a few nucleotides. This is done by the modification enzyme. The restriction enzyme can identify on the taken-up DNA the same nucleotide sequences that are not methylated. These non-methylated nucleotides then give rise to cut the taken-up DNA into fragments which are then acid solubilized by the cellular exonuclease, unless they have been protected from destruction by a fast integration into the genome of the recipient cell.

The intestinal E. coli bacteria serving for these experiments are propagated in the laboratory in appropriate growth medium at 37 degrees Celsius. Their generation time is then about 30 minutes. During their intensive growth they can occasionally produce a point mutant at any base-pair. Also, occasionally, one of the mobile genetic elements can transpose to another site in the genome. If the bacterial cells propagate in a mixture with other bacterial strains, as it is usually the case upon growth in a microbiome, it occasionally can happen that events of horizontal gene transfer occur by conjugation or by transduction. The 3 strategies of forming various genetic variants are relatively rare. Some of the produced mutants may enable their cells to also grow in an alternative growth medium in which the original bacteria are unable to propagate.

The processes of genetic adaptation described here occur in the involved bacteria by what we call self-organization. By self-organization we mean that the genome has the ability to reorganize by itself, but it does so at a rather low frequency in order to maintain most cells genetically stable, thereby not taking risks that would be too big for evolutionary progress. Another relevant conclusion is the fact that creation is a permanent process in view of the steady evolution of the living organisms in their also evolving living conditions. I am convinced that these conclusions are generally valid for living organisms.

Horizontal gene-transfer is not limited to micro-organisms. It can also occur by eukaryotic organisms as shown by systematic nucleotide sequence analysis.

Our human civilization still profits from the presence of a relatively rich biodiversity enabling occasional horizontal gene transfer to other kinds of organisms. But today’s worldwide life-conditions implicate a steady loss of genetic information. A major reason for this bad situation resides in the increasing transformation of wildtype habitats on our planet by an intensive use of agriculture, human habitations and other purposes. We must be aware that our planet does not grow. Therefore, the human population should reach and then maintain a relatively stable size compatible with planetary limits. We have to be better aware that our human activities should take care of the remarkable richness of the planetary biodiversity. In view of the role played by a steadily occurring horizontal gene transfer in the biological evolution of any kind of living organisms, it is our duty to preserve the worldwide richness of all kinds of specific genes. We have to be aware that a longterm further evolution of life is likely to depend intensively on the available genetic capacities.

Advanced secure methods of genetic engineering can enable us to undertake horizontal gene transfer for relevant use. Examples are the production of Golden Rice and of bacteria able to produce spider silk.

In conclusion, the appreciated rich diversity of living organisms on our planet not only goes back to a common origin, but it can also profit from a common future by occasional horizontal gene transfer.