Abstract
Genetic carking is a general term for genetic manipulation, leading to alteration of the genetic structure of an individual, or entire population. It was initiated long ago in ancient times as gene therapy with the single purpose of fixing mutations, causing inheritable diseases. However, in the interstellar era, genetic carking reached new popularity, largely exploited by humanity to alter its appearance. By the method of Replication mediated genome reconstruction, it became possible for entirely new humanoid subspecies to evolve, especially in the city of Neverness. The present paper explores the methodology, and possible issues of this technology.
Terminology and technical advance
Genetic carking is a generally accepted term, encompassing a variety of genetic modifications, varying from single gene-single trait to whole genome editing alterations. The origin of the term is disputable. The accepted opinion is that carking is a derivative of cracking, in analogy to software cracking, as genetic carking is a process in which the code of the genome is altered in a desired way, thus allowing it to work differently from what the Creator intended.
The first attempts at genetic carking evolved from genetic therapy and aimed to change, and repair, the DNA sequence of particular genes, leading to a change of a single trait. Such modifications were usually done by using retroviral vectors, introducing a healthy copy of a mutated gene in the recipient. The desired DNA sequence is inserted as an RNA copy into the viral genome, and then, in the infected cells, it is integrated into the host genome by reverse transcription. Initially used as a means of disease curing, later on, it was widely, and illegally, applied as a way to change the appearance in a desired way – hair, or eye color, skin tan, etc. Although well-characterized and still in use, the single gene – single trait approach, as it was lately known has limited application.
The second breakthrough was made with the discovery, or better said, the development of the CRISPR/Cas genome editing technique. Unlike viral vectors, which are mainly good in gene insertion, the CRISPR/Cas technique allowed for genome-wide gene editing. Depending on the guiding RNA, which recognizes a specific DNA sequence in the genome, the Cas family proteins induce cleavage in specific sites, and depending on the design, they may either delete, insert, or both, another DNA sequence by DNA repair mechanisms.
The next step, however, became possible with the enormous power of the Artificial Intelligence. The major problem in front of the genetic engineer is mainly to predict how a particular mutation in the DNA sequence will alter the final trait. By using computing power, he can easily predict the protein structure, that will result from the altered gene, but this is not always a straightforward effect, as altered proteins may have altered interactions, etc. The AI-guided genome editing allowed for a genome-wide prediction of most of the possible effects of any particular gene editing.
All of these techniques were known before the interstellar era, but are still in use, although with limited capacity. However, at this point all available techniques allowed in vivo carking of somatic cells. It was possible for a particular person to alter extensively his appearance, to have blue skin, or no body hair, or cat-like ears, but it was still far from creating an entirely new humanoid species, that can reproduce and give birth to similar individuals.
Replication-mediated genome reconstruction (RMGR)
What if you want to create an entirely new species? Apparently, it won’t be easy to do so from scratch, especially when talking of multicellular eukaryotic organisms. By using genome-wide AI-guided carking, you can alter in the same way one, two, or dozens of individuals, but still, if the reproductive cells are not affected, the resulting individuals may have children, the same as before the carking of their parents.
Therefore, the general idea that was developed was to cark the reproductive cells during their initial formation. It involves specially designed adapter DNA sequences, that attach to specific sequences during the DNA replication in meiosis. Simply said, the adapter DNA serves as a matrix for the newly synthesized polynucleotide chain. The resulting replicated DNA consists of poorly complementary chains, that are recognized by an artificially designed DNA repair system. Unlike the normally existing DNA repair systems, this one recognizes the hypomethylated chain (e.g., the daughter, or newly synthesized chain) as the correct one, degrades the mother chain and completes the replication by adding nucleotides, complementary to the mother chain.
The process is rather sophisticated and involves several major steps:
- Genome design – initially, the RMGR requires a complete redesign of the genome. This AI-mediated task involves the initial input of desired traits. Then extensive search-match-replace prediction identifies the potentially suitable genes from other species, in the entire database, identification of similar genes in the host genome, that must be deleted to avoid duplication of function, followed by simulated gene expression to confirm that the alterations are consistent with a viable organism.
- Synthesis of adapter DNA sequences and construction of the delivery system. It must be said, that the human genome contains nearly 50 000 genes, and depending on the extent of alterations, many of them might need to be edited. Therefore, the number of different adapter DNA may be in the number of thousands, meaning that the delivery system might be quite bulky.
- Introduction to the recipient. Depending on the sex, this might involve simple injection into the testes of the male or additional induction of secondary gametogenesis in females, as the eggs were already formed during the embryonal development.
Finally, the parents are not carked, but their offspring would be, thus giving the origin of a completely new species.
The Alaloi tribes
Although hundreds, if not thousands of different new humanoid species were initiated by RMGR, most of which thrived for centuries, the most well-known were the Alaloi, a synthetic species of cavemen, similar to Neanderthals (Homo neanderthalensis) in their appearance. The accepted scientific name Homo sapiens subsp. pseudoneanderthalensis.
Some estimations showed that the difference between a human and a Neanderthal genome accounts for only 0.5%. However, not all of these differences were crucial for the AI to generate an acceptable humanoid with caveman appearance. The approximate genetic difference between the two subspecies was only 0.3% and interbreeding was possible without any obstacles.
The Neanderthal DNA sequences were acquired from an ancient database, available from before the interstellar era. About 1/3 of them were evaluated as non-functional by the AI and were replaced by predictably designed sequences to achieve maximum similarity in the appearance of a caveman. However, strictly speaking, the Alaloi may look very similar to Neanderthals, but cannot be regarded as such.
Common issues
Despite the great advances in technology, genetic carking is substantially plagued by some difficult-to-predict events. One such is the lack of gene expression. It is not uncommon, due to wrong AI calculations, that one or multiple of the inserted genes are not expressed, or are wrongly expressed in tissue and time.
Another major issue is the unpredicted loss of adaptation due to gene substitution, especially concerning immunity to various diseases, resistance to certain parasites, etc. A clear illustration of this is the lack of immunity of the Alaloi to an otherwise harmless virus, that nearly eradicated most of their tribes when brought by pilot expeditions to their isolated societies.
Finally, the carked humanoid species suffer from low genetic diversity for the newly introduced genes. Generally, the process of genome design does not involve the generation of different alleles of the newly inserted genes, which means, in the case of the Alaloi, all the individuals will be identical in the 0.3% reconstructed genome. As a result, the adaptability to changing environment is reduced, and there is a strong possibility for a gradual population decline.
References
- David Zindell, Neverness (New York: D. I. Fine, 1988)
- David Zindell, The Broken God (HarperCollins, 1992); US ed., Bantam, 1994
- David Zindell, The Wild (Harper Voyager, 1995); US ed., Bantam, 1996
- David Zindell, War in Heaven (Voyager, Bantam, 1998)