Genetic cloning (forming a new organism by using the DNA of somatic cells) is among the key events in the last centrury that broke new ground in life sciences. Starting with the sheep (Dolly),Citation1 this venture has been extended to include many other living things (i.e. pigs, goats, horses, cats, etc)., and will continue to do so.Citation2,Citation3 In cloning, the genetic material (DNA) from the gamete (oocyte) of the organism to be cloned is removed and transplanted with the genetic material (DNA) obtained from the somatic cells of the organism (male or female).Citation1,Citation2 Next the oocyte is placed into the uterus to let the normal development proceed resulting in birth of the offspring.Citation1 However, the age of the offspring is the sum of the time the organism spent in the mother's womb and the age of the organism from whom the somatic cell was obtained (male or female whose somatic cell was used).Citation3
Supposedly, given that this new organism has the identical genetic material of the ancestor from whom it was obtained (from the somatic cells of the female or male), it is said to be identical i.e., a clone. However this is not necessarily correct. Just like sex cells, somatic cells have transposable elements (TEs or transposons).Citation4 TEs cause mutations in both prokaryotes and eukaryotes as a result of their mobility. About 50% of the human genome is composed of TEs.Citation5 Consequently, given that genomes have these TEs, the DNA nucleotide sequence of any 2 organ or tissue cells cannot be the same unless transposition absent. In other words, when somatic cells are genetically cloned, no 2 cells can be expected to have the exactly same expansion of the DNA information. The genomes of nearly all organisms contain transposons that can move from one position in the genome to another by either a transpositional or a conservative site-specific recombination process" including human body that composed of 75 trillion cells. Thus, even if the DNA of the same cells of the tissue is used, the clone may not be identical to the original due to transposons. Although ethical rules and laws have not allowed human cloning around the world, when human cloning becomes possible in the future, the following information should be kept in mind.
The human genome has a vast number of transposons.Citation4,Citation5 The major transposons include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). LINEs are about 6 kb-long, can be found in as many copies as 850,000 and cover the 21% of the human genome. SINEs, on the other hand, are about 100 to 500 base pairs in length.Citation5 The human genome includes 1.5 million copies of SINEs, which make up about 13% of the genome.Citation5 The remaining transposon families form about 11% of the human genome, which have an ability to create mutations. LINEs, for instance, can be inserted into the dystrophin gene. That will result in frameshift mutation and premature cessation of dystrophin protein translation. SINEs (Alu element, for instance),Citation5,Citation6 can be inserted into BRCA2 gene leading to loss of function of this tumor-suppressing gene. The patient will show increased disposition to breast cancer. As these examples broadly indicate, the DNA of the somatic cells can have differing sequences.Citation7
It is also well-known that the lifespan of the cells of every organ is limited. Therefore, organs are continuously renewed over time. During this renewal process, some of the cells undergo mutations due to various reasons; and thus, they can have neither the same genetic material nor the same DNA sequence. One day, when human cloning from somatic cells presents itself as a possibility, it will be useful to take mutations caused by transposons into consideration. It should be remembered that these transposons are mobile DNA segments which may preclude identical genetic cloning.
Abbreviations
| DNA | = | DNA (genetic material) |
| LINEs | = | Long interspersed nuclear elements |
| SINEs | = | Short interspersed nuclear elements |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
References
- Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature 1997; 385:810-3; PMID:9039911; https://doi.org/10.1038/385810a0
- Prather RS. Cloning. Pigs is pigs. Science 2000; 289:1886-7; PMID:11012362; https://doi.org/10.1126/science.289.5486.1886
- García-Sancho M. Animal breeding in the age of biotechnology: the investigative pathway behind the cloning of Dolly the sheep. Hist Philos Life Sci 2015; 37:282-304; PMID:26205201; https://doi.org/10.1007/s40656-015-0078-6
- Collier LS, Largaespada DA. Transposable elements and the dynamic somatic genome. Genome Biol 2007; 8(Suppl 1):S5; PMID:18047697; https://doi.org/10.1186/gb-2007-8-s1-s5
- Callinan PA, Batzer MA. Retrotransposable elements and human disease. Genome Dyn 2006; 1:104-15; PMID:18724056
- Cordaux R, Hedges DJ, Herke SW, Batzer MA. Estimating the retrotransposition rate of human Alu elements. Gene 2006; 373:134-7; PMID:16522357; https://doi.org/10.1016/j.gene.2006.01.019
- Belancio VP, Hedges DJ, Deininger P. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res 2008; 18:343-58; PMID:18256243; https://doi.org/10.1101/gr.5558208