Parthenogenesis: undivided motherhood

Oleg Makarov, Popular Mechanics magazine No. 3-2009
(the editorial board expresses its gratitude to the Eternal Youth website www.vechnayamolodost.rufor help in writing the article)

Most of the living world is divided in half. By the sexes. The gender is female and the gender is male. By making the production of offspring a matter of two individuals instead of one, nature has made a step forward, since the mixing of genetic material gives a chance for the emergence of more viable organisms. But there is also a way back. Sometimes, for various reasons, a female, giving birth to offspring, does, so to speak, without a dad…

This phenomenon is called "parthenogenesis" from two Greek words παρθενος – virgin and γενεσις – birth. Generally speaking, we have known since childhood that new living organisms may well arise without any stamens and pistils. A strawberry bush, spreading whiskers on the bed, will grow offspring in the form of exactly the same bushes, a branch stuck in the ground (the fashionable word "clone" in Greek is "stalk") will turn into a new tree…

Historically, asexual reproduction that preceded sexual reproduction is based on the process of mitosis, a simple division of a living cell. As a result, two cells with the same set of genes are formed – exact copies of the parent, preserving, figuratively speaking, all its virtues and vices. Changes from generation to generation can only occur as a result of genetic mutations.  True, microbes adapt perfectly to changing environmental conditions such as exposure to antibiotics, but they take the number and speed of reproduction. And even they have something like a sexual process - the exchange of genes between cells of the same, and sometimes completely different species. And in the vast majority of plants and the most primitive representatives of the animal kingdom (like earthworms and starfish), capable of vegetative reproduction, it complements, but does not replace the sexual process.

Nature's Game

During sexual reproduction, the blueprint of a new organism embedded in its DNA is created by a random combination of the genetic material of two parents. The dice are thrown on the table. What combination will come out in the end, increasing or decreasing the chances of winning in the struggle for existence is a matter of chance, but without constant shuffling of genes and selection of their optimal combinations, complex multicellular organisms would not be able to evolve.

If we continue the association with gambling, the genome of eukaryotic (having a cell nucleus) organisms, from yeast to humans, is made up of two "decks" – paired genes (alleles) located on paired chromosomes. Somatic (bodily, from Greek. "soma" – body) cells during the growth of the organism and the replacement of dead cells multiply by the same simple division – mitosis, in which a set of chromosomes is transmitted unchanged from the parent cell to the daughter. Mutations in somatic cells can lead to various (usually unpleasant) consequences, but they are not transmitted to the next generation.

Germ cells are formed as a result of a much more complex process of division – meiosis, in which primary germ cells – oogonia (female) and spermatogonia (male) are formed into eggs and spermatozoa, respectively. In this case, the diploid (carrying a complete set of genetic information in two pairs of chromosomes) primary germ cell turns into a haploid, with one chromosome from each pair and, accordingly, one from each pair of parental genes. During meiosis, paired chromosomes exchange sites, and each egg or sperm gets a random set of genes received from the grandparents of the future baby (or butterfly, flower, and any other sexually reproducible organism). Two germ cells merge into one – a zygote, which some time later will begin to divide in a mitotic way, developing into an embryo. But an unfertilized egg can also begin to divide – this is what is called parthenogenesis. It should be clarified immediately: parthenogenesis is not asexual reproduction, but a kind of sexual (with its inherent biological processes), however, with the participation of only female germ cells.

Chaste rotifers

Parthenogenesis in wildlife is not something exceptional. Rotifers – tiny (from 40 microns to 2 mm) inhabitants of freshwater reservoirs, allocated in taxonomy to a separate type of the kingdom "Animals" – have been represented for 40 million years only by female individuals producing offspring exclusively by parthenogenesis. With all the progressiveness of sexual reproduction, the option with the origin of offspring from one individual has its advantages. For example, when the environment is conducive to rapid reproduction of a species and there is enough food around for numerous offspring, parthenogenesis gives a gain in the rate of colonization of this environment. In this case, it is possible to sacrifice genetic diversity (the offspring carries only the mother's chromosomes), but to mobilize the entire potential of the species for reproduction. When conditions change unfavorably, natural selection will weed out less adapted organisms. But rotifers are rather an exception to the rule. In many species of plants, arthropods, amphibians, reptiles and even birds, there is not an obligate (mandatory) form of parthenogenesis, but an optional one – under suitable circumstances. For example, in some aphid species, the transition to parthenogenesis and back has the character of seasonal fluctuations.

The longing shark

It is surprising, however, that sometimes species of living organisms resort to parthenogenesis, which previously, as they say, were not noticed in this. In recent years, several striking cases of parthenogenesis have been described in sharks, in which parthenogenesis has never been observed before. In 2001, at the Henry Doorly Zoo in Nebraska (USA), a small-headed hammerhead fish (small–headed is a species name, not a teaser) gave birth to a cub after a long stay in a water tank where there were no males. This "immaculate conception" initially baffled scientists. Among others, the option of long–term preservation of sperm from long-standing sexual contact was considered - such a phenomenon of "false parthenogenesis" is sometimes observed in nature. An accident helped to dot the "I": the grown cub died from a stingray injection. The result of the DNA analysis clearly showed that there was no genetic material in the cells of the cub, except for the mother. A certain program hidden in the shark's DNA, which in natural conditions reproduces exclusively through fertilization, turned on a reserve mechanism for preserving the species – parthenogenesis. Thus, the reason for parthenogenetic reproduction may also be the absence of males, for example, at the border of the species' range.

A similar case occurred in 2002 at the Detroit Aquarium (USA), and then in Hungary. In 2006, a parthenogenetic cub hatched from an egg of a female Commodus monitor lizard at the London Zoo. In the wild, Commodus monitor lizards were also not seen to be prone to parthenogenesis.

However, is it possible to say that these cubs were clones, an exact genetic copy of the maternal organisms? No, in this case it is not.

The fact is that biologically parthenogenesis is carried out mainly in two ways. One of them is that the primary female germ cell, without going through the stage of meiosis, begins to divide mitotically, creating its own copy. In the case of highly developed animals, an egg obtained during meiosis, which, as we remember, has a haploid – half–set of chromosomes, merges with another egg, also with a half, but differently combined set of "grandmother" and "grandfather" chromosomes. In both cases, due to the shuffling of gene alleles that occurs during the formation of a haploid egg, the genotype and the properties determined by it of an organism born with the help of parthenogenesis will differ to one degree or another from the maternal one.

Both sharks and monitor lizards had female parthenogenetic cubs, which is natural for living organisms in which the male sex is transmitted through the Y chromosome, located only in male germ cells. In some species of living beings, the inheritance of sex is carried out differently: for example, in one of the breeds of turkeys, many eggs develop parthenogenetically, and only males appear from them. In bees and ants, parthenogenesis is used to regulate the sex ratio: females develop from fertilized eggs, and males develop from unfertilized eggs. And some species of bony fish "seduce" males of another species. At the same time, the sperm does not penetrate into the egg, but only stimulates the doubling of its chromosomes and division.

God's Rivals

In the discussion of parthenogenesis, the theme of one of the main tenets of Christianity inevitably pops up – the immaculate conception of the Virgin Mary. Do the gospel traditions not keep a certificate of the parthenogenetic birth of a person? But in this case, the baby would have to be born a girl due to the absence of Y chromosomes in the egg, and participation in the immaculate conception of St. The spirit is not within the competence of science. However, if we take the intervention of supernatural forces out of the brackets, then not only man, but also any other mammal is incapable of "immaculate conception". On the path of human parthenogenesis, nature has erected a powerful barrier, whose name is genomic imprinting.

The meaning of this tricky term is that for a developing mammalian embryo, figuratively speaking, it does not matter from whom this or that gene came – from mom or dad. The gene responsible for the development of some vital organ will simply not manifest itself if it has the wrong sex marker. That is why, even if the mammalian egg begins to divide, say, under the influence of some external stimuli, there is no chance that a viable organism will be born as a result. Genomic imprinting will block the development of the embryo in the early stages. Unless, of course, genetic engineering gets involved.

Scientists from the Tokyo Agricultural University managed to achieve the first parthenogenetic birth of mammals in 2004. The Japanese applied the technology of haploidization developed by them, that is, the artificial (without meiosis) transformation of somatic cells of a female mouse into haploid (similar to either male or female gametes) cells. Then, under laboratory conditions, it was possible to achieve the fusion of these cells by "deceiving" genomic imprinting with the help of special technologies. And finally, already in the mother's body, the embryo began to develop from the cell.

The figures show how difficult it was for geneticists to interfere in the holy of holies of wildlife. About 500 artificially haploidized cells made it possible to cause a total of 24 pregnancies, of which only two resulted in childbirth. Only one cub managed to develop into a full-fledged organism. However, to begin with, the result is not so bad: Dolly the sheep had almost 300 sisters at the stage of a fertilized egg.

Just fantastic

Cloning primates due to the peculiarities of the development of their fertilized eggs during the very first divisions is still technically impossible. And no serious scientist has set himself the task of human reproductive cloning. Numerous attempts to learn how to grow human embryos by the method of cell nucleus transfer – the same one with which Dolly was born – are needed for therapeutic cloning.

The trailblazer conman
Therapeutic cloning is associated with one of the largest scientific scandals in recent years. In February 2004, Science magazine published an article by one of the leading experts in the field of cloning, Korean scientist U-Suk Hwan and his colleagues, about a sensational result: for the first time in the world, a cloned human embryo was obtained from which a viable stem cell culture was isolated. In May 2005, a second sensation appeared in the same Science – about the creation in Hwang's laboratory of eleven lines of human embryonic stem cells, also obtained by the somatic cell nucleus transfer method. And already at the end of the year, first rumors began to spread among scientists and journalists, then well–founded suspicions… In the end, Hwang admitted that all these results were falsified, resigned from all official posts, and in a televised speech apologized to the scientific community and the Korean people. However, under his leadership, work continues on cloning animals – but in private companies.

At the same time, as with the production of embryonic stem cell cultures from the "waste" of in vitro fertilization – fertilized eggs in reserve, an embryo from an egg cell with a transplanted donor nucleus is supposed to be destroyed at an early stage. Such cells will not be rejected during cell therapy and transplantation of the nucleus of tissues made from them and even whole organs to the donor. But both work with ordinary cells of human embryos, and any, even therapeutic, cloning of human cells cause resistance from religious fundamentalists and other guardians of morality. This is one of the reasons why some specialists have tried to go roundabout ways, for example, to obtain chimeric embryos from the nucleus of a human somatic cell and an egg cell of a cow or rabbit. All these roundabout paths led to dead ends, except for one: in July 2007, a group of scientists from the Moscow Center of Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences and the American corporation Lifeline Cell Technology managed to grow 6 lines of polypotent (capable, like embryonic, of turning into any body tissue) stem cells from unfertilized human eggs. The achievement is impressive, although this method can be used to obtain therapeutic cell cultures only for women of childbearing age. And, it seems, this direction will not develop: already in November of the same 2007, two groups of scientists – from Wisconsin and Kyoto University – simultaneously announced the development of methods for obtaining artificially induced pluripotent stem cells (iPSC) from fibroblasts, ordinary skin cells. In order for adult cells to "fall into childhood", they had to be injected with working copies of four genes active during embryonic development and blocked in the adult body with the help of a viral carrier. The new technique has already been tested in many laboratories, and in February 2009 human iPSCs were used for the first time to repair damaged spinal cord – so far in mice, but it is hoped that in a few years it will come to the first clinical trials in humans.

Perhaps it is these experiments that will put a bold end to bioethical disputes, leaving the topic of parthenogenesis to the authors of fantasy novels that portend the emergence of a world without men. Fortunately, it doesn't look like women are really striving for such a world yet.

Portal "Eternal youth" www.vechnayamolodost.ru11.03.2009