Thursday, April 12, 2018

Epigenesis and epigenetics

Fertilization of the egg by the sperm
In the previous post we saw that at the beginning of the 19th century the theory of epigenesis seemed to have won the game. However, after 1850, and for just over a century, a cascade of new discoveries tipped again the balance towards the theory of preformation. Let us see what they were:
  1. The existence of a nucleus within animal and plant cells.
  2. The confirmation that the nuclei of the male and female gametes are fused during fertilization. This put an end to spermism and ovism and made it clear that the new being begins in the zygote.
  3. The confirmation that certain structures (the chromosomes) appear during cell reproduction inside the nucleus of the cell, which seem to play a very important role. It was also found that in the chromosomal endowment of the zygote, half of the chromosomes come from the father and the other half from the mother.
  4. A new science (Genetics) was originated in the experiments of Thomas Hunt Morgan, who showed that the chromosomes are linked to Mendelian inheritance.
  5. The works of Oswald Avery, who showed that DNA, a nucleic acid that appears in chromosomes, is the basis of Mendelian inheritance.
  6. The discovery of the structure of DNA (a double helix), made in the early 1950’s by Francis Crick, James Watson and Rosalind Franklin.
  7. The deciphering of the genetic code, which took place during the 1950s and the 1960s.
All this gave rise to a new theory of preformation. Of course, no one was looking in the zygote for a perfectly formed homunculus or animaculus, which was replaced by a description encoded in all the DNA contained in the chromosomes.
As a result of these discoveries, in 1958 Francis Crick formulated the Central Dogma of Molecular Biology:
All the information is in the genes. This information can be transferred from nucleic acid to nucleic acid, or from nucleic acid to protein, but never from protein to protein, or from protein to nucleic acid.
A direct consequence of this dogma was the theory of the selfish gene formulated in 1976 by Richard Dawkins. He proposed that multicellular living beings are just the means through which genes, who are the real individuals, can reproduce. This theory was strongly debated by Stephen Jay Gould, but in the early 1990s it seemed to have prevailed.
And yet, by the end of the 90s, a new change of direction had taken place and epigenesis was revived, while the theory of the selfish gene was practically abandoned.
Conrad Hal Waddington
In fact, rather than epigenesis, what has emerged now is a new science, epigenetics, a name proposed in the 1940s by Conrad Hal Waddington, which tries to fuse the ideas of epigenesis with those of preformation. Let us see how:
  • In epigenetics there is a component of the theory of preformation: the genetic information encoded in DNA, which serves as a framework or model for the construction of the new being.
  • But at the same time the Central Dogma of Molecular Biology is denied, since it is expressly stated that not all the information is in the genes.
  • As we learn more about embryonic development, we can see that gene expression (the synthesis of the proteins encoded by the genes) is a much more complex process than was supposed: a process that depends on space and time through genetic regulation:
    • It depends on space, because some genes are expressed in one part of the embryo, but not in another.
    • It depends on time, because some genes are expressed at a certain time during embryonic development, but not in another.
  • In the forefront of the issue is now the problem of genetic regulation: what causes a certain gene to be expressed at a particular time and place and not in another?
    • Sometimes, regulation depends on other genes. We would still be, therefore, under the umbrella of preformation.
    • But some other times it does not seem to depend on the genes of chromosomal DNA, but on other cellular corpuscles, and even on the cytoplasm. Here we would be under the umbrella of epigenesis.
Just now epigenetic reigns supreme. Many things have been discovered regarding embryonic development and genetic regulation, enough to overthrow the Central Dogma. But most of this science is still lost in lack of knowledge, so a future further shift in the theories we are discussing would not be surprising.
Meanwhile, there is some confusion between the concepts of epigenesis and epigenetics. For instance, in the English Wikipedia, in the page allowing to choose between several options for the name Waddington, this text appeared until I corrected it:
Conrad Hal Waddington (1905-75), British biologist who developed the theory of epigenesis
This was a very clear mistake, because Waddington developed epigenetics rather than epigenesis, which was much older (it goes back to Aristotle). In the page dedicated to Waddington, on the contrary, the error was not repeated and the attribution is correct.

The same post in Spanish
Manuel Alfonseca
Second post in a series of four

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