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Is all genetic information contained in DNA?


KEY TERMS:
  • Positional information describes the localization of macromolecules at particular places in an embryo. The localization may itself be a form of information that is inherited.
KEY CONCEPTS:
  • The definition of the gene has reversed from "one gene : one protein" to "one protein : one gene".
  • Positional information is also important in development. 

The concept of the gene has evolved significantly in the past few years. The question of what's in a name is especially appropriate for the gene. We can no longer say that a gene is a sequence of DNA that continuously and uniquely codes for a particular protein. In situations in which a stretch of DNA is responsible for production of one particular protein, current usage regards the entire sequence of DNA, from the first point represented in the messenger RNA to the last point corresponding to its end, as comprising the "gene," exons, introns, and all.
When the sequences representing proteins overlap or have alternative forms of expression, we may reverse the usual description of the gene. Instead of saying "one gene-one polypeptide," we may describe the relationship as "one polypeptide-one gene." So we regard the sequence actually responsible for production of the polypeptide (including introns as well as exons) as constituting the gene, while recognizing that from the perspective of another protein, part of this same sequence also belongs to its gene. This allows the use of descriptions such as "overlapping" or "alternative" genes.
We can now see how far we have come from the original one gene : one enzyme hypothesis. Up to that time, the driving question was the nature of the gene. Once it was discovered that genes represent proteins, the paradigm became fixed in the form of the concept that every genetic unit functions through the synthesis of a particular protein.
This view remains the central paradigm of molecular biology: a sequence of DNA functions either by directly coding for a particular protein or by being necessary for the use of an adjacent segment that actually codes for the protein. How far does this paradigm take us beyond explaining the basic relationship between genes and proteins?
The development of multicellular organisms rests on the use of different genes to generate the different cell phenotypes of each tissue. The expression of genes is determined by a regulatory network that takes the form of a cascade. Expression of the first set of genes at the start of embryonic development leads to expression of the genes involved in the next stage of development, which in turn leads to a further stage, and so on until all the tissues of the adult are functioning. The molecular nature of this regulatory network is largely unknown, but we assume that it consists of genes that code for products (probably protein, perhaps sometimes RNA) that act on other genes.
While such a series of interactions is almost certainly the means by which the developmental program is executed, we can ask whether it is entirely sufficient. One specific question concerns the nature and role of positional information. We know that all parts of a fertilized egg are not equal; one of the features responsible for development of different tissue parts from different regions of the egg is location of information (presumably specific macromolecules) within the cell.
We do not know how these particular regions are formed. But we may speculate that the existence of positional information in the egg leads to the differential expression of genes in the cells subsequently formed in these regions, which leads to the development of the adult organism, which leads to the development of an egg with the appropriate positional information
This possibility prompts us to ask whether some information needed for development of the organism is contained in a form that we cannot directly attribute to a sequence of DNA (although the expression of particular sequences may be needed to perpetuate the positional information). Put in a more general way, we might ask: when we read out the entire sequence of DNA comprising the genome of some organism and interpret it in terms of proteins and regulatory regions, could we in principle construct an organism (or even a single living cell) by controlled expression of the proper genes?

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