There Are Many Forms of Information in DNA

KEY CONCEPTS
-Genetic information includes not only that related to characters corresponding to the conventional phenotype but also that related to characters (pressures) corresponding to the genome “phenotype.”
-In certain contexts, the definition of the gene can be seen as reversed from “one gene–one protein” to “one protein–one gene.”
-Positional information might be important in development.
-Sequences transferred “horizontally” from other species to the germ line could land in introns or intergenic DNA and then transfer “vertically” through the generations. Some of these sequences might be involved in intracellular non-self-recognition.
The term genetic information can include all information that passes “vertically” through the germ line, not just genic information. The word “gene” and its adjective “genic” have different meanings in different contexts, but in most circumstances there is little confusion when context is considered. For situations in which a sequence of DNA is responsible for production of one particular polypeptide, 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 sequences encoding polypeptides overlap or have alternative forms of expression, we can reverse the usual description of the gene. Instead of saying “one gene–one polypeptide,” we can describe the relationship as “one polypeptide–one gene.” So we regard the sequence involved in production of the polypeptide (including introns and exons) as constituting the gene, while recognizing that part of this same sequence also belongs to the gene of another polypeptide. This allows the use of descriptions such as “overlapping” or “alternative” genes.
We can now see how far we have come from the one gene–one enzyme hypothesis of the 20th century. The driving question at that time was the nature of the gene. It was thought that genes
represented “ferments” (enzymes), but what was the fundamental nature of ferments? After it was discovered that most genes encode proteins, the paradigm became fixed as the concept that
every genetic unit functions through the synthesis of a particular protein. Either directly or indirectly, protein-encoding pressure was responsible for what we can now refer to as the conventional phenotype. We now recognize that genetic units encoding polypeptides can also include information corresponding to the genome phenotype, manifestations of which include fold pressure, purine-loading (AG) pressure, and GC pressure.
There can be conflict between different pressures, such as competition for space in the gamete that will transfer genomic information to the next generation. For example, a protein might function most efficiently with the basic amino acid lysine (codon AAA) in a certain position, but GC pressure might require the substitution of another basic amino acid, such as arginine (codon CGG). Alternatively, fold pressure might require the corresponding nucleic acid to fold into a stem-loop structure in which CCG would pair with the antiparallel arginine codon. A lysine codon in this position would disrupt the structure, so again a less efficient polypeptide would need to suffice.
The conventional phenotype, however, remains the central paradigm of molecular biology: a genic DNA sequence either directly encodes a particular polypeptide or is adjacent to the segment that actually encodes that polypeptide. How far does this paradigm take us beyond explaining the basic relationship between genes and proteins?
The development of multicellular organisms required 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 beginning 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 of the tissues of the adult are formed and functioning. The molecular nature of this regulatory network is still under investigation, but we see that it consists of genes that encode products (often protein, but sometimes RNA) that can influence the expression of other genes.
Although 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 fully understand how these particular regions are formed, though particular examples have been well studied . We assume, however, that the existence of positional information in the egg leads to the differential expression of genes in the cells making up the tissues formed from these regions. This leads to the development of the adult organism, which in the next generation leads to the development of an egg with the appropriate positional information.
This possibility of positional information suggests that 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 might be needed to perpetuate the positional information). Put in a more general way, we might ask the following: If we have 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?
After tissues and organs have developed, they not only must be maintained but also protected against potential pathogens. Groups of variable genes have diversified in the germ line, and continue to diversify somatically, to allow multicellular organisms to (1) respond extracellularly by the synthesis of immunoglobulin antibodies directed against pathogens, and (2) “remember” past pathogens so that future responses will be faster and stronger (immunological memory; see the chapter titled Somatic DNA Recombination and Hypermutation in the Immune System). Should it escape such extracellular defenses, though, the nucleic acid of a pathogenic virus could gain entry to cells and intracellular defenses would be needed.
We know that in bacteria infected by bacteriophages , host defenses include rapid local or genome-wide transcription of DNA (which has been documented in eukaryotes in response to environmental insult or infection) to produce “antisense” transcripts that are capable of base-pairing with pathogen “sense” transcripts to form double-stranded RNAs.
These RNAs then act as an alarm signal to trigger secondary defenses . The host could store a “memory” of previous intracellular invaders by converting some pathogen transcripts into DNA through reverse transcription and inserting them into its genome in an inactive form for future rapid transcription of antisense RNAs in times of active infection by that pathogen. Thus, some pathogen nucleic acid might enter the germline “horizontally” (within a generation) and the parental memory of the pathogen could subsequently be transferred “vertically” to offspring. The diversity of some elements found within introns and extragenic DNA (see the chapter titled Transposable Elements and Retroviruses) could in part reflect such past pathogen attacks. There is recent evidence of such inherited antiviral immunity in several animal and plant species.