The inherited causal elements were given the name “genes” early in the twentieth century, but it took many decades to understand where in the cell these causal elements are located and what their nature is. A fundamental finding was that genes are individual molecules rather than ready-formed miniature parts of organs. Individual genes were identified because their variation was associated with variation in some trait—much of the work was done in fruit flies, which are easy, cheap, and fast to manage in the laboratory, and had many easily recognized variable traits. It was shown that these genes were segments strung along super-size molecules called “chromosomes,” located in the nucleus of cells.
The chromosomes are long molecules of DNA (deoxyribonucleic acid), and DNA is made up of four different kinds of units, called nucleotides, and denoted A, C, G, and T (derived from their chemical names). These are strung together in a chain to make up a chromosome. Each species has a characteristic number of chromosomes, and that set is known as the organism’s “genome.” And with some minor exceptions, each cell in an organism contains two copies of its genome, one inherited from each parent. When cells divide into two “daughter” cells, both copies of the genome are themselves copied, and one set is transmitted to each daughter cell.
By the middle of the century, detailed analysis of this peculiar kind of very large molecule had revealed that individual genes consisted of sections of this string. And this fact led to an understanding of the basic functional nature of genes: as expressed in terms appropriate to our computer age, these molecules carry information.
The first important point is that the length of the chromosome is not constrained chemically and can be hundreds of millions of nucleotides long. Secondly, the order of the nucleotides is also not constrained. What this means is that regions, or substrings, have functions that depend on the order of their nucleotides. From mushrooms to mankind, the same system works—because it all ultimately descended from ancient common ancestry in the history of life, and because the flexibility of nucleotide order allows for information to be carried that differs from species to species throughout the living world.
This works for two major reasons. First, is that the order of nucleotides along chromosomes provides a code that is used to assemble strings of other units, called amino acids. Strings of amino acids are known as proteins, and once they are assembled, they fold up upon themselves (for chemical reasons), and their folded shape determines what other molecules, including other proteins, they will interact with—basically, that they will stick to, one perhaps altering the other in the process. Much of what makes life is the interaction of many different types of proteins within cells and on the cells’ surfaces. It is the particular set of elements, including proteins, that is in or on a cell that determines what kind of cell it will be: kidney or skin, flower or leaf, insect wing or leg, animal brain or bone, or a humble bacterium or fungus.
The protein-coding part of DNA is copied, or transcribed into an intermediate molecule called RNA that has the same sequence as that part of the DNA, but in the cell is grabbed by specific organelles called “ribosomes,” which translate the code by assembling the code-specified amino acids, one by one, in the same order as the nucleotide code copied from DNA, into the protein being specified. The genome of each species contains the code for all of the proteins—usually numbering in the tens of thousands—which that species needs to make.
This leaves an obvious question unanswered. What makes an organism like a tree, snail, bird, or human is that we are differentiated into many different structures and organs. For example, we have lungs, brains, fingers, and stomachs. So if each cell contains the very same genome for its species, what can this have to do with its differentiated structure that makes the species what it is? The answer is that although each cell inherits the entire genome, what makes it have its specific traits is that it only uses some of its genes, while the other genes remain silent—they are not used to code for their respective protein in that cell. And this points to the second major function of DNA. Short strings of nucleotides called “regulatory elements” are used not to code for protein but to control whether a nearby protein-coding gene will be used in a given cell. These regulatory sequences in DNA are chemically recognized by specific proteins called “transcription factors” (TFs) that the cell has already produced (being coded by genes somewhere else in the genome). The TF molecule physically recognizes the regulatory element and grabs on to it. This binding event (more accurately, similar events by multiple proteins attaching to regulatory elements and to each other) then causes a nearby gene to be transcribed into RNA, and hence translated into protein, and hence used by the cell to determine the cell’s particular nature.
We have one more piece of the differentiation puzzle to describe in order to understand the intelligence of the egg, or any other cell for that matter. If a cell’s nature is determined largely by the set of its genes that it is using, what determines that? The answer, in brief, is signaling, or the transfer of information among cells. Among the proteins that a cell makes, besides various TFs, are additional sets of proteins called “signal molecules” and “signal receptors.” Signal molecules are secreted from the cell, where they can drift or be carried in the circulation to other places in the body. Signal receptors are molecules that can detect and respond to signal molecules, binding with them much as a key fits into a lock. When that happens, it triggers a chain of interactions inside the cell that causes specific TFs to be activated and in turn to cause specific genes to be expressed. Signals can also come from other sources such as environmental sensory input or dietary elements. From the time of fertilization onward, the development of an animal or plant embryo is a cascading sequence of changing cell differentiation, based on this kind of signaling.
What we now know is that it’s the specific combinations and timing of signal-sending and detection that determine which cells will take on which functions as the embryo develops its various organs, and as the organisms works their way through life. This is shown in Fig. 3. One combination for stem, another for leaf; one for brain, another for braincase: very different tissues, but the same genome. Symbolically in the figure, signals are represented as circles, triangles, or +’s. A cell expressing, say, a circle-receptor can detect the presence of circle-signals passing by, and when the receptor binds the signal the cell ‘knows’ about this event. If the cell does not present the receptor, as for ‘+’ in the figure, it simply doesn’t know the signal is out there, and cannot respond to it.
Life is all about cells, and cells are largely about signaling. As illustrated in Fig. 4, a cell is like the CIA headquarters: it has all sorts of internal, partly self-sufficient departments, with communications among their various members (the intelligence agents), but it is largely sealed from the outside word—an ordinary citizen can’t just wander in and roam around the place! At the same time, its roof is bristling with antennae, because its job is to monitor the world and respond to it. And it releases agents (signals) to pass information to allies elsewhere.
In the CIA, this is accomplished by electronics to detect signals and by agents exported to go out and pass information to other agents. In the cell, a partially sequestered internally structured environment, this information exchange is accomplished because the DNA in the inherited genome includes all the genes that code for all of the required proteins, including signal molecules, their signal receptors, and all the subsequent interacting molecules, including transcription factors that switch on other genes. Development and maintenance of the body during life are just the history of switching genes on and off, at each stage dependent on the signaling environment, which can include all sorts of signals from other cells, and from the broader environment that cells detect. Indeed, the same kinds of mechanisms are responsible for the interaction of members of a given species, or of individuals with their environment: light, odors, temperature, sounds, and so on are all used as signals for cells to detect and respond to.
Since our culture is in love with computers these days, we have a tendency to think of the information contained in genomes as a kind of self-contained computer program for the organism. But this is not the whole story, among other reasons because a program has a beginning and an end while an organism is a continuation of the cellular life of its parents. A fertilized egg can differentiate into an organism only because of the complex mix of proteins and other molecules that the egg contains along with its genome, and those ingredients determine which of the egg’s genes will be used in its first stages, including signals being sent and received, so that subsequent stages can take place. Thus, your life was a beginning of you as an organism, but a continuation of the lives of both your parents—and their parents, and their parents, ad infinitum—all the way back to the origin of life itself—when we think that somehow spontaneous generation really did occur.
There are a couple of other important facts about how signaling allows our humble egg to turn into a sometimes not-so-humble adult. First, it is the combination rather than the physical properties of the sets of signals that causes cells to change. The signal is information, but its properties are not miniatures of what the cell will become. Referring metaphorically to Fig. 3, there is nothing “round” about the triangle signal that makes a cell become more round! Secondly, many if not most, signals are used in multiple parts of a developing body. This means that the combination is what we call functionally arbitrary. Again referring to the Figure, the “triangle” and “circle” signals (but in varying combinations) are used in multiple parts of the body. Thus, they comprise a limited repertoire of signals but produce an open-ended set of differing results.
In a nutshell: life is signaling.