| | | How Do The Complications Add Up? |
The possibilities available with a sophisticated network of regulatory genes have not been wasted on multicellular organisms. Our genes are riddled with intricate cross-dependencies, where the product of one gene is used to regulate the product of another. The simplest of triggers can produce results of stunning complexity. For example, it is possible to manipulate a single controlling gene to turn on the formation of eyes in fruit flies. One gene controls the expression of the 2,500 other genes necessary to build an eye.21 Genes are generally triggered by some protein made by some other gene. But here is something interesting: the regulatory proteins controlling an animal's development do not always come from the that animal. Sometimes they come from a parent. And sometimes they come from the environment.
For example, DNA does not encode the location of a fruit fly's head or tail. The location of the embryonic cells destined to become the head or the tail of a fly is determined by an asymmetry to the egg cell engineered by its mother, and operating on what are called "homeobox," or HOX, genes. In flies and other invertebrates, there are "nurse cells" to do this, sitting next to the egg developing within the mother. The nurse cells inject some RNA into the egg cell, and the RNA makes proteins and those proteins bind onto various regulatory regions of the HOX genes in the developing embryo's DNA, and determine how it is to be read, and therefore how regions of the egg differentiate into various body parts. The construction of the nurse cells is, of course, partly determined by DNA, but these nurse cells will help create the sons and daughters of the animal that contains them, not the animal itself. Fruit fly eggs require 15 different nurse cells apiece to add information not already present in the egg's own DNA.22
In vertebrates, there are similar mechanisms to do similar things, though the processes seem more subtle. "Follicle cells" in humans surround the developing egg, adding protein layers and injecting information to be used by the developing embryo. Whatever the process, the result is the egg: a complicated little device, on whose structure an animal's development depends. The "structure" in this case is the variety of building blocks an egg contains -- RNA, proteins, amino acids, nutrients, and the remaining undiscovered what-have-you -- and the relative concentrations of these chemicals in different microscopic regions of that egg. We can think of cell interiors as a soup of cytoplasm, but it's a soup where the noodles and vegetables are all arranged in some pattern and it matters which noodle is where.
And since it's the real world we're talking about, the complications don't end there. The part of the fertilized and already developing fruit fly egg cell that will become the underbelly of the fly is selected by maternal cells next to the embryo.23 These cells release a signalling protein that diffuses across the embryo, and the part with the highest concentration of that protein becomes the new fly's belly. A developing egg doesn't just get nutrition from its mother; it also gets important directions that control its development. There is no "switch" turned on at the moment of fertilization, after which development proceeds autonomously. Fertilization is simply one step among many in the interaction between genes and their environment that eventually produce a new organism. The unsettling part--the aspect that mocks attempts to analyze separate steps of the process--is that in the early stages of development, half of the genes controlling the environment are the same as the ones developing in the egg. The genes control development, but they do it both from within the egg, and from within the parent. The egg needs its genes to develop, but it also needs its mother.
These unexpected features of DNA--mutases, HOX genes, spliceosomes--barely touch the surface of what is known about how cells and DNA behave. We have not mentioned transposable DNA elements, nor horizontal gene transfer, nor the commonly-found overlap between functional units, nor the existence of multiple genetic codes. The framework of the central dogma can hardly support the weight of all its emendations, but there isn't a successor dogma in sight. In a survey of the quandary of molecular genetics, James Shapiro wrote:
That is, it is not useful to talk about the "letters" of DNA making up "words," since many of the words overlap, or are interpreted in different ways by different mechanisms, or if they appear in different places. Under these circumstances, words such as "operon," "coding region" and even "gene" do not indicate specific functional units of DNA, but rather overlapping and shifting assemblies of base pairs. They are, that is, purely conceptual entities, abstractions that help us organize our thoughts about genetics, but without corresponding directly to any underlying physical reality. They are, that is, metaphors.
| | | How Do The Complications Add Up? |