In Chapter 8, I noted that the ease with which Shannon’s information theory applies to molecular biology has sometimes led to confusion about the kind of information contained in DNA and proteins. It may have also created confusion about the places that specified information might reside in organisms. Perhaps because the information-carrying capacity of the gene can be so easily measured, biologists have often treated DNA, RNA, and proteins as the sole repositories of biological information. Neo-Darwinists have assumed that genes possess all the information necessary to specify the form of an animal. They have also assumed that mutations in genes will suffice to generate the new information necessary to build a new form of animal life.9 Yet if biologists understand organismal form as resulting from constraints on the possible arrangements of matter at many levels in the biological hierarchy—from genes and proteins, to cell types and tissues, to organs and body plans—then biological organisms may well exhibit many levels of information-rich structure. Discoveries in developmental biology have confirmed this possibility.
Beyond Genes
Many biologists no longer believe that DNA directs virtually everything happening within the cell. Developmental biologists, in particular, are now discovering more and more ways that crucial information for building body plans is imparted by the form and structure of embryonic cells, including information from both the unfertilized and fertilized egg.
Biologists now refer to these sources of information as “epigenetic.”10 Spemann and Mangold’s experiment is only one of many to suggest that something beyond DNA may be influencing the development of animal body plans. Since the 1980s, developmental and cell biologists such as Brian Goodwin, Wallace Arthur, Stuart Newman, Fred Nijhout, and Harold Franklin have discovered or analyzed many sources of epigenetic information. Even molecular biologists such as Sidney Brenner, who pioneered the idea that genetic programs direct animal development, now insist that the information needed to code for complex biological systems vastly outstrips the information in DNA.11
DNA helps direct protein synthesis. Parts of the DNA molecule also help to regulate the timing and expression of genetic information and the synthesis of various proteins within cells. Yet once proteins are synthesized, they must be arranged into higher-level systems of proteins and structures. Genes and proteins are made from simple building blocks—nucleotide bases and amino acids, respectively—arranged in specific ways. Similarly, distinctive cell types are made of, among other things, systems of specialized proteins. Organs are made of specialized arrangements of cell types and tissues. And body plans comprise specific arrangements of specialized organs. Yet the properties of individual proteins do not fully determine the organization of these higher-level structures and patterns.12 Other sources of information must help arrange individual proteins into systems of proteins, systems of proteins into distinctive cell types, cell types into tissues, and different tissues into organs. And different organs and tissues must be arranged to form body plans.
FIGURE 14.2
The hierarchical layering or arrangement of different sources of information. Note that the information necessary to build the lower-level electronic components does not determine the arrangement of those components on the circuit board or the arrangement of the circuit board and the other parts necessary to make a computer. That requires additional informational inputs.
Two analogies may help clarify the point. At a construction site, builders will make use of many materials: lumber, wires, nails, drywall, piping, and windows. Yet building materials do not determine the floor plan of the house or the arrangement of houses in a neighborhood. Similarly, electronic circuits are composed of many components, such as resistors, capacitors, and transistors. But such lower-level components do not determine their own arrangement in an integrated circuit (see Fig. 14.2).
In a similar way, DNA does not by itself direct how individual proteins are assembled into these larger systems or structures—cell types, tissues, organs, and body plans—during animal development.13 Instead, the three-dimensional structure or spatial architecture of embryonic cells plays important roles in determining bodyplan formation during embryogenesis. Developmental biologists have identified several sources of epigenetic information in these cells.
Cytoskeletal Arrays
Eukaryotic cells have internal skeletons to give them shape and stability. These “cytoskeletons” are made of several different kinds of filaments including those called the “microtubules.” The structure and location of the microtubules in the cytoskeleton influence the patterning and development of embryos. Microtubule “arrays” within embryonic cells help to distribute essential proteins used during development to specific locations in these cells. Once delivered, these proteins perform functions critical to development, but they can only do so if they are delivered to their correct locations with the help of preexisting, precisely structured microtubule or cytoskeletal arrays (see Fig. 14.3). Thus, the precise arrangement of microtubules in the cytoskeleton constitutes a form of critical structural information.
These microtubule arrays are made of proteins called tubulin, which are gene products. Nevertheless, like bricks that can be used to assemble many different structures, the tubulin proteins in the cell’s microtubules are identical to one another. Thus, neither the tubulin subunits, nor the genes that produce them, account for the differences in the shape of the microtubule arrays that distinguish different kinds of embryos and developmental pathways. Instead, the structure of the microtubule array itself is, once again, determined by the location and arrangement of its subunits, not the properties of the subunits themselves. Jonathan Wells explains it this way: “What matters in [embryological] development is the shape and location of microtubule arrays, and the shape and location of a microtubule array is not determined by its units.”14 For this reason, as University of Colorado cell biologist Franklin Harold notes, it is impossible to predict the structure of the cytoskeleton of the cell from the characteristics of the protein constituents that form that structure.15
FIGURE 14.3
Figure 14.3a (left) shows a still shot from an animation of microtubule (at the bottom of the image) made of tubulin proteins. Courtesy Joseph Condeelis. Figure 14.3b (right) shows a microscopic image of a large section of cytoskeleton made of many microtubules (and other elements) inside the cell in cross section. Courtesy The Company of Biologists and Journal of Cell Science.
Another cell structure influences the arrangement of the microtubule arrays and thus the precise structures they form and the functions they perform. In an animal cell, that structure is called the centrosome (literally, “central body”), a microscopic organelle that sits next to the nucleus between cell divisions in an undividing cell. Emanating from the centrosome is the microtubule array that gives a cell its three-dimensional shape and provides internal tracks for the directed transport of organelles and essential molecules to and from the nucleus.16 During cell division the centrosome duplicates itself. The two centrosomes form the poles of the cell-division apparatus, and each daughter cell inherits one of the centrosomes; yet the centrosome contains no DNA.17 Though centrosomes are made of proteins—gene products—the centrosome structure is not determined by genes alone.
Membrane Patterns
Another important source of epigenetic information resides in the two-dimensional patterns of proteins in cell membranes.18 When messenger RNAs are transcribed, their protein products must be transported to the proper locations in embryonic cells in order to function properly. Directed transport involves the cytoskeleton, but it also depends on spatially localized targets in the membrane that are in place before transport occurs. Developmental biologists have shown that these membrane patterns play a crucial role in the embryological development of fruit flies.
Membrane Targets
For example, early embryo development in the fruit fly Drosophila melanogaster requires the regulatory molecules Bicoid and Nanos (among others). The former is required for anterior (head)
development, and the latter is required for posterior (tail) development.19 In the early stages of embryological development, nurse cells pump Bicoid and Nanos RNAs into the egg. (Nurse cells provide the cell that will become the egg—known as the oocyte—and the embryo with maternally encoded messenger RNAs and proteins.) Cytoskeletal arrays then transport these RNAs through the oocyte, where they become attached to specified targets on the inner surface of the egg.20 Once in their proper place—but only then—Bicoid and Nanos play critical roles in organizing the head-to-tail axis of the developing fruit fly. They do this by forming two gradients (or differential concentrations), one with Bicoid protein most concentrated at the anterior end and another with Nanos protein most concentrated at the posterior end.
Insofar as both of these molecules are RNAs—that is, gene products—genetic information plays an important role in this process. Even so, the information contained in the bicoid and nanos genes does not by itself ensure the proper function of the RNAs and proteins for which the genes code. Instead, preexisting membrane targets, already positioned on the inside surface of the egg cell, determine where these molecules will attach and how they will function. These membrane targets provide crucial information—spatial coordinates—for embryological development.
Ion Channels and Electromagnetic Fields
Membrane patterns can also provide epigenetic information by the precise arrangement of ion channels—openings in the cell wall through which charged electrical particles pass in both directions. For example, one type of channel uses a pump powered by the energy-rich molecule ATP to transport three sodium ions out of the cell for every two potassium ions that enter the cell. Since both ions have a charge of plus one (Na+, K+), the net difference sets up an electromagnetic field across the cell membrane.21
Experiments have shown that electromagnetic fields have “morphogenetic” effects—in other words, effects that influence the form of a developing organism. In particular, some experiments have shown that the targeted disturbance of these electric fields disrupts normal development in ways that suggest the fields are controlling morphogenesis.22 Artificially applied electric fields can induce and guide cell migration. There is also evidence that direct current can affect gene expression, meaning internally generated electric fields can provide spatial coordinates that guide embryogenesis.23 Although the ion channels that generate the fields consist of proteins that may be encoded by DNA (just as microtubules consist of subunits encoded by DNA), their pattern in the membrane is not. Thus, in addition to the information in DNA that encodes morphogenetic proteins, the spatial arrangement and distribution of these ion channels influences the development of the animal.
The Sugar Code
Biologists know of an additional source of epigenetic information stored in the arrangement of sugar molecules on the exterior surface of the cell membrane. Sugars can be attached to the lipid molecules that make up the membrane itself (in which case they are called “glycolipids”), or they can be attached to the proteins embedded in the membrane (in which case they are called “glycoproteins”). Since simple sugars can be combined in many more ways than amino acids, which make up proteins, the resulting cell surface patterns can be enormously complex. As biologist Ronald Schnaar explains, “Each [sugar] building block can assume several different positions. It is as if an A could serve as four different letters, depending on whether it was standing upright, turned upside down, or laid on either of its sides. In fact, seven simple sugars can be rearranged to form hundreds of thousands of unique words, most of which have no more than five letters.”24
These sequence-specific information-rich structures influence the arrangement of different cell types during embryological development. Thus, some cell biologists now refer to the arrangements of sugar molecules as the “sugar code” and compare these sequences to the digitally encoded information stored in DNA.25 As biochemist Hans-Joachim Gabius notes, sugars provide a system with “high-density coding” that is “essential to allow cells to communicate efficiently and swiftly through complex surface interactions.”26 According to Gabius, “These [sugar] molecules surpass amino acids and nucleotides by far in information-storing capacity.”27 So the precisely arranged sugar molecules on the surface of cells clearly represent another source of information independent of that stored in DNA base sequences.
Neo-Darwinism and the Challenge of Epigenetic Information
These different sources of epigenetic information in embryonic cells pose an enormous challenge to the sufficiency of the neo-Darwinian mechanism. According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both bodyplan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn’t wholly responsible for the way an embryo develops—for bodyplan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand.
Even in a best-case scenario—one that ignores the immense improbability of generating new genes by mutation and selection—mutations in DNA sequence would merely produce new genetic information. But building a new body plan requires more than just genetic information. It requires both genetic and epigenetic information—information by definition that is not stored in DNA and thus cannot be generated by mutations to the DNA. It follows that the mechanism of natural selection acting on random mutations in DNA cannot by itself generate novel body plans, such as those that first arose in the Cambrian explosion.
Gene-centric Responses
Many of the biological structures that impart important three-dimensional spatial information—such as cytoskeletal arrays and membrane ion channels—are made of proteins. For this reason, some biologists have insisted that the genetic information in DNA that codes for these proteins does account for the spatial information in these various structures after all. In each case, however, this exclusively “gene-centric” view of the location of biological information—and the origin of biological form—has proven inadequate.
First, in at least the case of the sugar molecules on the cell surface, gene products play no direct role. Genetic information produces proteins and RNA molecules, not sugars and carbohydrates. Of course, important glycoproteins and glycolipids (sugar-protein and sugar-fat composite molecules) are modified as the result of biosynthetic pathways involving networks of proteins. Nevertheless, the genetic information that generates the proteins in these pathways only determines the function and structure of the individual proteins; it does not specify the coordinated interaction between the proteins in the pathways that result in the modification of sugars.28
More important, the location of specific sugar molecules on the exterior surface of embryonic cells plays a critical role in the function that these sugar molecules play in intercellular communication and arrangement. Yet their location is not determined by the genes that code for the proteins to which these sugar molecules might be attached. Instead, research suggests that protein patterns in the cell membrane are transmitted directly from parent membrane to daughter membrane during cell division rather than as a result of gene expression in each new generation of cells.29 Since the sugar molecules on the exterior of the cell membrane are attached to proteins and lipids, it follows that their position and arrangement probably result from membrane-to-membrane transmission as well.
Consider next the membrane targets that play a crucial role in embryological development by attracting morphogenetic molecules to specific places on the inner surface of the cell. These membrane targets consist largely of proteins, most of which are mainly specified by DNA. Even so, many “intrinsically disord
ered”30 proteins fold differently depending on the surrounding cellular context. This context thus provides epigenetic information. Further, many membrane targets include more than one protein, and these multiprotein structures do not automatically self-organize to form properly structured targets.31 Finally, it is not only the molecular structure of these membrane targets, but also their specific location and distribution that determines their function. Yet the location of these targets on the inner surface of the cell is not determined by the gene products out of which they are made any more than, for example, the locations of the bridges across the River Seine in Paris are determined by the properties of the stones out of which they are made.
Similarly, the sodium-potassium ion pumps in cell membranes are indeed made of proteins. Nevertheless, it is, again, the location and distribution of those channels and pumps in the cell membrane that establish the contours of the electromagnetic field that, in turn, influence embryological development. The protein constituents of these channels do not determine where the ion channels are located.
Like membrane targets and ion channels, microtubules are also made of many protein subunits, themselves undeniably the products of genetic information. In the case of microtubule arrays, defenders of the gene-centric view do not claim that individual tubulin proteins determine the structure of these arrays. Nevertheless, some have suggested that other proteins, or suites of proteins, acting in concert could determine such higher-level form. For example, some biologists have noted that so-called helper proteins—which are gene products—called “microtubule associated proteins” (MAPs) help to assemble the tubulin subunits in the microtubule arrays.
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