Some General Types Of Genes

The Central Dogma of biology, that genes code for protein, led to the general notion that genes specify individual structural proteins and enzymes that control basic physiology. The idea (not always explicitly stated) was that an organism is built up of separate identifiable functions and that one gene coded for one function. We know this is an overstatement, and one that can be quite misleading, but it is a view that has persistent effects on biology and biological research. The traditional kinds of genes, perhaps those most easily understood, code for extracellular structural proteins like collagen, intracellular structural proteins like actins and spectrins, carrier molecules like albumin or hemoglobin, or enzymes that trigger reactions like insulin or hormones, as well as for catalysts of basic energy storage and release or catalysts of reactions in the production and manipulation of basic biomolecules such as nucleic acids, amino acids, carbohydrates such as sugars and starches, cellulose, lipids, steroids and vitamin D derivatives, and so on. Other genes have fundamental roles in controlling DNA packaging and replication and have many general cellular housekeeping functions. Large families of genes exist for these purposes. Such "end-product" genes have each traditionally been associated with a biological function itself and, hence, from an evolutionary point of view, the targets of natural selection. Of course, not one of them acts alone, nor without a chain of cofactors related to their use, protein maturation, expression, and the like.

Such functions are vital to life, and many must have been present in the first cells. But essential as they are, these generic functions are not the focus of this book. We are concerned with the intricate specialized functions of differentiated organisms and the many ways the sequence in DNA works to serve these biological functions. Their discovery has broadened our understanding of how integrated organismal complexity is achieved and evolved and deepens the unifying view that genes are the core functional elements of life. But while the phenogenetic relationships being discovered display logical regularities, they are generally anything but simple.

Genes are discovered in many ways, sometimes by identifying coding sequence and sometimes via effects of mutation or studies of function. One reason that genes can be challenging to classify functionally is that as soon as we think we know what a gene does, other uses and expression may be discovered. Genes originating with one function can evolve others that initially may be related but eventually become at best distantly so. One way this is a problem in scientific practice is that genes are often named for the function for which they were first discovered, which can be very misleading when, as so often happens, diverse additional functions are identified; often, the "original" function is minor or misperceived (e.g., the gene called "eyeless" is not a gene evolved to make—much less remove—eyes but is part of a class of general developmental genes).

Keeping in mind that genes are not necessarily "for" any particular thing (even within a given species), we can at least generally classify them into various functional types, as shown in Figure 7-1. As the figure makes clear, a rather small fraction of genes appear to have "function" in the classical sense. Although not shown in the figure, for each functional group there is a common theme: one or more families of genes descended by gene duplication from a common ancestor, usually with widespread sharing of members of the family among plants, or among animals, or both, and typically also with single-celled organisms. What are some of these types of genes?

Processing Genes

A large class of genes codes for proteins involved in the processing of mRNA or of polypeptides after they have been translated. The processing functions include transport, packaging, error repair, scavenging, activating, inactivating, and modifying proteins or RNA. One interesting example are the heat-shock proteins, often called chaperonins. These genes were discovered because they are expressed under

Functional

Functional

Miscellaneous

10% Metabolic Enzymes

Figure 7-1. Distribution of human gene types based on annotation of human genome sequence. Definitions are rather imprecise and some genes overlap in function. For up to date details see the Gene Ontology website (Gene Ontology Consortium 2003).

Miscellaneous

10% Metabolic Enzymes

Figure 7-1. Distribution of human gene types based on annotation of human genome sequence. Definitions are rather imprecise and some genes overlap in function. For up to date details see the Gene Ontology website (Gene Ontology Consortium 2003).

conditions of stress. Their intracellular functions include the folding and protection of proteins (normally and/or to resist stress of a high-temperature environment, hence "heat shock") and detecting unfolded protein or infection. These genes are found in all major life forms. Perhaps, chaperonins are (or were) also evolutionar-ily primitive intercellular signaling molecules, as they can be found outside of cells and adhere to various cell-surface receptors.

Cell Adhesion and Related or Descendant Function

Multicellular life involves cell-to-cell contact in many ways, as described in Chapter 6. Some of this is achieved with members of a large and ancient family of cell adhesion molecule (CAM) genes.These typically involve a single transmembrane domain and an extracellular domain that binds to a molecule on an adjacent cell, holding the cells together. Some function as homo- or heterodimers (that is, two copies of the same gene product or one or more copies of each of more than one gene product forming a single functional unit). They may also require a cofactor element such as calcium (e.g., cadherins). Desmosomes and adherens junctions that stitch cells together are formed with CAMs.

Most cells in multicellular organisms have CAMs on their surface, so that they can be properly arranged in relation to other cells. This gives the organism its physical architecture. However, not all CAM binding is between cells; integrins can bind to extracellular matrix, for example. Selectins and integrins in some situations facilitate cell shape or movement along a substrate (which can be another cell or a blood vessel, for example).

This ancient class of genes has been involved in the evolution of many functions that would not now perhaps be thought of as simply involving architectural adhesion, but their properties are recognizable and the DNA/protein structure shows the common ancestry. Developing and migrating neurons form bundles that depend in part on a combinatorial cadherin "code," in which cells adhere if they express the same specific set of cadherin gene products. This helps organize neural function (Redies and Puelles 2001). There are also other neural-specific CAMs (called N-CAMs).

These latter genes are members of a large family of immunoglobulin-like CAMs. As will be seen in Chapter 11, the immune system deals with internal damage and foreign molecules by recognition and binding processes that seem to be descendants of simpler cell adhesion phenomena. The immune system recognizes and handles infected or inflamed cells using the CAMs selectins as well as integrins. As things have evolved today, antigen-antibody binding goes beyond cell-cell binding to involve molecular fragments derived from invading cells or molecules. In vertebrates, immunoglobulin-like CAMs include antibody and histocompatibility genes involved in self-non-self recognition.

CAM genes are scattered over the genome, sometimes in large coordinately regulated clusters as in the immunoglobulin and T-cell receptor clusters in mammals.

Cell Environment Control

As described in Chapter 6, cells have pores that enable them to adjust their internal conditions relative to that of adjacent cells and the extracellular space around them. This allows them to keep their internal conditions under control for their particular needs by regulating what goes into and out of the cell. These pores are modular in that they are controlled by different families of genes with different evolutionary histories, although they share the type of functional role they play.

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