As discussed in Chapter 1, the DNA in genomes does not direct protein synthesis itself, but instead uses RNA as an intermediary. When the cell needs a particular protein, the nucleotide sequence of the appropriate portion of the immensely long DNA molecule in a chromosome is first copied into RNA (a process called transcription). It is these RNA copies of segments of the DNA that are used directly as templates to direct the synthesis of the protein (a process called translation). The flow of genetic information in cells is therefore from DNA to RNA to protein (Figure 6–1). All cells, from bacteria to humans, express their genetic information in this way—a principle so fundamental that it is termed the central dogma of molecular biology. Despite the universality of the central dogma of molecular biology, there are important variations between organisms in the way in which information flows from DNA to protein. Principal among these is that RNA transcripts in eukaryotic cells are subject to a series of processing steps in the nucleus, including RNA splicing, before they are permitted to exit from the nucleus and be translated into protein. As we discuss in this chapter, these processing steps can critically change the “meaning” of an RNA molecule and are therefore crucial for understanding how eukaryotic cells read their genome.
Although we focus on the production of the proteins encoded by the genome in this chapter, we see that for many genes, RNA is the final product. Like proteins, some of these RNAs fold into precise three-dimensional structures that have structural and catalytic roles in the cell. Other RNAs, as we discuss in the next chapter, act primarily as regulators of gene expression. But the roles of many non-coding RNAs are not yet known.
One might have predicted that the information present in genomes would be arranged in an orderly fashion, resembling a dictionary or a telephone directory. But it turns out that the genomes of most multicellular organisms are surprisingly disorderly, reflecting their chaotic evolutionary histories. The genes in these organisms largely consist of a long string of alternating short exons and long introns, as discussed in Chapter 4 (see Figure 4–15D). Moreover, small bits of DNA sequence that code for protein are interspersed with large blocks of seemingly meaningless DNA. Some sections of the genome contain many genes and others lack genes altogether. Proteins that work closely with one another in the cell often have their genes located on different chromosomes, and adjacent genes typically encode proteins that have little to do with each other in the cell. Decoding genomes is therefore no simple matter. Even with the aid of powerful computers, it is difficult for researchers to locate definitively the beginning and end of genes, much less to decipher when and where each gene is expressed in the life of the
Figure 6–1 The pathway from DNA to protein. The flow of genetic information from DNA to RNA (transcription) and from RNA to protein (translation) occurs in all living cells.
human X chromosome: 155 million nucleotide base pairs (~5% of genome) total length of this section = 1.25 million nucleotide pairs
Figure 6–2 Schematic depiction of a small portion of the human X chromosome. As summarized in the key, the known protein-coding genes (starting with Abcd1 and ending with F8) are shown in dark gray, with coding regions (exons) indicated by bars that extend above and below the central line. Noncoding RNAs with known functions are indicated by purple diamonds. Yellow triangles indicate positions within protein-coding regions where the Neanderthal genome sequences codes for a different amino acid than the human genome. The stretch of yellow triangles in the Txtl1 gene appear to have been positively selected for since the divergence of Homo sapiens from Neanderthals some 200,000 years ago. Note that most of the proteins are identical between us and our extinct relative. The blue histogram indicates the extent to which portions of the human genome are conserved with other vertebrate species. It is likely that additional genes, currently unrecognized, also lie within this portion of the human genome.