Metazoans—be they invertebrates such as the fruit fly Drosophila melanogaster and the roundworm Caenorhabditis elegans, or vertebrates such as mice and humans—contain between 13,000 and 23,000 protein-coding genes, about three to four times as many as a yeast (see Table 1-2). Sequencing of entire genomes has shown that many of these genes are conserved among the metazoans, and genetic studies have shown that many of them are essential for the formation and function of specific tissues and organs. Thus many of the organisms listed in Table 1-2 are used to study the roles of these conserved proteins in cell development and function.

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While the human and mouse genomes encode about the same number of proteins as those of the roundworm Caenorhabditis elegans, frogs, and fish, mammalian cells contain about 30 times the DNA of a roundworm and two to three times the DNA of frogs and fish. Only about 10 percent of human DNA encodes proteins. We know now that much of the remaining 90 percent has important functions. Many DNA segments bind proteins that regulate expression of nearby genes, allowing each mammalian gene to make the precise amount of mRNA and protein needed in each of many types of cells.

Other segments of DNA are used to synthesize thousands of RNA molecules whose function in regulating gene expression is only now being uncovered. As an example, hundreds of different micro-RNAs, 20 to 25 nucleotides long, are abundant in metazoan cells, where they bind to and repress the activity of target mRNAs. These small RNAs may indirectly regulate the activity of most or all genes, either by inhibiting the ability of mRNAs to be translated into proteins or by triggering the degradation of target mRNAs (see Chapter 10).

Some of this non-protein-coding DNA probably regulates expression of genes that make us uniquely human. Indeed, fish and humans have about the same number of protein-coding genes—about 20,000—yet as noted above, the human genome is over twice the size of that in fish (see Table 1-2). The human brain can perform complex mental processes such as reading and writing a textbook. Somehow these 20,000 human genes are exquisitely regulated such that humans produce a brain with about 100,000,000,000 neurons, which communicate with one another at about 100,000,000,000,000 interaction sites termed synapses.

Genomics—the study of the entire DNA sequences of organisms—has shown us how close humans really are to our nearest relatives, the great apes (Figure 1-26). Human DNA is 99 percent identical in sequence to that of chimpanzees and bonobos; the 1 percent difference is about 3,000,000 base pairs, but it somehow explains the obvious differences between our species, such as the evolution of human brains during the past 5,000,000 years since we last shared a common ancestor.

Genomics coupled with paleontological findings indicates that humans and mice descended from a common mammalian ancestor that probably lived about 75 million years ago. Nonetheless, both organisms contain about the same number of genes, and about 99 percent of mouse protein-coding genes have homologs in humans, and vice versa. Over 90 percent of mouse and human genomes can be partitioned into regions of synteny—that is, DNA segments that have the same order of unique DNA sequences and genes along a segment of a chromosome. This observation suggests that much of the gene order in the most recent common ancestor of humans and mice has been conserved in both species (Figure 1-27). Of course, mice are not people; relative to humans, mice have expanded families of genes related to immunity, reproduction, and olfaction, probably reflecting the differences between the human and mouse lifestyles.

It’s not only human evolution that interests us! Polar bears live in the Arctic and eat a high-fat diet, mostly composed of seals. Recent genome sequencing allowed researchers to conclude that the most recent common ancestor of polar bears and their brown bear relatives, which live in temperate climates, was present about 500,000 years—or only about 20,000 bear generations—ago. But during that rather short evolutionary period the polar bear genome acquired changes in many genes regulating cardiovascular function, fat metabolism, and heart development, allowing it to consume a diet very rich in fats.