cI cI gene Lysogeny promoter I genes

13.20 Control of Phage X Lysis and Lysogeny Two regulatory proteins, Cro and cl, compete for the operator/promoter sites controlling the transcription of genes for viral lysis and lysogeny. Understanding such transcriptional controls can lead to new ways of controlling viral infections.

Lytic Cycle And Lysogenic Cycle

When the bacterial host is healthy, cl accumulates and activates promoters for integration of phage DNA into the host chromosome. The phage enters the lysogenic cycle.

When the bacterial host is healthy, cl accumulates and activates promoters for integration of phage DNA into the host chromosome. The phage enters the lysogenic cycle.

Prokaryotic Genomes

When DNA sequencing first became possible in the late 1970s, the first biological agents to be sequenced were the simplest viruses. Soon, over 150 viral genomes, including those of important animal and plant pathogens, had been se-quenced. Information on how these virus infect their hosts and reproduce came quickly as a result.

But the manual sequencing techniques used on viruses were not up to the task of elucidating the genomes of prokaryotes and eukaryotes, the smallest of which are a hundred times larger than those of a bacteriophage. In the past decade, however, the automated sequencing techniques described in Chapter 11 have rapidly added many prokaryotic sequences to biologists' store of knowledge.

In 1995, a team led by Craig Venter and Hamilton Smith determined the first sequence of a free-living organism, the bacterium Haemophilus influenzae. Many more prokaryotic sequences have followed. These sequences have revealed not only how prokaryotes apportion their genes to perform different cellular roles, but also how their specialized functions are carried out. A beginning has even been made on the provocative question of what the minimal requirements for a living cell might be.

Three types of information can be obtained from a genomic sequence:

► Open reading frames, which are the coding regions of genes. For protein-coding genes, these regions can be recognized by the start and stop codons for translation.

► Amino acid sequences of proteins. These sequences can be deduced from the DNA sequences of open reading frames by applying the genetic code.

► Gene control sequences, such as promoters and terminators for transcription.

Functional genomics relates gene sequences to functions

Functional genomics is the assignment of roles to the products of genes described by genomic sequencing. This field, less than a decade old, is now a major occupation of biologists.

The only host for the bacterium H. influenzae is humans. It lives in the upper respiratory tract and can cause ear infections or, more seriously, meningitis in children. Its single circular chromosome has 1,830,137 base pairs (Figure 13.21). In addition to its origin of replication and the genes coding for rRNAs and tRNAs, this bacterial chromosome has 1,743 regions containing amino acid codons as well as the transcrip-tional (promoter) and translational (start and stop codons) information needed for protein synthesis—that is, regions that are likely to be genes that code for proteins.

When this sequence was first announced, only 1,007 (58%) of the bacterium's genes had amino acid sequences that corresponded to proteins with known functions—in other words, only 58% were genes that the researchers, based on their knowledge of the functions of bacteria, expected to find. The remaining 42% of its genes coded for proteins that were unknown to researchers. The roles of most of the unknown proteins have been identified since that time, a process known as annotation.

Of the genes and proteins with known roles, most confirmed a century of biochemical description of bacterial enzymatic pathways. For example, genes for enzymes making up entire pathways of glycolysis, fermentation, and electron transport were found. Some of the remaining gene sequences for unknown proteins may code for membrane proteins, including those involved in active transport. Another important finding was that highly infective strains of H. influenzae have genes coding for surface proteins that attach the bacterium to the human respiratory tract, while noninfective strains lack those genes.

Soon after the sequence of H. influenzae was announced, smaller (Mycoplasma genitalium, 580,070 base pairs) and larger (E. coli, 4,639,221 base pairs) prokaryotic sequences were completed. Thus began a new era in biology, the era of comparative genomics, in which the genome sequences of different organisms are compared to see what genes one organism has or is missing, in order to relate the results to physiology.

13.21 Functional Organization of the Genome of H. influenzae

The entire DNA sequence has 1,830,137 base pairs.

13.21 Functional Organization of the Genome of H. influenzae

The entire DNA sequence has 1,830,137 base pairs.

M. genitalium, for example, lacks the enzymes needed to synthesize amino acids, which the other two prokaryotes possess. This finding reveals that M. genitalium is a parasite, which must obtain all its amino acids from its environment, the human urogenital tract. E. coli has 55 regulatory genes coding for transcriptional activators and 58 for repressors; M. genitalium has only 3 genes for activators. Comparisons such as these have led to the formulation of specific questions about how an organism lives the way it does. We'll see many more applications of comparative genomics in the next chapter.

The sequencing of prokaryotic genomes has medical applications

Prokaryotic genome sequencing has important ramifications for the study of organisms that cause human diseases, as the previous section suggests. Indeed, most of the early efforts in sequencing have focused on human pathogens.

► Chlamydia trachomatis causes the most common sexually transmitted disease in the United States. Because it is an intracellular parasite, it has been very hard to study. Among its 900 genes are several for ATP synthesis—something scientists used to think this bacterium could not do.

► Rickettsia prowazekii causes typhus; it infects people bitten by louse vectors. Of its 634 genes, 6 code for proteins that are essential for its virulence. These genes are being used to develop vaccines.

► Mycobacterium tuberculosis causes tuberculosis. It has a large (for a prokaryote) genome, coding for 4,000 proteins. Over 250 of these proteins are used to metabolize lipids, so this may be the main way that the bacterium gets its energy. Some of its genes code for previously unidentified cell surface proteins; these genes are targets for potential vaccines.

► Streptomyces coelicolor and its close relatives produce two-thirds of all the antibiotics currently in clinical use, including streptomycin, tetracycline, and erythromycin. The genome sequence of this bacterium reveals that there are 22 clusters of genes responsible for antibiotic production, of which only 4 were previously known. This finding may lead to more and better antibiotics to combat resistant pathogens.

► E. coli strain O157:H7 in hamburger can cause severe illness when ingested, as happens to at least 70,000 people a year in the

United States. Its genome has 5,416 genes, of which 1,387 are different from those in the familiar (and harmless) laboratory strains of this bacterium. Remarkably, many of these unique genes are also present in other pathogenic species, such as Salmonella and Shigella. This finding suggests that there is extensive genetic exchange between these species, and that "superbugs" are on the horizon.

What genes are required for cellular life?

When the genomes of prokaryotes and eukaryotes are compared, a striking conclusion arises: There are some universal genes that are present in all organisms. There are also some universal gene segments—coding for an ATP binding site, for example—that are present in many genes in many organisms. These findings suggest that there is some ancient, minimal set of DNA sequences that all cells must have. One way to identify these sequences is to look for them (or, more realistically, to have a computer look for them).

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