Ch 10. Molecular Structure of Chromosomes and Transposable Elements PDF

CHAPTER OUTLINE 10.1 Organization of Functional Sites Along Bacterial Chromosomes 10.2 Structure of Bacterial Chromosomes 10.3 Organization of Functional Sites Along Eukaryotic Chromosomes 10.4 Sizes of Eukaryotic Genomes and Repeti...

CHAPTER OUTLINE 10.1 Organization of Functional Sites Along Bacterial Chromosomes 10.2 Structure of Bacterial Chromosomes 10.3 Organization of Functional Sites Along Eukaryotic Chromosomes 10.4 Sizes of Eukaryotic Genomes and Repetitive Sequences 10.5 Transposition 10.6 Structure of Eukaryotic 0.8 μm Chromosomes in Nondividing Cells 10 10.7 Structure of Eukaryotic Structure of a bacterial chromosome. Electron micrograph of a Chromosomes During Cell Division bacterial chromosome, which has been released from a bacterial cell. ©Dr. Gopal Murti/Science Source MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS Chromosomes are the structures within living cells that contain In this chapter, we will examine three features of bacterial the genetic material. The term genome refers to the entire comple- and eukaryotic chromosomes. First, we will consider the general ment of genetic material in an organism or species. For bacteria, organization of functional sites along a chromosome. Second, we the genome is typically a single circular chromosome. For eukary- will explore a process called transposition, in which short seg- otes, genetic material is found in different cellular compartments. ments of DNA, called transposable elements (TEs), are able to The nuclear genome in humans includes 22 autosomes, the X move to multiple sites within chromosomes and accumulate in chromosome, and (in males) the Y chromosome. Eukaryotes also large numbers. Finally, we will examine the molecular mecha- have a mitochondrial genome, and plants have a chloroplast nisms that make chromosomes more compact. genome. The primary function of the genetic material is to store the information needed to produce the characteristics of an organism. 10.1 ORGANIZATION OF As we saw in Chapter 9, the sequence of bases in a DNA molecule FUNCTIONAL SITES ALONG stores information. To fulfill their role at the molecular level, chro- BACTERIAL CHROMOSOMES mosomal sequences facilitate four important processes: Learning Outcome: ∙ the synthesis of RNA and cellular proteins; 1. Describe the organization of functional sites along bacterial ∙ the replication of chromosomes; chromosomes. ∙ the proper segregation of chromosomes; and ∙ the compaction of chromosomes so that they fit within liv- Figure 10.1 shows the general features of a bacterial chromo- ing cells. some. In most species, the chromosomal DNA is a circular 230  10.2 STRUCTURE OF BACTERIAL CHROMOSOMES 231 F I G U R E 10. 1 Organization of sequences in bacterial chromo- Key features: somal DNA. Most, but not all, bacterial species CONCEPT CHECK: What types of contain circular chromosomal DNA. Origin of sequences constitute most of a replication bacterial genome? Most bacterial species contain a single type of chromosome, but it may be present in multiple copies. A typical chromosome is a few million base pairs in length. Several thousand different genes are interspersed throughout the chromosome. The short regions between adjacent genes are called intergenic regions. One origin of replication is required to initiate DNA replication. Genes Intergenic regions Repetitive sequences may be interspersed throughout the chromosome. Repetitive sequences molecule, though some bacterial species have linear chromo- somes (Figure 10.1). Although bacteria usually contain a single 10.2 STRUCTURE OF BACTERIAL type of chromosome, more than one copy of that chromosome CHROMOSOMES may be found within one bacterial cell. A typical bacterial chro- mosome is a few million base pairs (bp) in length. For example, Learning Outcomes: the chromosome of Escherichia coli has approximately 4.6 mil- 1. Outline the processes that make a bacterial chromosome lion bp, and that of Haemophilus influenzae has roughly 1.8 mil- more compact. lion bp. A bacterial chromosome commonly has a few thousand 2. Describe how DNA gyrase causes DNA supercoiling. different genes, which are interspersed throughout the entire chromosome. Protein-encoding genes (also called structural Inside a bacterial cell, a chromosome is highly compacted and genes) account for the majority of bacterial DNA. The nontran- found within a region of the cell known as a nucleoid. Depending scribed regions of DNA located between adjacent genes are on the growth conditions and phase of the cell cycle, bacteria may termed intergenic regions. have one to four identical chromosomes per cell. In addition, the Other sequences in chromosomal DNA influence DNA rep- number of copies varies depending on the bacterial species. As lication, gene transcription, and chromosome structure. For shown in Figure 10.2, each chromosome is found within its own example, bacterial chromosomes have one origin of replication distinct nucleoid in the cell. Unlike the eukaryotic nucleus, the (see Figure 10.1), a sequence that is a few hundred base pairs in bacterial nucleoid is not a separate cellular compartment sur- length. This nucleotide sequence functions as an initiation site for rounded by a membrane. Rather, the DNA in a nucleoid is in direct the assembly of several proteins required for DNA replication. contact with the cytoplasm of the cell. In this section, we will Also, a variety of repetitive sequences have been identified in explore the structure of bacterial chromosomes and the processes many bacterial species. These sequences are found in multiple by which they are compacted to fit within a nucleoid. copies and are usually interspersed within the intergenic regions throughout the bacterial chromosome. Repetitive sequences may The Formation of Chromosomal Loops Helps play a role in a variety of genetic processes, including DNA fold- ing, DNA replication, gene regulation, and genetic recombination. Make the Bacterial Chromosome More Compact As discussed in Section 10.5, some repetitive sequences are trans- To fit within the bacterial cell, the chromosomal DNA must be posable elements that can move throughout the genome. compacted about 1000-fold. The mechanism of bacterial chromo- some compaction is not entirely understood, and it may vary among different bacterial species. Figure 10.3 shows a schematic 10.1 COMPREHENSION QUESTION drawing of a chromosome that has been removed from an E. coli cell. As the drawing shows, the chromosome has a central core 1. A bacterial chromosome typically contains with many loops emanating from the core. a. a few thousand genes. ∙ The loops that emanate from the core, which are called b. one origin of replication. microdomains, are typically 10,000 base pairs (10 kbp) in c. some repetitive sequences. length. An E. coli chromosome is expected to have about d. all of the above. 400 to 500 microdomains. The lengths and boundaries of 232 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS these microdomains are thought to be dynamic, changing 0.3 μm in response to environmental conditions. ∙ In E. coli, many adjacent microdomains are further orga- nized into macrodomains that are about 800 to 1000 kbp in length; each macrodomain contains about 80 to 100 micro- domains. The macrodomains are not evident in Figure 10.3. To form microdomains and macrodomains, bacteria use a set of DNA-binding proteins called nucleoid-associated proteins (NAPs) that facilitate chromosome compaction and organization. These proteins either bend the DNA or act as bridges that cause different regions of DNA to bind to each other. NAPs also facili- tate chromosome segregation and play a role in gene regulation. Examples of NAPs include histone-like nucleoid structuring (H- NS) proteins and structural maintenance of chromosomes (SMC) proteins. SMCs are also found in eukaryotes, and later in this F I G U RE 10.2 The localization of nucleoids within the bacte- chapter, we will examine how they tether segments of DNA to rium Bacillus subtilis. The nucleoids are fluorescently labeled, so they each other (look ahead to Figure 10.26). appear as bright blue regions within the bacterial cytoplasm. Note that two or more nucleoids may be found within a cell. ©M. Wurtz/Biozentrum, University of Basel/Science Source GENETIC TIPS THE QUESTION: As noted in Chapter 9, CONCEPT CHECK: How many nucleoids are in this bacterial cell? 1 bp of DNA is approximately 0.34 nm in length. A bacterial chromosome is about 4 million bp in length. The dimensions of the cytoplasm of a bacterium, such as E. coli, are roughly 0.5 μm wide and 1.0 μm long. A. A microdomain is a loop of DNA that contains about 10,000 bp. If it was stretched out linearly, how long (in micrometers) would a microdomain be? B. If a bacterial microdomain was circular, what would be its diameter? (Note: Circumference = πD, where D is the diameter of the circle.) C. Is the diameter of the circular microdomain calculated in part B small enough to fit inside a bacterium? T OPIC: What topic in genetics does this question address? The topic is the dimensions of a bacterial chromosome. More specifically, the question asks you to calculate the dimensions of a microdomain. I NFORMATION: What information do you know based on the question and your understanding of the topic? In the question, you are reminded that the length of 1 bp of DNA is about 0.34 nm and that a bacterial chromosome is about 4 million bp in length. One microdomain is a loop with about 10,000 bp. You are also told that the bacterial cytoplasm is about 0.5 μm wide and 1.0 μm long and given the equation for calculating the circumference of a circle. P ROBLEM-SOLVING S TRATEGY: Make a calculation. Compare and contrast. For part A, you simply multiply 10,000 by 0.34 nm, which is the length of 1 bp. For part B, you use the equation that is given. The circumference is the linear length of F I G U RE 10.3 Core and microdomains of a bacterial chromo- the DNA. For part C, you compare the answer to part B to the some. This is a schematic drawing of an E. coli chromosome that has dimensions of the bacterial cytoplasm. been extracted from a cell and viewed by electron microscopy. The core is in the center with many loops (microdomains) emanating from it. Not all bacterial species have their chromosomes organized into ANSWER: microdomains and macrodomains. A. One microdomain is 10,000 bp. One base pair is 0.34 nm, which Source: Wang, Xindan, Llopis, Paula Montero, and Rudner, David Z., “Organization and equals 0.00034 μm. You multiply these two numbers: Segregation of Bacterial Chromosomes,” Nature Reviews Genetics, vol. 14, no. 3, March, 2013, 191–203. (10,000) (0.00034 μm) = 3.4 μm  10.2 STRUCTURE OF BACTERIAL CHROMOSOMES 233 B. Circumference = πD twisting motion, and overwinding is a right-handed twisting mo- 3.4 μm = πD tion. Along the left side of Figure 10.4, one of the plates has been D = 1.1 μm given a left-handed twist that tends to unwind the helix. As the C. The diameter is a little too big to fit inside a bacterium such as helix absorbs this force, the underwinding motion can cause: E. coli. NAPs and supercoiling make the microdomains much ∙ fewer turns (Figure 10.4b); more compact so that a single chromosome can occupy a nucleoid ∙ the formation of a negative supercoil (Figure 10.4c). within the bacterial cell. On the right side of Figure 10.4, one of the plates has been given a right-handed twist, which overwinds the double helix. Over- winding can cause: DNA Supercoiling Further Compacts the ∙ more turns (Figure 10.4d); Bacterial Chromosome ∙ the formation of a positive supercoil (Figure 10.4e). Because DNA is a long thin molecule, twisting forces can dra- matically change its conformation. This effect is similar to what The DNA conformations shown in Figure 10.4a, c, and e differ happens when you twist a rubber band. If twisted in one direction, only with regard to supercoiling. These three DNA conformations a rubber band eventually coils itself into a compact structure as it are referred to as topoisomers of each other. The DNA conforma- absorbs the energy applied by the twisting motion. Because the tions shown in Figure 10.4b and d are not structurally stable and two strands within DNA already coil around each other, the for- do not occur in living cells. mation of additional coils due to twisting forces is referred to as Chromosome Function Is Influenced DNA supercoiling. The DNA within microdomains is further compacted because of DNA supercoiling. by DNA Supercoiling How do twisting forces affect DNA structure? Figure 10.4 The chromosomal DNA in living bacteria is negatively super- illustrates four possibilities. In Figure 10.4a, a double-stranded coiled. In the chromosome of E. coli, about one negative supercoil DNA molecule with five complete turns is anchored between two occurs per 40 turns of the double helix. Negative supercoiling has plates. In this hypothetical example, the ends of the DNA molecule important consequences. As already mentioned, the supercoiling cannot rotate freely. Both underwinding and overwinding of the of chromosomal DNA makes it much more compact. Therefore, DNA double helix can cause supercoiling of the helix. Because B supercoiling helps to greatly decrease the size of the bacterial DNA is a right-handed helix, underwinding is a left-handed chromosome. In addition, negative supercoiling also affects DNA F I GU R E 1 0. 4 Schematic representation of DNA supercoiling. In this example, the DNA in (a) is 1 anchored between two plates and given a twist as noted 2 by the arrows. A left-handed twist (underwinding) can 10 bp 3 produce either (b) fewer turns or (c) a negative supercoil. per turn A right-handed twist (overwinding) can produce (d) more 4 turns or (e) a positive supercoil. The structures shown in 5 (b) and (d) are unstable. (a) No supercoil 360° left-handed 360° right-handed twist (underwinding) twist (overwinding) or or 1 1 2 12.5 bp 10 bp 8.3 bp 2 10 bp 1 1 per turn 2 per turn per turn 3 per turn 3 (not a plus 1 (not a plus 1 2 4 4 stable 3 negative 3 stable positive structure) supercoil 5 structure) 5 supercoil 5 4 4 6 (b) Unstable (c) Negative supercoil (d) Unstable (e) Positive supercoil 234 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS Area of most of the chromosomal DNA is negatively supercoiled and negative supercoiling compact, the force of negative supercoiling may promote DNA strand separation in small regions. This enhances genetic activities Strand such as replication and transcription that require the DNA strands separation to be separated. How does bacterial DNA become supercoiled? In 1976, Martin Gellert and colleagues discovered the enzyme DNA gyrase, also known as topoisomerase II. This enzyme, which contains four subunits (two A and two B subunits), introduces negative super- Circular coils (or relaxes positive supercoils) using energy from ATP (Fig- chromosome ure 10.6a). To alter supercoiling, DNA gyrase has two sets of jaws that allow it to grab onto two regions of DNA. One of the DNA F I G U RE 10.5 Negative supercoiling promotes strand regions is grabbed by the lower jaws and then is wrapped in a right- separation. handed direction around the two A subunits. The upper jaws then CONCEPT CHECK: Why is strand separation beneficial? clamp onto another region of DNA. The DNA in the lower jaws is cut in both strands, and the other region of DNA is then released from the upper jaws and passed through this double-stranded break. function. To understand how it does so, remember that negative To complete the process, the double-stranded break is ligated back supercoiling is due to an underwinding force on the DNA. There- together. The net result is that two negative supercoils have been fore, negative supercoiling creates tension on the DNA strands introduced into the DNA molecule (Figure 10.6b). In addition, that may be released by their separation (Figure 10.5). Although DNA gyrase can untangle DNA molecules. For example, as Upper jaws DNA wraps around DNA binds to the A subunits in a Upper jaws the lower jaws. right-handed direction. clamp onto DNA. DNA held in lower jaws is cut. DNA held in upper Lower jaws DNA jaws is released and passes downward through the opening A subunits B subunits in the cut DNA. This process uses 2 ATP molecules. (a) Molecular mechanism of DNA gyrase function Circular Cut DNA is ligated back DNA 2 negative together and the DNA is molecule DNA gyrase supercoils released from DNA gyrase. 2 ATP (b) Overview of DNA gyrase function FI GU RE 10. 6 The action of DNA gyrase. (a) DNA gyrase, also known as topoisomerase II, is composed of two A and two B subunits. The lower jaws and then the upper jaws bind to two regions of DNA. The lower region is wrapped around the A subunits, which then cleave this DNA. The unbroken segment of DNA is released from the upper jaws and passes through the break. The break is re- paired. The B subunits capture the energy from the hydrolysis of two ATP molecules to catalyze this process. (b) The result is that two negative turns have been introduced into the DNA molecule. CONCEPT CHECK: In your own words, describe the step that requires the use of ATP.  10.3 ORGANIZATION OF FUNCTIONAL SITES ALONG EUKARYOTIC CHROMOSOMES 235 discussed in Chapter 11, circular DNA molecules are sometimes Eukaryotic species have one or more sets of chromosomes in the intertwined following DNA replication (see Figure 11.14). Such cell nucleus; each set is composed of several different linear chro- interlocked molecules can be separated by DNA gyrase. mosomes (refer back to Figure 8.1). Humans, for example, have A second type of enzyme, topoisomerase I, relaxes nega- two sets of 23 chromosomes each, for a total of 46. Each eukary- tive supercoils. This enzyme can bind to a negatively supercoiled otic chromosome contains a long, linear DNA molecule that is region and introduce a break in one of the DNA strands. After one typically tens of millions to hundreds of millions of base pairs in DNA strand has been broken, the DNA molecule rotates to relieve length (Figure 10.7). the tension that is caused by negative supercoiling. This rotation A single chromosome usually has a few hundred to several relaxes negative supercoiling. The broken strand is then repaired. thousand different genes. A typical eukaryotic gene is several The competing actions of DNA gyrase and topoisomerase I gov- thousand to tens of thousands of base pairs in length. In less com- ern the overall supercoiling of the bacterial DNA. plex eukaryotes such as yeast, genes are relatively small, often The ability of DNA gyrase to introduce negative supercoils several hundred to a few thousand base pairs long. In more com- into DNA is critical for bacterial survival. For this reason, much re- plex eukaryotes such as mammals and flowering plants, search has been aimed at identifying drugs that specifically block this enzyme’s function as a way to cure or alleviate diseases caused by bacteria. Two main classes—quinolones and coumarins—inhibit gyrase and other bacterial topoisomerases, thereby blocking bacte- Key features: rial cell growth. These drugs do not inhibit eukaryotic topoisomer- Telomere ases, which are structurally different from their bacterial counterparts. Eukaryotic chromosomes are usually linear. This finding has been the basis for the production of many drugs Eukaryotic chromosomes occur in sets. with important antibacterial applications. An example is ciprofloxa- Many species are diploid, which means that cin (known also by the brand name Cipro), which is used to treat a Origin of somatic cells contain 2 sets of chromosomes. wide spectrum of bacterial diseases, including anthrax. replication A typical chromosome is tens of millions to hundreds of millions of base pairs in length. 10.2 COMPREHENSION QUESTIONS Genes are interspersed throughout the chromosome. A typical chromosome contains between a few hundred and several 1. Mechanisms that make the bacterial chromosome more com- Origin of thousand different genes. pact include replication a. the formation of microdomains and macrodomains. Each chromosome contains many origins of replication that are interspersed about every Kinetochore b. DNA supercoiling. proteins 100,000 base pairs. c. crossing over. Centromere Each chromosome contains a centromere d. both a and b. that forms a recognition site for the kinetochore proteins. 2. Negative supercoiling can enhance transcription and DNA repli- cation because it Telomeres contain specialized sequences a. allows the binding of proteins in the major groove. located at both ends of the linear chromosome. b. promotes DNA strand separation. Origin of replication c. makes the DNA more compact. Repetitive sequences are commonly found near centromeric and telomeric regions, but d. causes all of the above. they may also be interspersed throughout the chromosome. 3. DNA gyrase a. promotes negative supercoiling. b. relaxes positive supercoils. Origin of c. cuts DNA strands as part of its function. replication d. does all of the above. 10.3 ORGANIZATION OF FUNCTIONAL SITES ALONG Telomere Genes EUKARYOTIC CHROMOSOMES Repetitive sequences Learning Outcome: F IG U RE 1 0. 7 Organization of eukaryotic chromosomes. 1. Describe the organization of functional sites along a eukary- CONCEPT CHECK: What are some differences between the types of otic chromosome. sequences found in eukaryotic chromosomes versus those in bacterial chromosomes? 236 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS protein-encoding genes tend to be much longer due to the presence of introns—noncoding intervening sequences. As described in 10.3 COMPREHENSION QUESTION Chapter 12, exons are regions of an RNA molecule that remain 1. The chromosomes of eukaryotes typically contain after splicing has removed the introns. The size of introns ranges a. a few hundred to several thousand different genes. from less than 100 bp to more than 10,000 bp. Therefore, the b. multiple origins of replication. presence of large introns can greatly increase the lengths of eukaryotic genes. c. a centromere. In addition to genes, chromosomes contain three types of d. telomeres at their ends. regions that are required for chromosomal replication and segrega- e. all of the above. tion: origins of replication, centromeres, and telomeres. As men- tioned previously, origins of replication are chromosomal sites that are necessary to initiate DNA replication. Unlike most bacte- 10.4 SIZES OF EUKARYOTIC rial chromosomes, which contain only one origin of replication, eukaryotic chromosomes contain many origins, interspersed ap- GENOMES AND REPETITIVE proximately every 100,000 bp. The function of origins of replica- SEQUENCES tion is discussed in greater detail in Chapter 11. Centromeres are regions that play a role in the proper seg- Learning Outcomes: regation of chromosomes during mitosis and meiosis. In most eu- 1. Describe the variation in size of eukaryotic genomes. karyotic species, each chromosome contains a single centromere, 2. Define repetitive sequence, and explain how this type of se- which usually appears as a constricted region of a mitotic chromo- quence affects genome sizes. some. A centromere functions as a site for the formation of a ki- netochore, which assembles just before and during the very early stages of mitosis and meiosis. The kinetochore is composed of a The total amount of DNA in cells of eukaryotic species is usually group of proteins that link the centromere to the spindle apparatus much greater than the amount in bacterial cells. In addition, eu- during mitosis and meiosis, ensuring the proper segregation of the karyotic genomes contain many more genes than their bacterial chromosomes to each daughter cell. counterparts. In this section, we will examine the sizes of eukary- In certain yeast species, such as Saccharomyces cerevisiae, otic genomes and consider how repetitive sequences may have a the centromere has a defined DNA sequence that is about 125 bp significant effect on those sizes. in length. This type of centromere is called a point centromere. By comparison, the centromeres found in more complex eukary- The Sizes of Eukaryotic Genomes Vary Substantially otes are much larger and contain tandem arrays of short repetitive Different eukaryotic species vary dramatically in the size of their DNA sequences. (Tandem arrays are described in Section 10.4.) genomes (Figure 10.8a; note that the graph uses a log scale). In These are called regional centromeres. They can range in length many cases, this variation is not related to the complexity of the from several thousand to more than a million base pairs. The species. For example, two closely related species of salamander, repeated DNA sequences within regional centromeres by them- Plethodon richmondi and Plethodon larselli, differ considerably in selves are not necessary or sufficient to form a functional centro- genome size (Figure 10.8b, c). The genome of P. larselli is more mere with a kinetochore. Other features must be present in a than twice as large as the genome of P. richmondi. However, the functional centromere. For example, a distinctive feature of all genome of P. larselli probably doesn’t contain more genes. How eukaryotic centromeres is that histone protein H3 is replaced with do we explain the difference in genome size? The additional DNA a histone variant called CENP-A. (Histone variants are described in P. larselli is due to the accumulation of many copies of repeti- in Chapter 15.) However, researchers are still trying to identify all tive DNA sequences. In some species, the amounts of these re- of the biochemical properties that distinguish regional centro- petitive sequences have reached enormous levels. Such repetitive meres and understand how these properties are transmitted dur- sequences do not encode proteins, and their function remains a ing cell division. matter of controversy and great interest. The structure and signifi- The ends of linear eukaryotic chromosomes have special- cance of repetitive DNA will be discussed next. ized regions known as telomeres. Telomeres serve several impor- tant functions in the replication and stability of the chromosome. The Genomes of Eukaryotes Contain Sequences As discussed in Chapter 8, telomeres prevent chromosomal rear- That Are Unique, Moderately Repetitive, rangements such as translocations. In addition, they prevent chro- mosome shortening in two ways. First, the telomeres protect or Highly Repetitive chromosomes from digestion via enzymes called exonucleases The term sequence complexity refers to the number of times a that recognize the ends of DNA. Second, an unusual form of DNA particular base sequence appears throughout the genome of a spe- replication occurs at the telomere to ensure that eukaryotic chro- cies. Unique, or nonrepetitive, sequences are those found once or mosomes do not become shortened with each round of DNA rep- a few times within a genome. Protein-encoding genes are typically lication (see Chapter 11). unique sequences of DNA. The vast majority of proteins in  10.4 SIZES OF EUKARYOTIC GENOMES AND REPETITIVE SEQUENCES 237 Fungi Vascular plants Insects Mollusks Fishes (b) Plethodon richmondi Salamanders Amphibians Reptiles Birds Mammals 106 107 108 109 1010 1011 1012 (a) Genome sizes (nucleotide base pairs per haploid genome) (c) Plethodon Iarselli F I G U R E 10. 8 Haploid genome sizes among groups of eukaryotic species. (a) Ranges of genome sizes among different groups of eukary- otes. (b) A species of salamander, Plethodon richmondi, and (c) a close relative, Plethodon larselli. The genome of P. larselli is over twice as large as that of P. richmondi. Genes→Traits The two species of salamander shown here have very similar traits, even though the genome of P. larselli is over twice as large as that of P. richmondi. However, the genome of P. larselli is not likely to contain twice as many genes. Rather, the additional DNA is due to the accumulation of short repetitive DNA sequences that do not contain functional genes and are present in many copies. (a): Source: Gregory, T. Ryan, “Eukaryotic Genome Size Databases,” Nucleic Acids Research, vol. 35, January, 2007, D332–D338.; (b): ©Ann & Rob Simpson; (c): ©Gary Nafis CONCEPT CHECK: What are two reasons for the wide variation in genome sizes among eukaryotic species? eukaryotic cells are encoded by genes present in one or a few cop- Moderately repetitive sequences are found a few hundred ies. In the case of humans, unique sequences make up roughly to several thousand times in a genome. In a few cases, moderately 41% of the entire genome (Figure 10.9). These unique sequences repetitive sequences are multiple copies of the same gene. For include the protein-encoding regions of genes (2%), introns (24%), example, the genes that encode ribosomal RNA (rRNA) are found and unique regions that are not found within genes (15%). in many copies. Ribosomal RNA is necessary for the functioning of ribosomes. Cells need a large amount of rRNA for making ribo- somes, and producing such an amount is facilitated by having mul- 100 tiple copies of the genes that encode rRNA. Likewise, the genes Percentage in the human genome encoding histone proteins are also found in multiple copies because 80 a large number of histone proteins are needed for the structure of chromosomes. In addition, other types of functionally important 59% sequences are moderately repetitive. For example, moderately re- 60 Unique sequences petitive sequences may play a role in the regulation of gene tran- 40 scription and translation. By comparison, some moderately 24% repetitive sequences do not play a functional role and are derived 20 15% from transposable elements (TEs)—short segments of DNA that have the ability to move within a genome. This category of repeti- 2% 0 tive sequences is discussed in greater detail in Section 10.5. Regions of Introns and Unique Repetitive Highly repetitive sequences are found tens of thousands or genes that other parts sequences DNA encode of genes not found even millions of times throughout a genome. Each copy of a highly proteins such as within genes repetitive sequence is relatively short, ranging from a few nucleotides (exons) enhancers to several hundred in length. A widely studied example is the Alu fam- Classes of DNA sequences ily of sequences found in humans and other primates. The Alu se- quence is approximately 300 bp long. This sequence derives its name F I G U R E 10. 9 Relative amounts of unique and repetitive from the observation that it contains a site for cleavage by a restriction DNA sequences in the human genome. enzyme known as AluI. (The function of restriction enzymes is 238 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS described in Chapter 20.) The Alu sequence represents about 10% of As we have seen, sizeable portions of many species’ genomes are the total human DNA and occurs approximately every 5000–6000 composed of repetitive sequences. In many cases, the repetitive bp! Evolutionary studies suggest that the Alu sequence arose 65 mya sequences are due to transposition, which is a process in which a from a section of a single ancestral gene known as the 7SL RNA gene. short segment of DNA is inserted into a new location in the ge- Since that time, this gene has become a type of TE called a retrotrans- nome. The DNA segments that transpose themselves are known as poson, which is transcribed into RNA, copied into DNA, and inserted transposable elements (TEs). TEs have sometimes been referred to into the genome (see Section 10.5). Over the past 65 million years, the as “jumping genes” because they are inherently mobile. Alu sequence has been copied and inserted into the human genome Transposable elements were first identified by Barbara Mc- many times and is now present in about 1,000,000 copies. Clintock in the early 1950s during her classic studies with corn plants. Repetitive sequences, like the Alu family, are interspersed Since that time, geneticists have discovered many different types of throughout the genome. However, some moderately and highly re- TEs in organisms as diverse as bacteria, fungi, plants, and animals. petitive sequences are clustered together in a tandem array, also The advent of molecular technology has allowed scientists to better known as a tandem repeat. In a tandem array, a very short nucleo- understand the characteristics of TEs that enable them to be mobile. tide sequence is repeated many times in a row. In Drosophila, for In this section, we will examine the characteristics of TEs and explore example, 19% of the chromosomal DNA consists of highly repeti- the mechanisms by which they move. We will also discuss the biolog- tive sequences found in tandem arrays. An example is shown here. ical significance of TEs. 𝙰𝙰𝚃𝙰𝚃𝙰𝙰𝚃𝙰𝚃𝙰𝙰𝚃𝙰𝚃𝙰𝙰𝚃𝙰𝚃𝙰𝙰𝚃𝙰𝚃𝙰𝚃𝙰𝙰𝚃𝙰𝚃 𝚃𝚃𝙰𝚃𝙰𝚃𝚃𝙰𝚃𝙰𝚃𝚃𝙰𝚃𝙰𝚃𝚃𝙰𝚃𝙰𝚃𝚃𝙰𝚃𝙰𝚃𝙰𝚃𝚃𝙰𝚃𝙰 McClintock Found That Chromosomes of Corn In this particular tandem array, two related sequences, AATAT Plants Contain Loci That Can Move and AATATAT, are repeated. As mentioned earlier, tandem arrays McClintock began her scientific career as a student at Cornell of short sequences are commonly found in centromeric regions of University. Her interests quickly became focused on the structure chromosomes and can be quite long, sometimes more than and function of the chromosomes of corn plants, an interest that 1,000,000 bp in length! continued for the rest of her life. She spent countless hours exam- What is the functional significance of highly repetitive se- ining corn chromosomes under the microscope. She was techni- quences? Whether they have any significant function is controver- cally gifted and had a theoretical mind that could propose ideas sial. Some experiments in Drosophila indicate that highly that conflicted with conventional wisdom. repetitive sequences may be important in the proper segregation of During her long career as a scientist, McClintock identified chromosomes during meiosis. It is not yet clear if highly repetitive many unusual features of corn chromosomes. In one of her corn DNA plays the same role in other species. The sequences within strains, she noticed that a particular site in chromosome 9 had the highly repetitive DNA vary greatly from species to species. Like- strange characteristic of showing a fairly high rate of breakage. wise, the amount of highly repetitive DNA can vary a great deal McClintock termed this a mutable site, or mutable locus. The even among closely related species (as noted in Figure 10.8). mutable locus was named Ds (for dissociation), because chromo- somal breakage occurred frequently there. McClintock identified strains of corn in which the Ds locus was 10.4 COMPREHENSION QUESTION found in different places within the corn genome. In one case, she determined that Ds was located in the middle of a gene affecting ker- 1. Which of the following are moderately repetitive sequences? nel color. The C allele provides dark red color, whereas c is a recessive a. Genes that encode rRNA allele of the same gene and causes a colorless kernel. The endosperm b. Most protein-encoding genes of corn kernels is triploid. The drawing below shows the genotype of chromosome 9 in the endosperm of one of McClintock’s strains. c. Both a and b CDsC d. None of the above c 10.5 TRANSPOSITION c Learning Outcomes: 1. Summarize the studies of McClintock, and explain how they This strain had an interesting phenotype. Most of the corn kernel was revealed the existence of transposable elements. colorless, but it also contained some red sectors. How did McClintock 2. Describe the organization of sequences within different explain this phenotype? She proposed the following: types of transposable elements. 3. Explain how transposons and retrotransposons move to new 1. The colorless background of a kernel was due to the transposi- locations in a genome. tion of Ds into the C allele, which would inactivate that allele. 4. Discuss the effects of transposable elements on gene function. 2. In a few cells, Ds occasionally transposed out of the C al- lele during kernel growth (see drawing below). During  10.5 TRANSPOSITION 239 transposition, Ds moved out of the C allele to a new loca- tion, and the two parts of the C allele were rejoined, thereby restoring its function. As the kernel grew, such a cell would continue to divide, resulting in a red sector. Ds has transposed out of C gene to a new chromosomal location. Transposon C c Transposon c (a) Simple transposition On rare occasions, when McClintock crossed a strain carrying Ds in the middle of the C allele to a strain carrying the recessive c allele, the cross produced a kernel that was completely red. In this case, Ds had transposed out of the C allele prior to kernel growth, prob- ably during gamete formation. In offspring that grew from a solid Retrotransposon red kernel, McClintock determined that the Ds locus had moved out Transcription of the C allele to a new location. In addition, the restored C allele DNA behaved normally. In other words, the C allele was no longer highly RNA Reverse mutable; the kernels did not show a sectoring phenotype. Taken to- transcriptase gether, the results were consistent with the hypothesis that the Ds locus can move around the corn genome by transposition. When McClintock published these results in 1951, they were met with great skepticism. Some geneticists of that time were una- ble to accept the idea that the genetic material was susceptible to frequent rearrangement. Instead, they believed that the genetic ma- terial was very stable and permanent in its structure. Over the next Retrotransposon Retrotransposon several decades, however, the scientific community came to realize that TEs are a widespread phenomenon. Much like Gregor Mendel and Charles Darwin, Barbara McClintock was clearly ahead of her (b) Retrotransposition time. She was awarded the Nobel Prize in physiology or medicine in 1983, more than 30 years after her original discovery. F IG U RE 1 0. 1 0 Different mechanisms of transposition. CONCEPT CHECK: Which of these mechanisms causes the TE to increase in Transposable Elements Move by Different number? Transposition Pathways Since McClintock’s pioneering studies, many different TEs have been found in bacteria, fungi, plants, and animals. Different types Each Type of Transposable Element Has a of transposition mechanisms have been identified. In simple Characteristic Pattern of DNA Sequences transposition, the TE is removed from its original site and trans- Research on TEs from many species has established that the DNA ferred to a new target site (Figure 10.10a). This mechanism is sequences within them are organized in several different ways. called a cut-and-paste mechanism because the element is cut out Figure 10.11 presents a few of those ways, although many varia- of its original site and pasted into a new one. Transposable ele- tions are possible. All TEs are flanked by direct repeats (DRs), ments that move via simple transposition are widely found in bac- also called target-site duplications, which are identical base terial and eukaryotic species. Such TEs are also called transposons. sequences that are oriented in the same direction and repeated. Another type of transposable element moves via an RNA in- Direct repeats are adjacent to both ends of any TE. The simplest termediate. This form of transposition, termed retrotransposition, TE is known as an insertion element (IS element). As shown in is found only in eukaryotic species, where it is very common Figure 10.11a, an IS element has two important characteristics. (Figure 10.10b). Transposable elements that move via retrotranspo- First, both ends of the element contain inverted repeats (IRs). sition are known as retrotransposons, or retroelements. In retro- Inverted repeats are DNA sequences that are identical (or very transposition, the element is transcribed into RNA. An enzyme similar) but run in opposite directions, such as the following: called reverse transcriptase uses the RNA as a template to synthesize a DNA molecule that is integrated into a new region of the genome. 𝟻′−𝙲𝚃𝙶𝙰𝙲𝚃𝙲𝚃𝚃−𝟹′ 𝚊𝚗𝚍 𝟻′−𝙰𝙰𝙶𝙰𝙶𝚃𝙲𝙰𝙶−𝟹′ Retrotransposons increase in number during retrotransposition. 𝟹′−𝙶𝙰𝙲𝚃𝙶𝙰𝙶𝙰𝙰−𝟻′ 𝟹′−𝚃𝚃𝙲𝚃𝙲𝙰𝙶𝚃𝙲−𝟻′ 240 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS proteins, such as reverse transcriptase and integrase, that are needed for the retrotransposition process. By comparison, non-LTR retrotransposons do not resem- DR IR Transposase IR DR gene ble retroviruses in having LTRs. They may contain a gene that Insertion element encodes a protein that functions as both a reverse transcriptase and an endonuclease (see Figure 10.11b). As discussed later, these functions are needed for retrotransposition. Some non-LTR retro- transposons are evolutionarily derived from normal eukaryotic DR IR Transposase Antibiotic- IR DR genes. For example, the Alu family of repetitive sequences found gene resistance in humans is derived from a single ancestral gene known as the Simple transposon gene 7SL RNA gene (that encodes a component of the complex called signal recognition particle, which targets newly made proteins to (a) Elements that move by simple transposition the endoplasmic reticulum). This gene sequence has been copied by retrotransposition many times, and the current number of cop- ies in the human genome is approximately 1 million. Transposable elements are considered to be complete, or DR LTR Reverse Integrase LTR DR autonomous elements, when they contain all of the information nec- transcriptase gene essary for transposition or retrotransposition to take place. However, gene TEs are often incomplete, or nonautonomous. A nonautonomous LTR retrotransposon element typically lacks a gene such as one that encodes transposase or reverse transcriptase, which is necessary for transposition to occur. The Ds locus, which is the mutable site in corn discussed previously, is a nonautonomous element, because it lacks a trans- DR Reverse DR transcriptase/ posase gene. An element that is similar to Ds but contains a func- endonuclease tional transposase gene is called the Ac element, which stands for gene activator element. An Ac element provides a transposase gene that Non-LTR retrotransposon enables Ds to transpose. Therefore, nonautonomous TEs such as Ds can transpose only when Ac is present at another region in the (b) Elements that move by retrotransposition (via an RNA genome. The Ac element was present in McClintock’s strains. intermediate) F I G U RE 10.11 Common organization of DNA sequences in Transposase Catalyzes the Excision transposable elements. Direct repeats (DRs) are identical sequences and Insertion of Transposons found on both sides of all TEs. Inverted repeats (IRs) are at the ends of some transposable elements. Long terminal repeats (LTRs) are regions Now that we have considered the typical organization of TEs, let’s containing a large number of tandem repeats. examine the steps of the transposition process. The enzyme trans- posase catalyzes the removal of a transposon from its original site in the chromosome and its subsequent insertion at another loca- tion. A general scheme for simple transposition is shown in Depending on the particular IS element, the inverted repeats range Figure 10.12a. Transposase monomers first bind to the inverted from 9 to 40 bp in length. In addition, IS elements may contain a repeat sequences at the ends of the TE. The monomers then dimer- central region that encodes the enzyme transposase, which cata- ize, which brings the inverted repeats close together. The DNA is lyzes the transposition event. By comparison, a simple transposon cleaved between the inverted and direct repeats, which excises the carries one or more genes that are not required for transposition to TE from its original site within the chromosome. Transposase car- occur. For example, the simple transposon shown in Figure 10.11a ries the TE to a new site and cleaves the target DNA sequence at carries an antibiotic resistance gene. staggered recognition sites. The TE is then inserted into the target The organization of retrotransposons varies greatly. They DNA and ligated to it. are categorized based on their evolutionary relationship to retrovi- As shown in Figure 10.12b, the ligation of the transposable ruses. As described in Chapter 18, retroviruses are RNA viruses element into its new site initially leaves short gaps in the target DNA. that make a DNA copy that integrates into the host’s genome. Notice that the DNA sequences in these gaps are complementary to LTR retrotransposons are evolutionarily related to retroviruses. each other (in this case, ATGCT and TACGA). Therefore, when they These TEs have retained the ability to move around the genome, are filled in by DNA gap repair synthesis, the repair produces direct though, in most cases, they do not produce mature viral particles. repeats that flank both ends of the TE. These direct repeats are com- LTR retrotransposons are so named because they contain long mon features found adjacent to all TEs (see Figure 10.11). terminal repeats (LTRs) at both ends (Figure 10.11b). The LTRs Although the transposition process depicted in Figure 10.12 are typically a few hundred base pairs in length. Like their viral does not directly alter the number of TEs, simple transposition is counterparts, LTR retrotransposons may encode virally related known to increase their numbers in genomes, in some cases to fairly  10.5 TRANSPOSITION 241 Transposable element Transposase cleaves the target DNA at staggered sites. 5′ 3′ T Inverted A T G C Target repeat Transposase subunits A A bind to inverted repeats. T C G DNA Transposase 3′ 5′ subunit The transposable element is inserted into the target site. The dimerization of transposase 5′ 3′ subunits causes the TE to loop out. T A T G C A T A C G 3′ 5′ Transposable element DNA gap repair synthesis 5′ 3′ T T Transposase cleaves outside of the A T G C A T G C A A A A inverted repeats (see pink arrows), T C G T C G which excises the transposon from 3′ 5′ the chromosomal DNA. Transposable Excised TE element Direct repeats (b) The formation of direct repeats Excised TE is inserted into a new chromosomal location. F IG UR E 1 0. 1 2 Simple transposition. (a) Transposase removes the TE from its original site and inserts it into a new site. (b) A closer look (a) Movement of a transposon via transposase at how the insertion process creates direct repeats. high levels. How can this happen? The answer is that transposition LTR retrotransposons requires two key enzymes: reverse tran- often occurs around the time of DNA replication (Figure 10.13). scriptase and integrase. In this example, the cell already contains After a replication fork has passed a region containing a TE, two a retrotransposon known as Ty within its genome. This retrotrans- TEs will be found behind the fork—one in each of the replicated poson is transcribed into RNA. In a series of steps, reverse tran- regions. One of these TEs could then transpose from its original scriptase uses this RNA as a template to synthesize a location into a region ahead of the replication fork. After the repli- double-stranded DNA molecule. The long terminal repeats (LTRs) cation fork has passed this second region and DNA replication is at the ends of the double-stranded DNA are then recognized by completed, two TEs will be found in one of the chromosomes and integrase, which catalyzes the insertion of the DNA into the target one TE in the other chromosome. In this way, simple transposition chromosomal DNA. The integration of a retrotransposon can oc- can lead to an increase in TEs. We will discuss the biological signif- cur at many locations within the genome. Furthermore, because a icance of transposon proliferation later in this section. single retrotransposon can be copied into many RNA transcripts, retrotransposons may accumulate rapidly within a genome. The currently accepted model for the replication and integration Retrotransposons Use Reverse Transcriptase of non-LTR retrotransposons is called target-site primed reverse for Retrotransposition transcription (TPRT). As shown in Figure 10.15, the retrotranspo- Thus far, we have considered how transposons can move through- son is first transcribed into RNA with a polyA tail at the 3′ end. The out a genome. By comparison, retrotransposons use an RNA inter- target DNA site is recognized by an endonuclease, which may be en- mediate in their transposition mechanism. Let’s begin with LTR coded by the retrotransposon. This endonuclease recognizes a consen- retrotransposons. As shown in Figure 10.14, the movement of sus sequence of 5′-TTTTA-3′, and initially cuts just one of the DNA 242 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS Transposition Transposable Elements May Have Important Influences on Mutation and Evolution TE Over the past few decades, researchers have found that TEs prob- ably occur in the genomes of all species. Table 10.1 describes a few TEs that have been studied in great detail. As discussed ear- lier in this chapter, the genomes of eukaryotic species typically contain moderately and highly repetitive sequences. In some DNA replication proceeds past the TE point where the TE has been cases, these repetitive sequences are due to the proliferation of inserted. The top copy of the TE TEs. In the genomes of mammals, for example, LINEs are long then transposes ahead of the fork, interspersed elements that are usually 1000–10,000 bp in length where it is copied again. and occur in 20,000 to 1,000,000 copies per genome. In humans, TE a particular family of related LINEs called LINE-1, or L1, is found in about 500,000 copies and represents about 17% of the total human DNA! By comparison, SINEs are short interspersed elements that are less than 500 bp in length. A specific example TE TE of a SINE is the Alu sequence, present in about 1 million copies in the human genome. About 10% of the human genome is com- The bottom copy of DNA has 2 TEs. posed of this particular TE. LINEs and SINEs continue to proliferate in the human ge- F I G U RE 10.13 Increase in the number of copies of a trans- nome, but at a fairly low rate. In about 1 live birth in 100, an Alu posable element (TE) via simple transposition. In this example, a TE or an L1 (or both) sequence has been inserted into a new site in the that has already been replicated transposes to a new site that has not yet human genome. On rare occasions, a new insertion can disrupt a replicated. Following the completion of DNA replication, the TE has in- gene and cause phenotypic abnormalities. For example, new inser- creased in number. tions of L1 or Alu sequences into particular genes have been shown, on occasion, to be associated with diseases such as hemo- RNA Reverse philia, muscular dystrophy, and breast and colon cancer. transcriptase The relative abundance of TEs varies widely among differ- Integrase DNA ent species. As shown in Table 10.2, TEs can be quite prevalent in amphibians, mammals, and flowering plants, but tend to be less abundant in simpler organisms such as bacteria and yeast. The bi- Transcription ological significance of TEs in the evolution of prokaryotic and eukaryotic species remains a matter of debate. According to the selfish DNA hypothesis, TEs exist because they have characteris- tics that allow them to multiply within the chromosomal DNA of Ty living cells. In other words, they resemble parasites in the sense that they inhabit a cell without offering any selective advantage to the organism. They can proliferate as long as they do not harm the organism to the extent that they significantly disrupt survival. Ty Ty Ty Alternatively, other geneticists have argued that transposi- tional events are often deleterious. Therefore, TEs would be elim- FIGURE 10.14 Retrotransposition of an LTR retrotransposon. inated from the genome by natural selection if they did not also CONCEPT CHECK: What is the function of reverse transcriptase? offer a compensating advantage. Several potential advantages have been suggested. For example, TEs may cause greater genetic strands. The polyA tail of the retrotransposon RNA binds to this variability by promoting recombination. In addition, bacterial TEs nicked site due to A-T base pairing. Reverse transcriptase then uses the often carry an antibiotic resistance gene that provides the organ- target DNA as a primer and makes a DNA copy of the RNA, which is ism with a survival advantage. Researchers have also suggested why the process is named target-site primed reverse transcription. So that transposition may cause the insertion of exons from one gene that the retrotransposon will be fully integrated into the target DNA, into another gene, thereby producing a new gene with novel func- the endonuclease makes a second cut in the other DNA strand usually tion(s). This phenomenon, called exon shuffling, is described about 7–20 nucleotides away from the first cut. The retrotransposon in Chapter 27. Also, as discussed in Chapter 15, the ENCODE DNA is then ligated into the target site, perhaps by nonhomologous Project has revealed that much of the noncoding DNA in humans end joining, described in Chapter 19 (see Section 19.5). The mecha- may play a role in gene regulation, and that noncoding DNA could nism for synthesis of the other DNA strand of the retrotransposon is include segments that are derived from transposable elements. not completely understood. It could occur via DNA gap repair synthe- This controversy remains unresolved, but it is clear that TEs sis, described in Chapter 19 (see Section 19.6). can rapidly enter the genome of an organism and proliferate quickly.  Non-LTR retrotransposon Target DNA 5′ 3′ 5′ 3′ AAAA TAAAA TTTT ATTT T 3′ 5′ 3′ 5′ Target site is cut in one strand Transcription of retrotransposon by an endonuclease. Retrotransposon RNA with polyA tail 5′ 3′ TAAAA 5′ 3′ ATTT T AAAA 3′ 5′ First cut Retrotransposon RNA binds to the site due to A-T base pairing. 5′ 3′ TAAAA A 3′ 5′ T T TA A T AA 3′ 5′ Reverse transcriptase copies the RNA into DNA. 5′ 3′ TAAAA A 3′ 5′ T T TA A T AA Target-site primed reverse transcription 5′ 3′ The endonuclease cuts the other DNA strand. Second cut 5′ 3′ TAAAA A 3′ 5′ T T TA A T AA 5′ 3′ The RNA is degraded and then the retrotransposon is integrated into the target site. This leaves gaps in the DNA that are filled in by DNA polymerase and ligase (shown in blue). 5′ 3′ TAAAA AAAA ATTT T TTTT 3′ 5′ Non-LTR retrotransposon at a new site F I G U R E 10. 15 Retrotransposition of a non-LTR retrotransposon. 243 244 C H A P T E R 1 0 : : MOLECULAR STRUCTURE OF CHROMOSOMES AND TRANSPOSABLE ELEMENTS TAB L E 10.1 Examples of Transposable Elements Element Type Approximate Length (bp) Description Bacterial IS1 Transposon 768 An insertion element that is commonly found in five to eight copies in E. coli. Tn10 Transposon 9300 One of many different bacterial transposons that carries an antibiotic resistance gene. Tn951 Transposon 16,600 A transposon that provides bacteria with genes that allow them to metabolize lactose. Yeast Ty element Retrotransposon 6300 Found in S. cerevisiae in about 35 copies per genome. Fruit Fly P element Transposon 500–3000 A transposon that may be found in 30–50 copies in P strains of Drosophila. It is absent from M strains. Copia-like element Retrotransposon 5000–8000 One of a family of TEs found in Drosophila, which vary slightly in their lengths and sequences. Typically, each family member is found in about 5–100 copies per genome. Humans Alu sequence Retrotransposon 300 A SINE found in about 1,000,000 copies in the human genome. L1 Retrotransposon 6500 A LINE found in about 500,000 copies in the human genome. Plants Ac or Ds Transposon 4500 Ac is an autonomous transposon found in corn and other plant species. It carries a transposase gene. Ds is a nonautonomous version that lacks a functional transposase gene. Opie Retrotransposon 9000 A retrotransposon found in plants that is related to the copia-like elements found in animals. In Drosophila melanogaster, for example, a TE known strains collected prior to the 1950s. This observation underscores as a P element was probably introduced into this species in the the surprising ability of TEs to infiltrate a population of organisms. 1950s. Laboratory stocks of D. melanogaster collected prior to this Transposable elements have a variety of effects on chro- time do not contain P elements. Remarkably, in the last 60 years, the mosome structure and gene expression (Table 10.3). Many of P element has expanded throughout D. melanogaster populations these outcomes are likely to be harmful. Usually, transposition is worldwide. The only strains without the P element are laboratory a relatively rare event that occurs only in