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Selfish DNA
Selfish D NA 1805
Self-Fertilization
Selfish DNA
J Hodgkin
H Y Wong
Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1169
Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1170
Self-fertilization occurs when an individual is capable of generating both male and female gametes, and using the former (sperm) to fertilize the latter (eggs), thereby producing self-progeny. The majority of animal species reproduce by cross-fertilization, either with separate male and female sexes, or with a hermaphrodite sex that is specialized to avoid self-fertilization. Reproduction by cross-fertilization increases genetic diversity by sampling the genomes of two different individuals, and so creating new combinations in their offspring. Self-fertilization can also create diversity in progeny genotypes, because both male and female gametes are usually produced with meiotic recombination, but a purely selfing population will steadily lose heterozygosity at any given locus, and is therefore vulnerable to inbreeding depression. Self-fertility nevertheless occurs widely in the animal kingdom, in a variety of invertebrate groups. There are several obvious advantages to self-fertility, of which the most important is the avoidance of the twofold `cost of sex': all individuals in a self-fertile population are capable of producing progeny, in contrast to a population of males and females, in which only the females produce progeny. Self-fertility also has the advantages that a single organism can colonize a new habitat, and that individuals do not need to invest time and resources in finding mating partners. The same advantages of rapid population growth and efficient colonization apply also to organisms that reproduce amictically (parthenogenetically), but such organisms do not even undergo meiotic recombination, and therefore have no ability to create new genetic combinations from one generation to the next. In general, it is believed that completely amictic populations are more likely to go extinct than those with some degree of genetic exchange. Reproduction by self-fertilization represents a compromise, especially for organisms with the capacity for both selffertilization and cross-fertilization. Examples of this strategy are provided by species with hermaphrodite sexes that are capable of both selfing and crossing, or species such as the laboratory nematode Caenorhabditis elegans, which has populations consisting mostly of self-fertile hermaphrodites with rare males that can cross-fertilize the hermaphrodites.
Theoretical Concepts
See also: Caenorhabditis elegans; Fertilization; Hermaphrodite; Parthenogenesis, Mammalian
The assertion that organisms are simply DNA's way of producing more DNA has been made so often that it is hard to remember who made it first.
So begins one of two classic papers (Doolittle and Sapienza (1980); Orgel and Crick, 1980), which developed the concept of selfish DNA and sparked off a debate which is still not altogether resolved. Whilst Dawkins (1976, p. 47) also mentioned the idea of selfish DNA, his focus was primarily on `selfish genes': a phrase he used to describe all genes, in order to emphasize that genes are selected solely on the basis of their own propensity to increase in number. One way in which this increase occurs is when the DNA sequence provides a function that increases the general reproductive output (fitness) of the organism in which it is found, but there are two other ways in which a sequence can increase in number over time. The first is by subverting the process of inheritance such that, at a single locus, an individual heterozygous for the sequence has a greater than 50% chance of passing it to an offspring. This can be accomplished by mechanisms such as meiotic drive which promotes one chromosome to the detriment of the other. The second way is for sequences to replicate across the genome, so that many copies may be found in different locations in the same genome. It should be emphasized that both of these methods only require sequences to be inherited vertically, from parent to offspring. Those replicating sequences that are regularly transmitted horizontally are usually regarded as viruses or virus-like organisms. Sometimes, but not always, the spread of these self-promoting elements reduces the fitness of the bearer. This is only likely to occur in sexually outcrossing species, where the element can be selected relatively independently of the rest of the genome. The result of this collision of interests is genomic conflict, the demonstration of which is probably the clearest evidence of the `selfish' nature of a sequence.
Definitions
Since the term `selfish gene' can be used to describe any gene, genetic elements that promote themselves without necessarily benefiting the organism in which they are found, can be referred to as `ultra-selfish genes,' `selfish genetic elements,' or `outlaw genes.' This avoids
1806
Selfish D NA
the terminological confusion witnessed in the use of `selfish gene' and `selfish DNA' in the respective titles of the two previously mentioned papers. Nevertheless, it is becoming common to find the name `selfish gene' being used specifically to refer to these sequences. `Selfish DNA' is a term often used rather vaguely to refer to a self-promoting element which works at a molecular level. Meiotic drive genes are not usually thought of as selfish DNA, and it seems sensible to restrict the term to self-promoting elements which multiply within a genome (although some spread in both ways). Some authors prefer the less anthropomorphic terminology `parasitic DNA,' and perhaps more accurate still is the term `symbiotic DNA.' This emphasizes that the DNA is not distinguished by its physical effects. Indeed, one of the main points emphasized by Doolittle and Sapienza (1980) was that presence or absence of these sequences often has no specific effect on the phenotype. However, gross phenotypic effects can sometimes be seen, such as sterility and other defects in Drosophila hybrids. This hybrid dysgenesis is due to the introduction of selfish DNA, in the form of P elements, into genomes which have no mechanism to prevent its excessive duplication. In addition, it is now known that organisms sometimes use selfish elements for particular purposes (see below, `Coevolution of selfish DNA and host'). It thus seems unwise to define selfish DNA by the absence of a specific phenotype. Nevertheless, one successful strategy for a replicating sequence is to reduce phenotypic effects so as to cause as little disturbance as possible to the organism. `Junk DNA' is used to refer to DNA which is sequence-independent: the sequence order does not lead to any recognizable function. Selfish DNA or normal genes may lose functionality and become `junk.' Mutation may then render their origin uncertain.
Genetic Mechanisms This section presents only a brief summary of some types of selfish DNA. For greater detail, the reader is referred to more specific encyclopedia entries. Generally, selfish DNA sequences provide some of the machinery needed for self-replication, but also rely on cellular DNA replication mechanisms.
Transposable Elements
Transposons are perhaps the most common form of selfish DNA, and eukaryotic genomes contain many nonfunctional remnants of transposons as well as functional elements. They fall into class I and class II elements depending on their method of transposition. Class I elements (retroelements) use a `copy-and paste' mechanism whereby reverse transcriptase makes
a DNA copy of the element from transcribed RNA, which is then integrated elsewhere in the genome. One type, the retrotransposons, bear close similarity to retroviruses, and evolution from retrotransposons to retroviruses, and vice versa, is likely. Indeed, the gypsy retrotransposon in Drosophila can be passed from one individual to another via food, and could be said to be a virus. A few retroelements do not themselves code for reverse transcriptase, presumably requiring it to be provided by other elements. This is the case for Alu, an element derived from a normal host gene, which makes up about 5% of human DNA. It could be said that these are hyperparasitic DNA, parasitizing the resources of `normal' parasitic class I elements, their reduced size giving faster and more accurate replication, as well as making mutational inactivation less likely. Indeed, most transposons have nonautonomous variants which, like Alu, `borrow' some of the genes needed for transposition. Class II transposons, such as the Drosophila P element, use a `cut-and-paste' method, excising themselves from the genome and reinserting elsewhere. At first sight, this would seem not to increase the number of elements present, but high copy numbers suggest that they can replicate, and it has been suggested that this occurs due to transposition from replicated to unreplicated regions during normal DNA duplication. Transposons are thought to have an insertion bias for noncoding areas, such as heterochromatin or even preexisting transposons, where their phenotypic effect is minimal. Even so, a large fraction of mutations in most organisms are caused by transposable elements inserting and excising. Transposition in somatic cells gives no long-term advantage to the sequence, and may endanger the host. This is presumably the reason for transposons such as P elements only being active in germ-line cells. Concentration of transposons on the germ-line is seen in an extreme form in hypotrich ciliates. These unicellular organisms use a separate nucleus for somatic gene transcription, which only contains 5% of the germline DNA. A substantial fraction of the excised DNA consists of transposons.
Type I and Type II Introns
These self-splicing introns are unlike other introns: not only do they have a fairly conserved sequence, but in addition to being present in eukaryotic nuclei, multiple copies are also found in prokaryotes and organelles. Their RNA sequence is catalytic, splicing itself out of any length of RNA in which it occurs, hence concealing its presence when inserted in a coding region. Type I introns have the best-studied `selfish' behavior. They can add themselves to alleles
Selfish D NA 1807 without the intron at the corresponding locus on the homologous chromosome. This is done by coding for a restriction endonuclease which recognizes and chops DNA at the locus, forcing repair to take place using the intron-containing sequence as a template. Alleles containing the intron cannot be cut, as the intron spans the restriction site. This biased gene conversion process is known as homing, and may also be responsible for the transfer of the intron to other loci. Perhaps the most intriguing behavior is endonuclease war, in which different type I introns present in separate bacteriophages, preferentially cut each others splice sites, even when the intron is present. When both phages infect the same host, a selfish DNA battle may ensue, with each intron trying to deplete the available splice sites so as to reduce the risk of being spliced into by the other sequence. Type II introns code for reverse-transcriptase-like proteins, which suggests mechanisms for autonomous self-replication. Similarities in splicing mechanisms suggest that a type-II-like sequence may well have been ancestral to normal eukaryotic introns.
Supernumerary Chromosomes
Ten to fifteen percent of plant and animal species possess B chromosomes: chromosomes which are generally small and seem to be dispensable, since they are present in some, but not all, individuals. They are often present in multiple copies, and were first suggested as parasitic elements as early as 1945. Their probability of transmission is increased in species that do not use all four meiotic products, by preferential movement into those cells which become true gametes. They may also move preferentially into germline cells in development. These transmission methods can lead to a cumulative increase in the number of B chromosomes. Plasmids may also be considered as extra chromosomes, and the probable evolution of viruses from plasmids shows their potentially selfish nature.
Tandemly Repeated DNA
This is also known as satellite DNA, and consists of a single sequence repeated many times over. It is caused by slippage, where misalignment during meiotic recombination leaves one chromosome with a higher number of copies and the other with a lower number. A few satellite sequences may have organismal functions, but many do not. Those that do not are often regarded as junk DNA, but are clearly sequencedependent: although it is never translated into protein, changing a sequence in the array will reduce slippage. They could be said to be `selfishly' using the mechanism of crossover to replicate, as although their replication is extremely limited and elimination as well as
amplification can occur, the world disproportionately contains the results of amplification. Evidence that tandemly repeated DNA can be transferred between loci also suggests the potential for selfish-DNA-like behavior.
Evidence and Controversy The concept of selfish DNA is now generally accepted: it is indisputable that these sequences multiply in the genome, and that they can cause problems for the organism in which they reside. Debate has instead focused on the role of selfish DNA in evolution.
The C Value Paradox
The C value paradox is that the amount of DNA in a haploid genome (the 1C value) does not seem to correspond strongly to the complexity of an organism, and 1C values can be extremely variable. Some salamanders have more than 30 times the amount of DNA per cell as humans, and within genera such as the sunflowers, Helianthus, some species have 1C values four times greater than others. Much DNA in the cell is present as repetitive sequences of varying lengths, often intermediate repeat sequences which are mostly selfish elements. Over 50% of the maize genome probably consists of retroelements. A strong correlation between the C value and nuclear size, cell size, and cell cycle time has led some to suggest that selection on these factors maintains a C value which is more or less optimal for the organism. According to this hypothesis, the organism requires a certain amount of DNA, which could consist of any sequence. Selfish DNA is particularly good at competing for this `resource,' hence its presence in the genome. The organism can regulate the C value, for example, by deleting stretches of sequence in heterochromatic regions. The organism thus has the final say in the C value, and selfish DNA does not explain the paradox. The opposing argument is that selfish DNA can increase the C value to well above that which is best for the organism: conflict between selfish elements and the rest of the genome results in different C values depending on which is winning. Under this view, selfish DNA can explain much of the paradox. One factor suggesting that organisms have ultimate control over their genome size is the presence of genomes which contain mostly coding DNA, but have no major reason to prevent the build-up of selfish genetic elements. Although bacterial genomes have little surplus DNA, this can be explained by strong selection for rapid replication. Organelle genomes are similarly economical, but this may be due to competition among themselves for representation in the cell or in the
1808
Sel f-Sp l ic in g
gametes. Indeed, petite mutants of yeast contain defective mitochondria which are successful due to their increased replication rate, but do not provide a respiratory function (they have been suggested as selfish DNA in their own right). Since the methods by which selection acts on increased genome size are still a topic of debate, it seems likely that the issue will remain controversial.
Intron Evolution
Because prokaryotes have no introns, it is tempting to assume that introns are a late addition to the eukaryotic genome. By contrast, the introns-early hypothesis states that the ancestor of eukaryotes already possessed introns, and that introns were lost in prokaryotes. It has close links with the `exon theory of genes' which states that exon shuffling of originally small exons, each of which provides a functional domain of a protein, is the origin of the eukaryotic genome we see today. This leads to a selective advantage for possessing introns, which now provide an important organismal function. The introns-late hypothesis considers that introns are primarily the result of more recent, selfish DNA movement. Generally, introns at different loci have quite different sequences, suggesting that, although they might have been selfish DNA, they have been inactive for a reasonable length of time. More convincingly, a few intron positions are shared between plants and animals. This could be evidence for early introns (although the plant/animal split is later than the prokaryote/eukaryote one), or could conceivably be due to insertional bias. It seems extremely probable that many genes arose by exon shuffling: an example of gene formation of this sort has been found recently in Drosophila. In addition, there is slight evidence that introns do correspond to boundaries between protein domains. Whether this is due to exons evolving to provide this function and relatively recently co-opting introns based on selfish DNA to an organismal function, or whether the system started off in this form, is essentially still unresolved.
Coevolution of Selfish DNA and Host
The possibility that introns may have been selfish DNA, which now provides a function for the rest of the genome, is one of many examples of coevolution which have been suggested by recent research. Another is the telomere structure in Drosophila and some ciliates, which consists of repeated retroelements: the ends of the chromosome are extended by retrotransposition. In many plants, the regulatory regions of several genes are encoded by the mobile elements Tourist and Stowaway, and the use of
plasmids to transfer antibiotic resistance between bacteria is well known. Finally, it is often suggested that a function of transposons is to provide new mutations, especially when accidentally transposing parts of the host sequence to new loci. This last suggestion is clearly an important factor in evolution, but is unlikely to provide short-term advantage. It is best interpreted as the host adapting to what is increasingly recognized as a very fluid genome.
Further Reading
Zeyl C and Bell G (1996) Symbiotic DNA in eukaryotic genomes. Trends in Ecology and Evolution 11: 10±15.
References
Dawkins R (1976) The Selfish Gene. Oxford: Oxford University Press. Doolittle WF and Sapienza C (1980) Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601±603. Orgel LE and Crick FHC (1980) Selfish DNA: the ultimate parasite. Nature 284: 604±607.
See also: C-Value Paradox; Intron Homing; Introns and Exons; Satellite DNA
Self-Splicing See: Introns and Exons
Semiconservative Replication Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.2016
Semiconservative replication is the universal system of DNA replication whereby strands of a parental duplex DNA molecule separate, each then acting as a template for the synthesis of a new complementary strand. See also: Replication
Semidiscontinuous Replication Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.2017
Semidiscontinuous replication is the mode of DNA replication whereby one new strand is synthesized
Self-Fertilization
Selfish DNA
J Hodgkin
H Y Wong
Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1169
Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1170
Self-fertilization occurs when an individual is capable of generating both male and female gametes, and using the former (sperm) to fertilize the latter (eggs), thereby producing self-progeny. The majority of animal species reproduce by cross-fertilization, either with separate male and female sexes, or with a hermaphrodite sex that is specialized to avoid self-fertilization. Reproduction by cross-fertilization increases genetic diversity by sampling the genomes of two different individuals, and so creating new combinations in their offspring. Self-fertilization can also create diversity in progeny genotypes, because both male and female gametes are usually produced with meiotic recombination, but a purely selfing population will steadily lose heterozygosity at any given locus, and is therefore vulnerable to inbreeding depression. Self-fertility nevertheless occurs widely in the animal kingdom, in a variety of invertebrate groups. There are several obvious advantages to self-fertility, of which the most important is the avoidance of the twofold `cost of sex': all individuals in a self-fertile population are capable of producing progeny, in contrast to a population of males and females, in which only the females produce progeny. Self-fertility also has the advantages that a single organism can colonize a new habitat, and that individuals do not need to invest time and resources in finding mating partners. The same advantages of rapid population growth and efficient colonization apply also to organisms that reproduce amictically (parthenogenetically), but such organisms do not even undergo meiotic recombination, and therefore have no ability to create new genetic combinations from one generation to the next. In general, it is believed that completely amictic populations are more likely to go extinct than those with some degree of genetic exchange. Reproduction by self-fertilization represents a compromise, especially for organisms with the capacity for both selffertilization and cross-fertilization. Examples of this strategy are provided by species with hermaphrodite sexes that are capable of both selfing and crossing, or species such as the laboratory nematode Caenorhabditis elegans, which has populations consisting mostly of self-fertile hermaphrodites with rare males that can cross-fertilize the hermaphrodites.
Theoretical Concepts
See also: Caenorhabditis elegans; Fertilization; Hermaphrodite; Parthenogenesis, Mammalian
The assertion that organisms are simply DNA's way of producing more DNA has been made so often that it is hard to remember who made it first.
So begins one of two classic papers (Doolittle and Sapienza (1980); Orgel and Crick, 1980), which developed the concept of selfish DNA and sparked off a debate which is still not altogether resolved. Whilst Dawkins (1976, p. 47) also mentioned the idea of selfish DNA, his focus was primarily on `selfish genes': a phrase he used to describe all genes, in order to emphasize that genes are selected solely on the basis of their own propensity to increase in number. One way in which this increase occurs is when the DNA sequence provides a function that increases the general reproductive output (fitness) of the organism in which it is found, but there are two other ways in which a sequence can increase in number over time. The first is by subverting the process of inheritance such that, at a single locus, an individual heterozygous for the sequence has a greater than 50% chance of passing it to an offspring. This can be accomplished by mechanisms such as meiotic drive which promotes one chromosome to the detriment of the other. The second way is for sequences to replicate across the genome, so that many copies may be found in different locations in the same genome. It should be emphasized that both of these methods only require sequences to be inherited vertically, from parent to offspring. Those replicating sequences that are regularly transmitted horizontally are usually regarded as viruses or virus-like organisms. Sometimes, but not always, the spread of these self-promoting elements reduces the fitness of the bearer. This is only likely to occur in sexually outcrossing species, where the element can be selected relatively independently of the rest of the genome. The result of this collision of interests is genomic conflict, the demonstration of which is probably the clearest evidence of the `selfish' nature of a sequence.
Definitions
Since the term `selfish gene' can be used to describe any gene, genetic elements that promote themselves without necessarily benefiting the organism in which they are found, can be referred to as `ultra-selfish genes,' `selfish genetic elements,' or `outlaw genes.' This avoids
1806
Selfish D NA
the terminological confusion witnessed in the use of `selfish gene' and `selfish DNA' in the respective titles of the two previously mentioned papers. Nevertheless, it is becoming common to find the name `selfish gene' being used specifically to refer to these sequences. `Selfish DNA' is a term often used rather vaguely to refer to a self-promoting element which works at a molecular level. Meiotic drive genes are not usually thought of as selfish DNA, and it seems sensible to restrict the term to self-promoting elements which multiply within a genome (although some spread in both ways). Some authors prefer the less anthropomorphic terminology `parasitic DNA,' and perhaps more accurate still is the term `symbiotic DNA.' This emphasizes that the DNA is not distinguished by its physical effects. Indeed, one of the main points emphasized by Doolittle and Sapienza (1980) was that presence or absence of these sequences often has no specific effect on the phenotype. However, gross phenotypic effects can sometimes be seen, such as sterility and other defects in Drosophila hybrids. This hybrid dysgenesis is due to the introduction of selfish DNA, in the form of P elements, into genomes which have no mechanism to prevent its excessive duplication. In addition, it is now known that organisms sometimes use selfish elements for particular purposes (see below, `Coevolution of selfish DNA and host'). It thus seems unwise to define selfish DNA by the absence of a specific phenotype. Nevertheless, one successful strategy for a replicating sequence is to reduce phenotypic effects so as to cause as little disturbance as possible to the organism. `Junk DNA' is used to refer to DNA which is sequence-independent: the sequence order does not lead to any recognizable function. Selfish DNA or normal genes may lose functionality and become `junk.' Mutation may then render their origin uncertain.
Genetic Mechanisms This section presents only a brief summary of some types of selfish DNA. For greater detail, the reader is referred to more specific encyclopedia entries. Generally, selfish DNA sequences provide some of the machinery needed for self-replication, but also rely on cellular DNA replication mechanisms.
Transposable Elements
Transposons are perhaps the most common form of selfish DNA, and eukaryotic genomes contain many nonfunctional remnants of transposons as well as functional elements. They fall into class I and class II elements depending on their method of transposition. Class I elements (retroelements) use a `copy-and paste' mechanism whereby reverse transcriptase makes
a DNA copy of the element from transcribed RNA, which is then integrated elsewhere in the genome. One type, the retrotransposons, bear close similarity to retroviruses, and evolution from retrotransposons to retroviruses, and vice versa, is likely. Indeed, the gypsy retrotransposon in Drosophila can be passed from one individual to another via food, and could be said to be a virus. A few retroelements do not themselves code for reverse transcriptase, presumably requiring it to be provided by other elements. This is the case for Alu, an element derived from a normal host gene, which makes up about 5% of human DNA. It could be said that these are hyperparasitic DNA, parasitizing the resources of `normal' parasitic class I elements, their reduced size giving faster and more accurate replication, as well as making mutational inactivation less likely. Indeed, most transposons have nonautonomous variants which, like Alu, `borrow' some of the genes needed for transposition. Class II transposons, such as the Drosophila P element, use a `cut-and-paste' method, excising themselves from the genome and reinserting elsewhere. At first sight, this would seem not to increase the number of elements present, but high copy numbers suggest that they can replicate, and it has been suggested that this occurs due to transposition from replicated to unreplicated regions during normal DNA duplication. Transposons are thought to have an insertion bias for noncoding areas, such as heterochromatin or even preexisting transposons, where their phenotypic effect is minimal. Even so, a large fraction of mutations in most organisms are caused by transposable elements inserting and excising. Transposition in somatic cells gives no long-term advantage to the sequence, and may endanger the host. This is presumably the reason for transposons such as P elements only being active in germ-line cells. Concentration of transposons on the germ-line is seen in an extreme form in hypotrich ciliates. These unicellular organisms use a separate nucleus for somatic gene transcription, which only contains 5% of the germline DNA. A substantial fraction of the excised DNA consists of transposons.
Type I and Type II Introns
These self-splicing introns are unlike other introns: not only do they have a fairly conserved sequence, but in addition to being present in eukaryotic nuclei, multiple copies are also found in prokaryotes and organelles. Their RNA sequence is catalytic, splicing itself out of any length of RNA in which it occurs, hence concealing its presence when inserted in a coding region. Type I introns have the best-studied `selfish' behavior. They can add themselves to alleles
Selfish D NA 1807 without the intron at the corresponding locus on the homologous chromosome. This is done by coding for a restriction endonuclease which recognizes and chops DNA at the locus, forcing repair to take place using the intron-containing sequence as a template. Alleles containing the intron cannot be cut, as the intron spans the restriction site. This biased gene conversion process is known as homing, and may also be responsible for the transfer of the intron to other loci. Perhaps the most intriguing behavior is endonuclease war, in which different type I introns present in separate bacteriophages, preferentially cut each others splice sites, even when the intron is present. When both phages infect the same host, a selfish DNA battle may ensue, with each intron trying to deplete the available splice sites so as to reduce the risk of being spliced into by the other sequence. Type II introns code for reverse-transcriptase-like proteins, which suggests mechanisms for autonomous self-replication. Similarities in splicing mechanisms suggest that a type-II-like sequence may well have been ancestral to normal eukaryotic introns.
Supernumerary Chromosomes
Ten to fifteen percent of plant and animal species possess B chromosomes: chromosomes which are generally small and seem to be dispensable, since they are present in some, but not all, individuals. They are often present in multiple copies, and were first suggested as parasitic elements as early as 1945. Their probability of transmission is increased in species that do not use all four meiotic products, by preferential movement into those cells which become true gametes. They may also move preferentially into germline cells in development. These transmission methods can lead to a cumulative increase in the number of B chromosomes. Plasmids may also be considered as extra chromosomes, and the probable evolution of viruses from plasmids shows their potentially selfish nature.
Tandemly Repeated DNA
This is also known as satellite DNA, and consists of a single sequence repeated many times over. It is caused by slippage, where misalignment during meiotic recombination leaves one chromosome with a higher number of copies and the other with a lower number. A few satellite sequences may have organismal functions, but many do not. Those that do not are often regarded as junk DNA, but are clearly sequencedependent: although it is never translated into protein, changing a sequence in the array will reduce slippage. They could be said to be `selfishly' using the mechanism of crossover to replicate, as although their replication is extremely limited and elimination as well as
amplification can occur, the world disproportionately contains the results of amplification. Evidence that tandemly repeated DNA can be transferred between loci also suggests the potential for selfish-DNA-like behavior.
Evidence and Controversy The concept of selfish DNA is now generally accepted: it is indisputable that these sequences multiply in the genome, and that they can cause problems for the organism in which they reside. Debate has instead focused on the role of selfish DNA in evolution.
The C Value Paradox
The C value paradox is that the amount of DNA in a haploid genome (the 1C value) does not seem to correspond strongly to the complexity of an organism, and 1C values can be extremely variable. Some salamanders have more than 30 times the amount of DNA per cell as humans, and within genera such as the sunflowers, Helianthus, some species have 1C values four times greater than others. Much DNA in the cell is present as repetitive sequences of varying lengths, often intermediate repeat sequences which are mostly selfish elements. Over 50% of the maize genome probably consists of retroelements. A strong correlation between the C value and nuclear size, cell size, and cell cycle time has led some to suggest that selection on these factors maintains a C value which is more or less optimal for the organism. According to this hypothesis, the organism requires a certain amount of DNA, which could consist of any sequence. Selfish DNA is particularly good at competing for this `resource,' hence its presence in the genome. The organism can regulate the C value, for example, by deleting stretches of sequence in heterochromatic regions. The organism thus has the final say in the C value, and selfish DNA does not explain the paradox. The opposing argument is that selfish DNA can increase the C value to well above that which is best for the organism: conflict between selfish elements and the rest of the genome results in different C values depending on which is winning. Under this view, selfish DNA can explain much of the paradox. One factor suggesting that organisms have ultimate control over their genome size is the presence of genomes which contain mostly coding DNA, but have no major reason to prevent the build-up of selfish genetic elements. Although bacterial genomes have little surplus DNA, this can be explained by strong selection for rapid replication. Organelle genomes are similarly economical, but this may be due to competition among themselves for representation in the cell or in the
1808
Sel f-Sp l ic in g
gametes. Indeed, petite mutants of yeast contain defective mitochondria which are successful due to their increased replication rate, but do not provide a respiratory function (they have been suggested as selfish DNA in their own right). Since the methods by which selection acts on increased genome size are still a topic of debate, it seems likely that the issue will remain controversial.
Intron Evolution
Because prokaryotes have no introns, it is tempting to assume that introns are a late addition to the eukaryotic genome. By contrast, the introns-early hypothesis states that the ancestor of eukaryotes already possessed introns, and that introns were lost in prokaryotes. It has close links with the `exon theory of genes' which states that exon shuffling of originally small exons, each of which provides a functional domain of a protein, is the origin of the eukaryotic genome we see today. This leads to a selective advantage for possessing introns, which now provide an important organismal function. The introns-late hypothesis considers that introns are primarily the result of more recent, selfish DNA movement. Generally, introns at different loci have quite different sequences, suggesting that, although they might have been selfish DNA, they have been inactive for a reasonable length of time. More convincingly, a few intron positions are shared between plants and animals. This could be evidence for early introns (although the plant/animal split is later than the prokaryote/eukaryote one), or could conceivably be due to insertional bias. It seems extremely probable that many genes arose by exon shuffling: an example of gene formation of this sort has been found recently in Drosophila. In addition, there is slight evidence that introns do correspond to boundaries between protein domains. Whether this is due to exons evolving to provide this function and relatively recently co-opting introns based on selfish DNA to an organismal function, or whether the system started off in this form, is essentially still unresolved.
Coevolution of Selfish DNA and Host
The possibility that introns may have been selfish DNA, which now provides a function for the rest of the genome, is one of many examples of coevolution which have been suggested by recent research. Another is the telomere structure in Drosophila and some ciliates, which consists of repeated retroelements: the ends of the chromosome are extended by retrotransposition. In many plants, the regulatory regions of several genes are encoded by the mobile elements Tourist and Stowaway, and the use of
plasmids to transfer antibiotic resistance between bacteria is well known. Finally, it is often suggested that a function of transposons is to provide new mutations, especially when accidentally transposing parts of the host sequence to new loci. This last suggestion is clearly an important factor in evolution, but is unlikely to provide short-term advantage. It is best interpreted as the host adapting to what is increasingly recognized as a very fluid genome.
Further Reading
Zeyl C and Bell G (1996) Symbiotic DNA in eukaryotic genomes. Trends in Ecology and Evolution 11: 10±15.
References
Dawkins R (1976) The Selfish Gene. Oxford: Oxford University Press. Doolittle WF and Sapienza C (1980) Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601±603. Orgel LE and Crick FHC (1980) Selfish DNA: the ultimate parasite. Nature 284: 604±607.
See also: C-Value Paradox; Intron Homing; Introns and Exons; Satellite DNA
Self-Splicing See: Introns and Exons
Semiconservative Replication Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.2016
Semiconservative replication is the universal system of DNA replication whereby strands of a parental duplex DNA molecule separate, each then acting as a template for the synthesis of a new complementary strand. See also: Replication
Semidiscontinuous Replication Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.2017
Semidiscontinuous replication is the mode of DNA replication whereby one new strand is synthesized