Transposons

Transposons are repetitive mobile sequences that are dispersed throughout the genome. There are two broad classes of transposons: DNA transposons and retrotransposons. DNA transposons generally move within the genome as pieces of DNA, cutting and pasting themselves into new genomic locations. Retrotransposons duplicate through an RNA intermediate, usually with the original transposon remaining at its original site where it is transcribed. The resulting RNA transcript is then reverse transcribed into DNA, which then can integrate into new genomic locations. In either event, this phenotype of transposition is expressed within cells and can be a target of selection, with the within-individual selection favoring those sequences that can make more copies of themselves. A transposon that can make many copies of itself and disperse throughout the genome has a much greater chance of being passed on through a gamete to the next generation than another transposon that has poor replicative abilities. For example, a transposon that exists as a single copy on an autosome will be passed on to the next generation in only half of the gametes. However, a trans-poson that has produced many copies that are dispersed across many locations ensures that virtually all gametes will carry multiple copies to the next generation. In this manner, those transposons most successful at the genomic level also have greater success in spreading throughout the population. As a result, the genomes of many organisms are filled with many different transposons, with the copy number of particular types of transposons sometimes going into the millions. For example, just one class of retrotransposons called human endogenous retrovirus (HERV) makes up 7% of the human genome (Prak and Kazazian 2000).

Transposons are units of selection that can have multiple targets of selection. In addition to selection within cells on their ability to transpose and replicate within genomes, transposons often affect fitness at the individual level (Cooper 1999; Kidwell and Lisch 2000; Prak and Kazazian 2000). Just as we saw for the t complex in mice, the evolutionary dynamics of transposons must take into account multiple targets of selection, and phrasing the evolution of transposons only as "selfish" DNA that parasitizes the genome is inappropriate and misleading. For example, different types of transposons have inserted into the promoter of the hsp70Ba gene that codes for the stress-inducible molecular chaperone Hsp70 in Drosophila melanogaster (Lerman et al. 2003). These transposon insertions underlie the natural variation found in the expression of this gene, and this in turn directly alters two components of individual fitness, inducible thermotolerance and female reproductive success. Another example is provided by the Alu transposon, which exists as roughly a million copies per human genome. Alu elements frequently insert into noncoding regions and modify the expression of nearby genes (Cooper 1999). For example, the estrogen responsiveness of the human breast cancer gene (BRCA1) appears to have been conferred by an Alu element located within the promoter region of the gene. An Alu sequence in the last intron of the human CD8A gene modulates the activity of an adjacent T-lymphocyte-specific enhancer. This particular Alu sequence differs at seven nucleotides from its probable source Alu sequence. Two of these nucleotide changes are in an area of the derived sequence that acts as a transcription factor binding site, and site-directed mutagenesis indicates that both nucleotide substitutions are necessary for this function, These results suggest that these nucleotide changes were due to selection at the individual level in this specific inserted Alu sequence. Thus, this Alu unit of selection seems to have been shaped by positive selection for its phenotypic impact at the individual level.

Indeed, selection at the individual level can sometimes co-opt completely the subsequent evolution of a transposon. One of the most startling examples of this is the jawed vertebrate immune system that mounts an antigen-specific response to infection (Agrawal 2000). Vertebrates generally have much longer generation lengths than the infectious agents that attack them, yet the vertebrate immune system effectively allows genetic diversity to be generated and selected on a rapid time scale within individuals. This nongermline genetic diversity can be generated because our antigen receptor genes are divided into gene segments, called V and J, and a third segment called D at some loci. DNA rearrangements, called V(D)J recombination, of these segments can be generated within the cells of our immune system. This combinatorial mechanism generates huge amounts of variation in the antigen recognition portion of the receptor, and mechanisms exist to preferentially select at the cellular level within individuals those combinations that are most effective in dealing with a particular infectious agent. Note that our immune response represents a type of selection at a level below the individual and involves the movement of DNA elements. These features suggest that V(D)J recombination has evolved from a transposable element, and recent studies on the molecular details of this recombination mechanism strongly indicate that this unique feature of the jawed vertebrate immune system evolved from a transposable element called the RAG transposon. This novel immune system, co-opted from a transposon, constitutes one of the most important adaptive breakthroughs in the jawed vertebrates, an adaptation that arose 450 MYA, and retains its critical adaptive significance to the present. Indeed, one can reasonably speculate that humans, along with many other jawed vertebrates, could have never evolved if it had not been for this RAG transposon.

Some transposons display a qualitatively different aspect to their evolution not seen in the other targets of selection discussed previously. In all previous cases, no matter how intense the selection is below the level of the individual, the selective response of the unit of selection was always constrained and shaped by the necessity of passing on to the next generation through a gamete. However, some transposons have the ability to "infect" a new individual in a manner independent of gametic transmission. This infectious type of transmission is called horizontal transmission, whereas the transmission to new individuals through a gamete is called vertical transmission. The ability of some transposons for horizontal transmission blurs the line between retroviruses and retrotransposons, and indeed in many cases no such line is readily discernable. This means that to some extent many retrotransposons evolve as an independent organism and to some extent as a genetic element imbedded with the genome of the host. The most dramatic cases of horizontal transmission are those in which a transposable element infects individuals from a different species. Interspecific horizontal transmission can be detected by constructing the molecular phylogeny of a transposon sequence found in many different species and comparing it to the molecular phylogeny of some single-copy gene from the same species. If all transposon transmission is vertical, then the two phylogenies should be the same. Horizontal transmission will create topological incongruence between the two phylogenies. Such topological incongruence is shown in Figure 13.5 for the P-element transposon found in several species of Drosophila. The topological incongruence shown in that figure requires a minimum of 11 horizontal transfer events among the 18 species surveyed.

Once a transposon has invaded a new species via horizontal transmission, it can rapidly spread through vertical transmission, particularly if the species has a population structure characterized by a random or outbreeding system of mating and much gene flow. For example, prior to 1949, P elements were generally not found in strains of D. melanogaster collected throughout the world (Anxolabehere et al. 1988). Starting in the 1950s, a few strains collected in the Americas and in the Pacific and Australia began to have P elements (Table 13.4). Over time, the incidence of strains bearing P elements tended to increase in these geographical areas, and moreover P elements spread to populations in Europe, Asia, and Africa. Thus, after the initial horizontal transfer around 1950, it took only about 20 years for P elements to spread throughout D. melanogaster on a global basis.

Drosophila phylogeny

Drosophila phylogeny

D. dacunhai D. sturtevanti D. emaginalis D. subsaltans D. saltans D lusaltnas D. austrosaltans-D. prosaltans D. neocordata D. nebulosa D. fumipennis D. insularis D. paulistorum D. pavlovskiana D. equinoxialis D. willistoni D. tropicalis-D. capricorni D. sucinea S. pallida S. elmoi

P-element phylogeny

Dsubsa29 Dsalt28

Dlusal

Dfumi3

Dfumi2

Daustr

Dfumi9

Dfumi5

Dprosa

Dnebu

Dpauli10

Dpavlo21

Dpauli9

Ppavlo15

Dpauli5

Dpauli15

Dpauli3

Dpavlo16

Dpauli13 Dpauli4

Dequi Dwilli ^ Dtrop ♦^Dcapri ^Dsuci iSpallida18 Spallida02 iSelmoi4 lSelmoi12

P-element phylogeny

Figure 13.5. Comparison of Drosophila species and P-element phylogenetic histories. Double-headed arrows unite P-element clades with the Drosophila species from which they were sampled. Modified from Fig. 4 in J. C. Silva and M. G. Kidwell, Molecular Biology and Evolution 17: 1542-1557 (2000). Copyright © 2000 by Oxford University Press.

By escaping the constraints of gametic transmission, some transposable elements have acquired a remarkable strategy for evolutionary success. However, their evolution as an independent infectious agent still interacts with targets of selection at and below the level of individuals after horizontal transfer has occurred. These multiple levels of selection are not mutually exclusive but rather are interactive in how they shape the response of these remarkable and highly successful units of selection.

Table 13.4. Number and Percentage* of Tested Strains Collected in Four Major Geographical Regions during Five Time Periods without (Pneg) and with (P) P Elements

Americas Europe and Asia Africa Orient and Australia

Table 13.4. Number and Percentage* of Tested Strains Collected in Four Major Geographical Regions during Five Time Periods without (Pneg) and with (P) P Elements

Americas Europe and Asia Africa Orient and Australia

Period

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