14.6: Transposons- moving DNA within a genome (and weird genetics)

As we are thinking about DNA molecules moving into the genome through horizontal (lateral) gene transfer, and between genomes through conjugation, we can consider another widely important molecular system known as transposable elements or transposons. A transposon is a piece of DNA that can move (jump) from place to place in the genome.^[494] The Nobel prize winner Barbara McClintock (1902–1992)(→) first identified transposons while studying maize (Zea mays).^[495] In particular, she studied the phenomena known as variegation in the pigmentation of kernels (→). The variegation phenotype is due to what are known as unstable alleles; these are pairs of alleles in which one allele is associated with one phenotype (e.g. dark pigment) and the other allele is associated with a second phenotype (e.g. different or lighter color). During development of the kernel an allele can change from one state to another. Since tissues are built from (asexual) clones of somatic cells, the earlier in development an allele change occurs, the larger the region associated with its phenotype in the adult organism.^[496]

Transposons can have a number of different effects on the expression of the genes in which they are found.^[497]For example, some transposons can disrupt a gene's coding region. When spliced out of the mRNA the gene can produce a normally functioning gene product.^[498] Alternatively, the insertion of a transposon can inactivate the gene. Transposons come in two general types - those that move a DNA sequence from one place in the genome to another with no increase in total transposon copy number – these are known, for historical reasons, as type II transposons (next ↓ page). Type II transposons come in two forms, known as autonomous and non-autonomous. Autonomous transposons encode a protein known as transposase. The transposon contains repeated nucleotide sequences at each end. Transposase recognizes these repeat sequences and catalyzes the removal of the DNA region between the two repeat sequences and its subsequent insertion into another genomic site. The new site can be located anywhere in the genome where the chromatin is in an "open" (accessible) state. This property has been used to map the regions of the genome that are open, a method known as "Assay for Transposase Accessible Chromatin with high-throughput sequencing" (ATAC-seq).^[499] In non-autonomous type II transposons, mutations have led to the loss of a functional transposase gene within the transposon. By itself, such a transposon cannot move, but if a autonomous transposon becomes active within the cell then the transposase it encodes can catalyze the excision and insertion of a dependent transposons. Why? because the transposase protein is synthesized in the cytoplasm and after it enters the nucleus, it can interact with multiple transposons.

The second type of transposon, known as a type I transposon, is also a DNA sequence but it uses a different mechanism to move. Type I transposons also come in autonomous and non-autonomous forms (↓). The autonomous form encodes a protein known as reverse transcriptase, a RNA-directed, DNA polymerase. When expressed, the type I transposon leads to the generation of an mRNA that encodes reverse transcriptase. Reverse transcriptase can recognize and make a complementary DNA (cDNA) copy of the transposon-encoded RNA. The cDNA can, in turn, be used as the template to generate a double-stranded DNA molecule that can be inserted, more or less randomly, into the genome. In contrast to a type II transposon, the original transposon’s DNA sequence remains in place, and a new transposable element is created and inserted into the genome. If the transposon sequence is inserted into a gene, it may generate a mutation by disrupting the gene’s regulatory or coding sequences. It can also act as a regulatory element, leading to changes in when and where the gene is expressed. In dependent (non-autonomous) type I transposons, mutations have render the reverse transcriptase non-functional; it can only make copies of itself if another, separate autonomous type I transposon is present and actively expressed in the cell.

Transposons do not normally encode essential functions. Random mutations can "kill" a transposon by modifying the molecular features involved in its recognition, excision, replication, and insertion within a genome. If you remember back to our initial discussion of DNA, human and many other types of genomes contain multiple copies of specific sequences - many of these are derived from once active transposons; most are now “dead” – they are the remains of molecular parasites. About ~50% or more of the human genome consists of dead transposons. In particular the human genome contains ~1,000,000 copies of the Alu type transposon (~11% of the total genome); these are dependent, type I transposons that rely on the presence of autonomous transposons to move.^[500] It is probably not surprising then that there can be movement within the genome of specific cells during an organism’s life time, since some transposons are still active.^[501] Moreover, since transposon movement is generally stochastic, as populations separate from one another, the patterns of transposons within the genome diverge from that of the ancestral population.^[502] In addition, various stresses within an organism can enhance transposon movement, which may play a role in the generation of genetic variation - a primary driver of evolutionary diversity and adaptation.^[503]

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