SINEs and LINEs

Last week I talked about retrotransposons and ended with a video that briefly discussed SINEs and LINEs. I want to spend this week discussing transposons in a little more detail and mention some of the problems that can arise from these transposable elements.

SINEs, LINEs, and LTRs are all retrotransposons that insert themselves into RNA through the copy and pasting method described last week. SINEs are made up of three different subgroups known as Alu, MIR, and MIR3, which act a little differently from the other two retrotransposon classes (Nelson et al. 2004). Reverse transcriptase doesn't act on SINEs which is necessary for the process of copying and pasting to occur (Nelson et al. 2004). Instead, SINEs must work with LINEs that have a similar 3' end sequence in order to use the activity from them to insert themselves (Nelson et al. 2004). LTRs only appear in humans in 4 different forms, and even in these cases, most of their sequences have been shortened by homologous recombination causing them to be "isolated elements" (Nelson et al. 2004).
Mills et al. (2007) stated that transposons make up about 44% of the human genome, but despite this amount, less than 0.05% of them are actually active. Retrotransposons that are still able to move are of high interest to researchers because their insertion and rearrangement of genetic material can cause differences in phenotypes that may hinder the host organism (Mills et al. 2007). Transposonase tends to favor inactive transposable elements that have deletions or mutations which causes an increase in production of these transposons. Although these transposable elements don't do anything they become more numerous and make up a large part of the genome (Nelson et al. 2004). LINEs are different in the fact that they generally interact with functional RNA which prevents them from losing any function so they can remain active (Nelson et al. 2004). Nelson et al. (2004) explained that transposons become embedded within the open reading frame region of genes through alternative splicing of introns. This causes the sequences to be lengthened or cut short, and if done in certain ways may end with transposable elements in the coding regions of genes that didn't normally have them (Nelson et al. 2004).

Focusing specifically on LINE-1 (L1) and Alu elements, Mills et al. (2007) reported that researchers had trouble finding the active retrotransposons amongst the many inactive ones until diseases linked to them were observed. L1 elements are usually sequences shortened at the 5' end making them difficult to identify within a gene (Mills et al. 2007). As they fit within the normal sequence it is hard to determine where the sequence ends and the inserted retrotransposon begins. Alu elements are controlled by L1 elements so these transposons are even harder to find because you need to be able to locate the L1 element before finding Alu (Mills et al. 2007). In order to determine which retrotransposons are still currently active and which are immobile, researchers compared human and chimpanzee genomes (Mills et al. 2007). They find where a transposon has recently inserted multiple sequences and then determine if the observed retrotransposon is in both genomes or if it is only found in the human genome (Mills et al. 2007). Any retrotransposons found in both genomes are thought to be immobile because it is believed that they became part of the genome before the evolutionary divergence between human and chimps (Mills et al. 2007). Retrotransposons solely in the human genome are thought to be more recently inserted and have a greater chance of activity (Mills et al. 2007). Of these active transposons, L1, Alu, and SVU elements have shown to be most commonly associated with human diseases (Mills et al. 2007).

Many transposable elements are found within the proteins of genes causing differences in the functions and coding of each protein (Nelson et al. 2004). This can lead to altered interactions of genes and ultimately result in a number of diseases depending on which genes are affected. LINEs can interact with mRNA from neighboring genes causing new insertions and the development of pseudogenes in many places within the genome (Nelson et al. 2004). Changes to the sequence of the genome effects the regulation of genes, and any slight change can result in mutagenic activity within the organism (Nelson et al. 2004). Alu retrotransposons have caused mis-pairing and crossing over in genes resulting in many deletions in host organisms (Nelson et al. 2004). The activity of retrotransposons which resulted in alterations to genetic sequences has been associated with a number of diseases such as muscular dystrophy, haemophilia, Huntington's disease, and some forms of breast cancer (Nelson et al. 2004).