In this article we will discuss about transposable elements in human.
In human genome, two retro-transposons called LINEs (long interspersed sequences) and SINEs (short interspersed sequences) are found. LINEs are repeated sequences more than 5,000 bp long, interspersed among unique sequence DNA up to approximately 35,000 bp long. Full length LINEs are autonomous elements that encode the enzymes for their own retro-transposition and enzymes required for the transposition of SINEs.
SINEs are 100-400 bp repeated sequences interspersed between unique sequence DNA 1,000 to 2,000 bp long. SINEs are non-autonomous elements. Therefore, they depend upon the enzymes coded by LINEs for their transposition. In humans, a very abundant SINE family is the Alu family. It contains the repeated sequence of about 300 bp long which is repeated 300,000 to 500,000 times in the genome.
It ampunts up to 3 percent of the total genomic DNA. It contains the enzyme Alu 1 (A1 you one). The Alu sequence can transpose as evidenced from the study with patients of neurofibromatosis. DNA analysis of these patients showed that an Alu sequence was present in one of the introns of the neurofibromatosis gene.
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The RNA transcript of this gene was longer than those from normal individuals. The Alu sequence present in the intron disrupted the processing of the transcript, causing one exon to be lost completely from the mature mRNA. As a result the protein coded was 800 amino acids shorter than normal and was nonfunctional.
It was found that individual members of Alu family are not identical in sequence, so have diverged over evolutionary time. This divergence may cause to track down the same Alu sequence in the patient’s parents which were found to be normal. Thus, the Alu sequence probably inserts into the neurofibromatosis gene by retro-transposition in the germ line of the father.
In human genome the best studied LINE is L1 which is about 6,500 bp long. Many L1 elements may have internal deletions of various lengths. The full length L1 contains a large open reading frame that is homologous to known reverse transcriptases. L1 and other LINEs do not have LTRs. Thus, they are not closely related to the retro-transposons.
It was shown, that insertions of an L1 element into the factor VIII gene resulted in haemophilia in two unrelated children. Insertion was not present in either of their parents. So it was concluded that L1 element had newly transposed and L1 element can cause disease by inserting into genes, a process called insertional mutagenesis.
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Importance of Transposable Elements in Evolution:
Only a couple of decades ago, molecular biologists considered the genome to be a stable repository of genetic information. Now it is established that organisms can maintain their genome from one day to the next in the face of large-scale disruption by genetic rearrangement. However, there is a continuous debate regarding actual role of transposons in organic evolution.
One group thinks that transposable elements have no function; rather, these are a type of “genetic parasite” that can spread within the host genome. These can be transmitted to the next generations as long as they do not have important adverse effects on the ability of the host to survive and reproduce. The other group argues that transposons are key element to cause genomic changes that fuel the biological evolution.
Studies of the genomes of various mammals indicate that the Alu sequence first appeared as a transposable element in the genome of higher primates about 60 million years ago. Ever since, it has been increasing in copy number at the rate of about one copy every 100 years.
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It was found that the average Alu family member has been in the genome of human evolutionary line for about 25 million years. This sequence does not repeat in genomes throughout the animal kingdom. However, whether its amplification is reaching a saturation point in these genome or is continuing unimpeded, cannot be determined with the present day data.
But it is clear, the movement of a transposon has a deleterious effect on the expression of a gene in the target DNA. In rare occasions, such movement might be expected to be beneficial, providing the organism with a selective advantage. Broadly, it is suggested that transposons may cause the appearance of new species.
It has had a major impact on altering the genetic composition of organisms as they evolve. This idea was evidenced by the P elements of Drosophila. Flies descended from individuals trapped by T. H. Morgan and his co-workers were devoid of P element at the start of the century. But every member of the species caught in ‘wild’, today carries this transposons.
Thus, it is thought that P elements have been introduced into the genome of a single fruit fly within the past fifty years or so, probably via transposition from a fly of another species and has rapidly spread through the entire fruit fly population.