My time is up, but I have enjoyed my stay for the last couple of weeks. The last post for this guest session is more on the educational side, but I hope you like it.
Mobile genetic elements have become a little bit of a hobby-topic for me over the last few years. I am not a expert on them, just an interested observer. In this post I want to introduce you to a certain class of mobile elements called Alu elements. I hope that you will find them interesting too.
What are they?
Alu elements are chunks of DNA that are members of a broader group of elements called short interspersed elements (SINEs). They do not code for any proteins, yet the human genome contains over a million copies of them. This means that, at about 300 base pairs in length, Alu elements make up over 10% of your DNA (with other mobile elements accounting for another 35%). Alu elements spread through the genome by being copied by enzymes produced by other genomic elements. They are transcribed into RNA, which is then copied back into DNA in a process known as reverse transcription. The new DNA copy then inserts somewhere else in the genome. In this respect, Alu elements are a lot like viruses such as HIV. However, Alu elements (as mentioned before) do not code for any proteins of their own, and the new copies never leave the cell. If this process occurs in a germline cell, the new Alu copy can be passed on to posterity like any other piece of DNA. In fact, this does occur at an estimated rate of one new Alu insertion per 200 births, and is sometimes responsible for genetic disease.
What do they do?
That’s kind of like asking what volcanoes do–sometimes they build islands, sometimes they destroy cities, sometimes they just sit there doing nothing. Analogously, Alu elements can cause disease by interrupting or deleting a gene, but they can also alter the regulation of genes or become part of genes themselves. Or they can just sit there and apparently do nothing.
Scientists have found Alu elements to be useful for determining genetic relationships. Since the ancestral state is known to be the lack of an Alu at any particular locus, loci lacking Alu insertions are almost always inferred to be ancestral to those with insertions. The various Alu copies can be grouped into families based on diagnostic mutations, and the chances that two Alu elements of the same family would independently integrate in the exact same position of the genome is considered very low. Therefore, people who share an identical Alu insertion are almost certainly genetically related. Using a handful of polymorphic Alu insertions, scientists have demonstrated the ability to determine the geographic origin of people, and this technique may have forensic application. Population studies using polymorphic Alu insertions support the African origin of humans.
It turns out that Alu elements originated, and are only found, in primates, and they have been used to help clarify relationships on a broader scale. One study (Salem, et al.) looked at the presence of a particular family of Alu elements in several primate species (including humans). Here is a summary of what they found (the numbers on top of each node have to do with statistics; the bottom number represents the number of Alu insertions shared by all species branching from that node):
It’s not all peaches and cream; there are various reasons why an individual Alu insertion can lead one astray. (In fact, the same paper describes a contradictory anomalous finding and explains the likely reason for it.) However, the majority of the Alu evidence obtained thus far is congruent with comparisons of other genomic features and support the conclusion that humans are genetically related to other primates by common descent.
Any competing hypothesis must make sense of the lowly Alu.
References and Further Reading:
1. Batzer MA, Deininger PL. Alu repeats and human genomic diversity. Nat Rev Genet. 2002 May;3(5):370-9.
2. Salem AH, Ray DA, Xing J, Callinan PA, Myers JS, Hedges DJ, Garber RK, Witherspoon DJ, Jorde LB, Batzer MA. Alu elements and hominid phylogenetics. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12787-91. Epub 2003 Oct 15.
3. Ray DA, Walker JA, Hall A, Llewellyn B, Ballantyne J, Christian AT, Turteltaub K, Batzer MA. Inference of human geographic origins using Alu insertion polymorphisms. Forensic Sci Int. 2005 Oct 29;153(2-3):117-24.
One of the leading publishers on Alu elements is Mark Batzer and his lab website makes many of his publications available for free.