The Alu in You

Jared* concludes his stint of posting at BCC. Earlier posts here, here, here, and here.

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.

So what?

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.

See also my previous posts, Mobile Genetic Elements and Animal Relationships and Understanding Trichotomy.

Comments

  1. Jared*, this is very cool. I’ve never heard of Alu elements before, so thank you for explaining this in a way that I can understand. And thanks for your other posts as well.

  2. Ditto. Cool stuff.

  3. Eric Russell says:

    “support the conclusion that humans are genetically related to other primates by common descent.”

    But what really matters is whether this is agreed upon by common consent.

  4. “Any competing hypothesis must make sense of the lowly Alu.”

    I like the way you frame the ‘dilemma'; now let’s see if anyone takes you up on it….

  5. Thanks for the up-to-date analysis. Here’s another one from yesterday’s Deseret Morning News article “Scientists slightly widen our tiny DNA gap.” It was previously estimated that humans and chimps were 99 percent similar. Now that figure is 95 percent.

    Don’t get me wrong. The similarity (whatever the percent) between humans and chimps does not confirm a common ancestor, it confirms “the sovereignty of physical laws.” (Packer, “The Law and the Light.”)

    If the estimate can change once, it will change again. Without revelation, we just don’t know what happened in the distant past.

  6. Why no Alu elements in non-primates?

  7. Are the Alu elements named for the noise Tigger makes in the 100 Acre woods when he’s lost or stuck in a tree?

  8. John, #6: Alu’s are only one type of mobile element. Other types of mobile elements exist in non-primates.

  9. Alu elements appear to be derived from duplication of the 7SL RNA gene, which is part of the ribosome complex. It is explained here. They are limited to primates presumably because the chance events that led to their creation occurred–or were completed–in early primates.

    Mice have a similar SINE that is also derived from the 7SL RNA.

  10. Alu elements, and other similar genomic elements represent a strong challenge to the “similar DNA = similar engineering” argument against common descent. Among other things, that argument implies that each shared element across species was purposefully put there in a nested hierarchy that happens to match evolutionary relationships determined by other means.

    It’s like saying that the various blotches and lines that appear as documents are photocopied over and over are there for intentional reasons. You’ve got to show why it was necessary that some copies have matching coffee stains, but not others.

  11. You say that ALUs are only in primates? That they seem to make random insertions?

    I have been wondering why the genus homo has evolved so fast. I have often thought that there should be a mechanism by which random mutations are made at a much higher rate than produced by natural means such as cosmic rays and thermal excitations. So ALUs and the like are that mechanism.

  12. I would think that the mechanisms that enforce faithful DNA replication are the thing to marvel at more than the fact that transcription errors sometimes creep in.

  13. In order to have a high rate of evolution, DNA changes must occur. The genus homo and related great apes have a very rapid evolutionary history. In just a few million years or so we have come from Lucy to us. In 10 million years from prototypical ancestor, very apelike, to a very sophisticated descendant.

    My question has always been, where have the genotype changes necessary for this phenotype evolution come from? Here is a mechanism which makes for messy progress by introducing changes. Most of the changes will be deleterious, but some will be “progressive” in some way, fostering survival and breeding.

    The other mechanism for faster evolution has been the ability of intelligent selection. As our ancestors became more sophisticated, the choice of mates came under intelligent control. That allowed for faster removal of unsuccessful traits.

    I mean, the dinosaurs spent 150 million years as masters of the planet but showed scant progress in the direction of understanding and sophistication of thought. Compare this to the mere 10 million years for our decent from an unsophisticated predecessor. This is a 15 fold acceleration.

    Of course the situation is always more complex than a short explanation. And, I agree with John (12), the whole thing is a marvel.

  14. BobW,

    Mutation is often thought of as single nucleotide changes. However, there are other mechanisms including deletions, duplications, insertion of mobile elements, recombination, and exon shuffling. There is still a lot of work to be done to understand how mutation maps to development and evolution. Some people think that the regulation of genes is more important than the genes themselves. Others aren’t so sure. And let’s not forget about neuroscience, which I know very little about.

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