Alu taketh but ERV giveth back.

Sometimes I am asked whether a pseudogene can regain function. The answer, according to a paper by Bekpen et al. (2009), is yes. And the mechanism is cool — an Alu insertion knocked it out and an ERV insertion restored its function.

Author summary

The IRG gene family plays an important role in defense against intracellular bacteria, and genome-wide association studies have implicated structural variants of the single-copy human IRGM locus as a risk factor for Crohn’s disease. We reconstruct the evolutionary history of this region among primates and show that the ancestral tandem gene family contracted to a single pseudogene within the ancestral lineage of apes and monkeys. Phylogenetic analyses support a model where the gene has been “dead” for at least 25 million years of human primate evolution but whose ORF became restored in all human and great ape lineages. We suggest that the rebirth or restoration of the gene coincided with the insertion of an endogenous retrovirus, which now serves as the functional promoter driving human gene expression. We suggest that either the gene is not functional in humans or this represents one of the first documented examples of gene death and rebirth.

This story has already been reported by others, so I will just post links:

The death and resurrection of IRGM – the “Jesus gene” (Not Exactly Rocket Science)

First ‘resurrected’ gene found in humans (New Scientist)

The resurrection of a disease-linked gene (Nature News)

A Curious Case of Genetic Resurrection (ScienceNOW)

(Please don’t get into the whole “aha — scientists shoulnd’t have dismissed Alu and ERVs as junk” trap — see the quotes of interest series).

Update from Africa.

Many regular readers of this blog may recall that my parents were planning to move to Zambia to launch a musical theatre program aimed at providing employment for local artists and generating revenue for the local community. Well, they’ve been there for a few months now, and a lot is going on. You can check it out at my father’s blog if you are in the mood to be inspired.

Today’s post: Water.

Scitable (and a weird piece on DNA barcoding).

I received an email about Scitable, a new online resource by Nature Education. I notice that they have a link to my 2005 paper in Nature Reviews Genetics. Overall, I think the site looks interesting. On a more curious note, I was checking out the material about comparative genomics, and came across this, um, bizarre discussion of DNA barcoding:

[Excerpt from Genomes of Other Organisms: DNA Barcoding and Metagenomics]

Partial Gene Sequences

The method of comparative genomics can be applied not just to full genome sequences, but also to single genes and gene fragments to study their function and help establish relationships among species. Indeed, a species‘ place on an evolutionary tree is a valuable predictor of the structure and function of neighboring taxa.

The current convention of describing (defining) organisms new to science and establishing their evolutionary relationships is based on total evidence; in other words, the organisms’ genetic, morphological, and ecological characters are described and analyzed against other sets of data. Taken together, these techniques can be very informative, having thus far provided us with a detailed road map of Earth’s biota. But for systematics – the study of biological diversity and common ancestry – rapid technological advances in the field of comparative genomics are both a blessing and a curse. Consider, for example, the technique called DNA bar coding, which is based on using short fragments of mitochondrial gene CO1 to uniquely identify and document animal species (Savolainen, 2005). This technique has applications across all living organisms, but the precise genetic methodology is still being developed. In addition, the debate among scientists regarding the use and the utility of DNA bar coding has been quite vociferous. On one hand, this technique brings the promise of instant species identification to a much wider community with minimal biological training. Indeed, it is hypothetically possible to carry a hand-held device out in the field and input species sequences into a rapidly expanding database; all for a fraction of the price, knowledge, and effort associated with the conventional manual method or with human-curated taxonomic identification. So what’s the catch?

One major problem with DNA bar coding is that it operates on the assumption that species have evolved in perfect percentile distances of genetic diversion. Thus, with this technique, in order for any two organisms to be deemed the same species, they must share 88-98% of genetic code at the chosen CO1 mitochondrial gene fragment (Savolainen, 2005). The exact suggested threshold has to be characterized for each group, and neither the threshold nor the groups have been clearly defined for most taxa. Thus, DNA bar coding has been called a “quick fix” and an oversimplification of systematics. Indeed, wide variation in the CO1 gene is found not only among species, but also within them, and even between the cells of an individual organism – a phenomenon known as mitochondrial heteroplasmy (Kmiec & Woloszynska, 2006). Furthermore, there is a broad overlap of inter- and intraspecific genetic distances among closely related species (Goldstein et al., 2000).

These issues come into focus when you consider the devastating malaria epidemic that kills one to three million people worldwide every year. The pathogens that cause malaria are protozoan parasites from the genus Plasmodium that are transmitted through the bite of mosquitoes of the genus Anopheles. Both of these animal genera contain hundreds of species, although only a few are involved in transmitting malaria in humans. Recent genetic studies of the symbiotic bacteria in the midgut of the Anopheles stephensi mosquitoes have yielded promising results: Enterobacter agglomerans bacteria were genetically engineered to display two anti-Plasmodium effector molecules that kill the parasite before it is transmitted to humans (Riehle et al., 2007). Now consider the genetic and physiological differences between the wild-type and genetically modified Anopheles stephensi mosquitoes: they are still the same species by all major standards of species definition, yet what a difference it would make for humankind if the Plasmodium-resistant genetically modified strain were dominant. This example highlights the importance of studying genomes and biological associations of the narrowest niches of life. It also underlines the vital potential for the unpredictable outcomes of genome sequencing-major advances are often made using information generated for completely unrelated reasons.

Ok. The last paragraph has nothing to do with DNA barcoding. As to the critique of DNA barcodes, I find it odd that the author a) does not cite any papers by people who do DNA barcoding, and b) cites a paper from 2000 (i.e., 3 years before DNA barcoding began) as showing that sequences overlap. Nevermind that the paper a) does not discuss COI data, and b) is co-authored by Rob DeSalle and Alfried Vogler (my two postdoc advisors), neither of whom is against the use of DNA in species identifications (though both would prefer cladistic methodology).

The bias is obvious, but at least they could have included some proper references (goodness knows there are enough vocal opponents).

Speaking of small genomes…

… our paper on megabats was published online yesterday. It’s free to access at the moment. Turns out megas have even more constrained genomes than microbats.

Abstract

It has long been recognized that bats and birds contain less DNA in their genomes than their non-flying relatives. It has been suggested that this relates to the high metabolic demands of powered flight, a notion that is supported by the fact that pterosaurs also appear to have exhibited small genomes. Given the long-standing interest in this question, it is surprising that almost no data have been presented regarding genome size diversity among megabats (family Pteropodidae). The present study provides genome size estimates for 43 species of megabats in an effort to fill this gap and to test the hypothesis that all bats, and not just microbats, possess small genomes. Intriguingly, megabats appear to be even more constrained in terms of genome size than the members of other bat families.

With genomes, bigger may really be better…

…as targets for genome sequencing in order to avoid bias in what we discover about gene regulation from sequenced genomes, because so far only small genomes have been sequenced. Such is the message reported at the HHMI based on a recent paper by Michael Eisen. I have written about the major problem of drawing broad conclusions from the biased sequenced genome dataset, and I am very excited to see someone else noting that we really need to examine more diversity. I have been meaning to write a paper on why we need large-scale genome size surveys and why sequencing people should be enthusiastic about it (maybe even help fund it). Here is another great reason that I will cite.

It so happens that a student in my lab will soon be initiating a project on dipteran genome sizes — this gives it even broader significance. I might point out that tephritids do not have “big genomes” for insects by my reckoning (for that, you would need to get beyond holometabolous orders). Finally, if you’re wondering why Drosophila genomes are so streamlined, it actually looks like development may constrain how large they can be.

My favourite PhD comics.

Stephen Jay Gould once noted that The Far Side by Gary Larson adorns more scientists’ office doors than any other series of cartoons. This was certainly true a number of years ago, but I think that honour may have passed to a new generation. In particular, Piled Higher and Deeper by Jorge Cham (PhD) is now to be found not only on faculty doors but on a large percentage of graduate student office doors as well. (I even bought copies of the books to keep in my lab).

Here are some of my personal favourites: