Alu need to know about parasitic DNA: Alu elements and blindness

Age-related macular degeneration (AMD) is a leading cause of blindness in humans, and the leading cause of visual impairment during advanced age. The condition comes in two basic forms, the most severe of which is untreatable. Called geographic atrophy (GA), this condition involves the steady destruction of the retinal pigment epithelium, a layer of tissue in the eye that is essential for the health and maintenance of the photoreceptors in the retina. Loss of the pigment epithelium means certain death for the photoreceptors, and that means visual impairment and then blindness for the affected person.

A major publication in Nature last month (Kaneko et al., "DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration," Nature 17 March 2011) now points to one likely cause of AMD, and in the process provides a chilling example of what can happen when the parasitic Alu elements in our genomes (see the previous post for an introduction) are left unrestrained.

Alu need to know about parasitic DNA: Introduction to Alu elements

Defenders of intelligent design theory often dwell on the topic of "junk DNA," which has been molded into a masterpiece of folk science. The ID approach to "junk DNA" involves a fictional story about "Darwinism" discouraging its study, and a contorted and simplistic picture of a "debate" about whether "junk DNA" has "function." The fictional story is ubiquitous despite being repeatedly debunked. But the picture of an ongoing "debate" about "function" is harder to sort out. Like most propaganda, that picture contains enough truth to sound plausible. (Browse my "Junk DNA" posts, and work by Ryan Gregory and Larry Moran, for more information on errors and folk science associated with these topics.)

There is, in fact, some scientific disagreement about functions of various elements in genomes, but it's not the crude standoff that ID apologists depict, and it has very little to do with "Darwinism." The debate, if we must call it that, is about at least two matters: 1) the extent to which certain genomic elements contribute to normal function or development of organisms; and 2) the means by which we might determine this. The debate is not about whether non-coding DNA can have function, or even about whether some segments of non-coding DNA do have function. That debate was invented by anti-evolution propagandists.

34th Carnival of Evolution

Welcome to the 34th Edition (1 April 2011) of the Carnival of Evolution, and welcome to Quintessence of Dust. It's nice to be hosting this fine carnival, and to see that it's still going strong.

I've organized the carnival under some chapter and section headings that I got from some old Victorian's magnum opus, but I think you'll find the topics require no further creative embellishment.

Mapping fitness: protein display, fitness, and Seattle

A couple of months ago we started looking at the concept of fitness landscapes and at some new papers that have significantly expanded our knowledge of the maps of these hypothetical spaces. Recall that a fitness landscape, basically speaking, is a representation of the relative fitness of a biological entity, mapped with respect to some measure of genetic change or diversity. The entity in question could be a protein or an organism or a population, mapped onto specific genetic sequences (a DNA or protein sequence) or onto genetic makeup of whole organisms. The purpose of the map is to depict the effects of genetic variation on fitness.

Suppose we want to examine the fitness landscape represented by the structure of a single protein. Our map would show the fitness of the protein (its function, measured somehow) and how fitness is affected by variations in the structure of the protein (its sequence, varied somehow). It's hard enough to explain or read such a map. Even more daunting is the task of creating a detailed map of such a widely-varying space. Two particular sets of challenges come to mind.

It's just a stage. A phylotypic stage. Part III: Fish and more

Given that disputes over the existence and meaning of the phylotypic stage and the hourglass model have simmered in various forms for a century and a half, the remarkable correspondence between the hourglass model and gene expression divergence discovered by Kalinka and Varga and colleagues would be big news all by itself. But amazingly, that issue of Nature included two distinct reports on the underpinnings of the phylotypic stage. The other article involved work in another venerable model system in genetics, the zebrafish.

The report is titled "A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns" and is co-authored by Tomislav Domazet-Loso and Diethard Tautz. To understand how their work has shed light on the phylotypic stage and the evolution of development, we'll need to look first at an approach to the analysis of evolutionary genetics that these two scientists pioneered: phylostratigraphy.

It's just a stage. A phylotypic stage. Part II: The flies

The controversy about the existence of the phylotypic stage is more than some bickering about whether one blobby, slimy fish-thing looks more like a Roswell alien than another one does. It's about whether the phylotypic stage means something, whether it tells us something important about development and how developmental changes contribute to evolution. To answer such a question, we need more than another set of comparisons of the shape and movements of embryos and their parts. We need a completely different way of looking at the phylotypic stage, to see if something notable is going on under the hood. So vertebrates all look the same at the tailbud stage. What does that mean?

Embryos look the way they do because of the positions and behaviors of the cells that make them up. The cells in an embryo all have the same DNA, and the link between that DNA and those specific cell behaviors is the basic process of gene expression. (This is a fundamental principle of developmental biology.) And by gene expression, we usually mean the synthesis of messenger RNA under the direction of genes in the DNA. Different cell types express different sets of genes, and the orchestration of the expression of particular genes at particular times is a big part of what makes development happen. When considering the phylotypic stage, then, developmental biologists wondered: is the apparent similarity of embryos at that stage reflected by similarities in gene expression. Or, more specifically, does the hourglass model hold up when we look at gene expression? This was the focus of the two articles in last Friday's Nature that inspired the cool cover.

It's just a stage. A phylotypic stage. Part I.

Disputes and controversies in science are always a good thing. They're fun to read about (and to write about), and they're bellwethers of the health of the enterprise. Moreover, they tend to stimulate thought and experimentation. Whether scientists are bickering about evo-devo, or about stem cells in cancer, or about prebiotic chemistry, and whether or not the climate is genial or hostile, the result is valuable.

Now of course, some controversies are invented by demagogues for political purposes. The dispute in such cases is far less interesting and clearly less profitable, even if participation by scientists is necessary.

This week, two papers in Nature weighed in on a major scientific controversy that has its roots in pre-Darwin embryology, fueled by some gigantic scientific personalities and even tinged with what some would call fraud. This intense scientific dispute spawned a sort of doppelganger, a manufactured controversy that is just one more invention of anti-evolution propagandists. The Nature cover story gives us a great opportunity to look into the controversies, real and imagined, and to learn a lot about evolution and development and the things we're still trying to understand about both.

Mapping fitness: bacteria, mutations, and Seattle

Thinking about fitness landscapes can stimulate detailed discussion and consideration of the meanings and limitations of such metaphors, and my introductory comments at The Panda's Thumb did just that. Most notably, Joe Felsenstein pointed us to the various ways these depictions can be employed, and urged everyone to use caution in interpreting them. All too true, but the goal here is modest: I want to discuss the interesting questions that arise when considering the relationship between genotypes and phenotypes, i.e., how a particular genetic makeup influences fitness, whether the genetic makeup in question is simple or complex, and however fitness is conceived. These questions can take further discussion in all sorts of directions, but there are two that I have in mind in this series. First, I want to point to increasing capacity of scientists in their ability to examine these relationships experimentally. Second, I want to highlight the failure of design creationists to address or even to understand such matters.

Mapping fitness: landscapes, topographic maps, and Seattle

The concept of a "fitness landscape" is a fundamental idea in evolutionary biology, first introduced and established during the so-called "evolutionary synthesis" in the early 20^th century. It was the great Sewall Wright who pictured adaptation as a "walk" through a landscape (pictured below), where the walking is done by variants (of an organism or a molecule) and the landscape is a theoretical representation of the relative fitness of the variants. (J.B.S. Haldane did similar work around the same time, but Wright's paper is much better known perhaps because it's more accessible to non-experts. See Carneiro and Hartl in PNAS earlier this year for more.)

It's a simple concept, and a helpful one, though sometimes subject to over-interpretation. And it helps to frame some of the big questions in evolutionary genetics. One of those big questions is this one, stated somewhat simplistically: how do the variants navigate to fitness peaks, if there are fitness valleys that separate the peaks? (The ideas is that fitness is higher on the peaks, and so a population would be unlikely to descend from a local peak into a valley.) In other words, given a particular fitness landscape, what are the evolutionary trajectories by which variation can explore that landscape?

Biologos and Christian unity: mission accomplished?

And so, last week, some of my friends from BioLogos and Calvin College participated in this Vibrant Dance thing. These are people I hold in very high regard, people pursuing goals that I consider to be among the most important projects a Christian scientist can tackle. But mistakes are being made, and in a previous post I pointed to one of the biggest ones: overemphasizing "Christian unity" in an environment of rampant dishonesty, an environment poisoned by apologetic propaganda.