Copy Number Variants are not evidence of design

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The Institute for Creation Research has a charming little magazine called “Acts & Facts” that prints examples of their “research” — which usually means misreading some scientific paper and distorting it to make a fallacious case for a literal interpretation of the bible. Here’s a classic example: Chimps and People Show ‘Architectural’ Genetic Design, by Brian Thomas, M.S. (Note: this is not the peer-reviewed research paper implied by the logo to the left — that comes later.) The paper is a weird gloss on recent work on CNVs, or copy number variants. Mr Thomas makes a standard creationist inference that I have to hold up for public ridicule.

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My human lineage

This is a very simple, lucid video of Spencer Wells talking about his work on the Genographic Project, the effort to accumulate lots of individual genetic data to map out where we all came from.

I’ve also submitted a test tube full of cheek epithelial cells to this project, and Lynn Fellman is going to be doing a DNA portrait of me. I had my Y chromosome analyzed just because my paternal ancestry was a bit murky and messy and potentially more surprising, and my mother’s family was many generations of stay-at-home Scandinavian peasantry, so I knew what to expect there. Dad turned out to be not such a great surprise, either. I have the single nucleotide polymorphism M343, which puts me in the R1b haplogroup, which is just the most common Y haplogroup in western Europe. I share a Y chromosome with a great many other fellows from England, France, the Netherlands, etc., which is where the anecdotal family history suggested we were from (family legend has it that the first American Myers in my line was a 17th or 18th century immigrant from the Netherlands). Here’s a map of where the older members of my lineage have been from: Africa (of course!) by way of a long detour through central Asia.

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Hello, many-times-great-grandpa! That’s quite the long walk your family has taken. Howdy, great big extended family! We’ll have to get together sometime and keep in touch.

If you’re interested in finding out what clump of humanity you belong to, it’s easy: you can order a $100 kit, swab out a few cheek cells (just like they do on CSI or Law & Order!), mail it back, and a few weeks later, they send you your results. It’s not very detailed — they only analyze a small number of markers — but it’s enough to get a rough picture of where your branch of the family tree lies. And for a bit more, Lynn can turn it into something lovely for your wall.

By the way, Lynn and I will be talking about the science and art of human genetics in a Cafe Scientifique session in Minneapolis in February.

Epigenetics

Blogging on Peer-Reviewed Research

Epigenetics is the study of heritable traits that are not dependent on the primary sequence of DNA. That’s a short, simple definition, and it’s also largely unsatisfactory. For one, the inclusion of the word “heritable” excludes some significant players — the differentiation of neurons requires major epigenetic shaping, but these cells have undergone a terminal division and will never divide again — but at the same time, the heritability of traits that aren’t defined by the primary sequence is probably the first thing that comes to mind in any discussion of epigenetics. Another problem is the vague, open-endedness of the definition: it basically includes everything. Gene regulation, physiological adaptation, disease responses…they all fall into the catch-all of epigenetics.

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Evolgen disputes my explanation!

RPM of Evolgen disagrees with my definition of synteny! This is terribly distressing. Especially since, strictly speaking, he is precisely correct. The word has evolved in its usage from the pure form that RPM is describing to a more colloquial, pragmatic, somewhat sloppier sense as used by people looking at comparative genomics rather than classical Drosophila genetics.

If you read contemporary evo-devo papers, my definition is more useful in comprehending what they’re saying. If you want to read Drosophila genetics papers, you better know what RPM is talking about, or god help you (and there is no god).

Amphioxus and the evolution of the chordate genome

Blogging on Peer-Reviewed Research

This is an amphioxus, a cephalochordate or lancelet. It’s been stained to increase contrast; in life, they are pale, almost transparent.

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It looks rather fish-like, or rather, much like a larval fish, with it’s repeated blocks of muscle arranged along a stream-lined form, and a notochord, or elastic rod that forms a central axis for efficient lateral motion of the tail…and it has a true tail that extends beyond the anus. Look closely at the front end, though: this is no vertebrate.

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It’s not much of a head. The notochord extends all the way to the front of the animal (in us vertebrates, it only reaches up as far as the base of the hindbrain); there’s no obvious brain, only the continuation of the spinal cord; there isn’t even a face, just an open hole fringed with tentacles. This animal collects small microorganisms in coastal waters, gulping them down and passing them back to the gill slits, which aren’t actually part of gills, but are components of a branchial net that allows water to filter through while trapping food particles. It’s a good living — they lounge about in large numbers on tropical beaches, sucking down liquids and any passing food, much like American tourists.

These animals have fascinated biologists for well over a century. They seem so primitive, with a mixture of features that are clearly similar to those of modern vertebrates, yet at the same time lacking significant elements. Could they be relics of the ancestral chordate condition? A new paper is out that discusses in detail the structure of the amphioxus genome, which reveals unifying elements that tell us much about the last common ancestor of all chordates.

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Basics: Synteny

Let’s play the most boring card game in the universe!

Here are the rules. We start with a fully sorted deck of 52 cards, and we deal out four hands. We don’t deal in the ordinary way, either: we give the top 13 cards to the first player, then the next 13 to the second, and so forth. (We could also do the usual deal, but it makes the illustration and logic a little more difficult to see. We’ll keep it simple for now.)

This is what the table will look like.

Hand 1 Ai-233f23e2a2ca8059264849e39e1760d2-heart.gif Ki-233f23e2a2ca8059264849e39e1760d2-heart.gif Qi-233f23e2a2ca8059264849e39e1760d2-heart.gif Ji-233f23e2a2ca8059264849e39e1760d2-heart.gif 10i-233f23e2a2ca8059264849e39e1760d2-heart.gif 9i-233f23e2a2ca8059264849e39e1760d2-heart.gif 8i-233f23e2a2ca8059264849e39e1760d2-heart.gif 7i-233f23e2a2ca8059264849e39e1760d2-heart.gif 6i-233f23e2a2ca8059264849e39e1760d2-heart.gif 5i-233f23e2a2ca8059264849e39e1760d2-heart.gif 4i-233f23e2a2ca8059264849e39e1760d2-heart.gif 3i-233f23e2a2ca8059264849e39e1760d2-heart.gif 2i-233f23e2a2ca8059264849e39e1760d2-heart.gif
Hand 2 Ai-94f8cf214b78029e2cd1e9398229dda0-club.gif Ki-94f8cf214b78029e2cd1e9398229dda0-club.gif Qi-94f8cf214b78029e2cd1e9398229dda0-club.gif Ji-94f8cf214b78029e2cd1e9398229dda0-club.gif 10i-94f8cf214b78029e2cd1e9398229dda0-club.gif 9i-94f8cf214b78029e2cd1e9398229dda0-club.gif 8i-94f8cf214b78029e2cd1e9398229dda0-club.gif 7i-94f8cf214b78029e2cd1e9398229dda0-club.gif 6i-94f8cf214b78029e2cd1e9398229dda0-club.gif 5i-94f8cf214b78029e2cd1e9398229dda0-club.gif 4i-94f8cf214b78029e2cd1e9398229dda0-club.gif 3i-94f8cf214b78029e2cd1e9398229dda0-club.gif 2i-94f8cf214b78029e2cd1e9398229dda0-club.gif
Hand 3 Ai-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif Ki-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif Qi-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif Ji-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 10i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 9i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 8i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 7i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 6i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 5i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 4i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 3i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 2i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif
Hand 4 Ai-37cc42c4042ea4372806e327e67b2e42-spade.gif Ki-37cc42c4042ea4372806e327e67b2e42-spade.gif Qi-37cc42c4042ea4372806e327e67b2e42-spade.gif Ji-37cc42c4042ea4372806e327e67b2e42-spade.gif 10i-37cc42c4042ea4372806e327e67b2e42-spade.gif 9i-37cc42c4042ea4372806e327e67b2e42-spade.gif 8i-37cc42c4042ea4372806e327e67b2e42-spade.gif 7i-37cc42c4042ea4372806e327e67b2e42-spade.gif 6i-37cc42c4042ea4372806e327e67b2e42-spade.gif 5i-37cc42c4042ea4372806e327e67b2e42-spade.gif 4i-37cc42c4042ea4372806e327e67b2e42-spade.gif 3i-37cc42c4042ea4372806e327e67b2e42-spade.gif 2i-37cc42c4042ea4372806e327e67b2e42-spade.gif

Next, we play the game, whatever it is. It really doesn’t matter, since we know exactly what hand everyone has, right? So don’t worry about the rules for that. What’s important is that next the dealer carefully picks up each hand in reverse order and stacks them, restoring the original arrangement of the deck.

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The platypus genome

Blogging on Peer-Reviewed Research

Finals week is upon me, and I should be working on piles of paper work right now, but I need a break … and I have to vent some frustration with the popular press coverage of an important scientific event this week, the publication of a draft of the platypus genome. Over and over again, the newspaper lead is that the platypus is “weird” or “odd” or worse, they imply that the animal is a chimera — “the egg-laying critter is a genetic potpourri — part bird, part reptile and part lactating mammal”. No, no, no, a thousand times no; this is the wrong message. The platypus is not part bird, as birds are an independent and (directly) unrelated lineage; you can say it is part reptile, but that is because it is a member of a great reptilian clade that includes prototherians, marsupials, birds, lizards and snakes, dinosaurs, and us eutherian mammals. We can say with equal justification that we are part reptile, too. What’s interesting about the platypus is that it belongs to a lineage that separated from ours approximately 166 million years ago, deep in the Mesozoic, and it has independently lost different elements of our last common ancestor, and by comparing bits, we can get a clearer picture of what the Jurassic mammals were like, and what we contemporary mammals have gained and lost genetically over the course of evolution.

We can see that the journalistic convention of emphasizing the platypus as an odd duck of a composite creature is missing the whole point if we just look at the title of the paper: “Genome analysis of the platypus reveals unique signatures of evolution.” This is work that is describing the evidence for evolution in a comparative analysis of the genomes of multiple organisms, with emphasis on the newly revealed data from the platypus.

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Squish

That’s the sound you should hear when Joe Felsenstein takes on an idiotic claim by Sal Cordova. Would you believe that Cordova claims that Kimura and Ohta’s classic 1971 paper “shatters the modern synthesis”? That’s what he claims, on the basis of his poor understanding of the mathematics of population genetics, which is ridiculous on the face of it. So it’s very satisfying to see one of the big guns of population genetics take him down with one brief explanation: contrary to Cordova, the principle he’s describing confirms the effectiveness of natural selection.


Just to help everyone follow along, here’s the simple explanation. As Kimura and Ohta explained, most mutations, even advantageous ones, do not go to fixation in a population, and are lost. Slimy Sal just reports only that much, and declares the end of evolution, to huzzahs from his equally ignorant cronies. What he ignores, and what Felsenstein explains, is that 1) the frequency of fixation of advantageous alleles will be much, much greater than for neutral or deleterious alleles, and 2) that there are many mutations being generated — so natural selection is an effective filter.

It’s a kind of mathematical quote mine, where Cordova only tells a tiny part of the story and leaves out the important bit that destroys his thesis.

Basics: How can chromosome numbers change?

There in the foaming welter of email constantly flooding my in-box was an actual, real, good, sincere question from someone who didn’t understand how chromosome numbers could change over time — and he also asked with enough detail that I could actually see where his thinking was going awry. This is great! How could I not take time to answer?

So here’s the question:

How did life evolve from one (I suspect) chromosome to… 64 in horses, or whatever organism you want to pick. How is it possible for a sexually reproducing population of organisms to change chromosome numbers over time?

Firstly: there would have to be some benefit to the replication probability of the organisms which carry the chromosomes. I don’t see how this would work. How is having more chromosomes of any extra benefit to an organism’s replicative success? Yes, perhaps if those chromosomes were full of useful information… but the chances of that happening are non existent and fly in the face of ‘small adaptations over time’.

Secondly, the extra chromosomes need to come from somewhere. I’m not sure about this, but I believe chromosome number are not determined by genes, are they? There isn’t a set of genes which determines the number of chromosomes an organism has. So the number is fixed, determined by the sexually reproducing parents. Which leads me to believe that if the number does change, and by chance the organism is still alive and capable of sexual reproduction, that the number will start swinging back and forward, by 1 or 2, every generation, and never stabilising. The chances of this happening are also very very slim.

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A neurological mechanism for Fragile-X disease

Blogging on Peer-Reviewed Research
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I’m busy preparing my lecture for genetics this morning, in which I’m going to be talking about some chromosomal disorders … and I noticed that this summary of Fragile-X syndrome that was on the old site hadn’t made it over here yet. A lot of the science stuff here actually gets used in my lectures, so they represent a kind of scattered online notes, so I figured I’d better put this one where I can find it.


I haven’t even finished grading the last of the developmental biology papers, and already my brain is swiveling towards the genetics literature, as I get in the right frame of mind to teach our core genetics course in the spring. And, lo, here is a new paper in PNAS that addresses details of a topic I bring up every time.

There are a surprising number of heritable diseases that share a couple of common traits: they are neurodegenerative, causing progressive loss of neural control, and they also exhibit a phenomenon called genetic anticipation—they tend to get worse, with earlier onset and more severe affects with each generation. Some of these diseases may be rather obscure, for instance
Haw-River Syndrome (AKA Dentatorubral-pallidoluysian atrophy),
Friedreich Ataxia,
Machado-Joseph Disease, or
X-linked Spinal and Bulbar Atrophy Disease (AKA Kennedy Disease), but others you’ve probably heard of, like
Myotonic dystrophy and
Huntington Disease. These are dreadful diseases that are variable in their pattern of appearance, and have terrible symptoms, like loss of motor control, chorea, seizures, dementia, and eventually, death.

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