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Permalink Reply by GoGoRainbow on September 4, 2009 at 4:36pm

coool

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Permalink Reply by Julia on September 4, 2009 at 9:55pm

Wouldn't this suggest that new dwarf dogs would show up with some regularity? Of course, 19 times may be a high frequency. Or is the theory that this event happened once and the various breeds were descended from this dwarfish "Eve?" That doesn't seem plausible from what I think I know about dog breeds. The abstract was a tempting tidbit, but a little knowledge can make my head explode.

Julia

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Permalink Reply by John Wolff on September 5, 2009 at 12:43am

You are right: the mutation occurred only once, and this retrogene is descended from one canine "Eve" . All of the dwarfed breeds mentioned share this one tiny bit of one common ancestor. They call this a "founder effect".
Dwarfism occurs regularly but rarely in all mammals, but I 'spect that's the result of random and various damage to genes controlling the growth of the long bones. We are complicated mechanisms, and each part of us can malfunction, and given enough chances, each part will malfunction. I'll bet there's an hereditary disease for every gene in the genome: genes get damaged by cosmic rays, mutagens and other accidents, and if both copies of an important gene are damaged, that's a problem. Sometimes, if only 1 of them is damaged, that's a problem. This is what they call a "loss of function" event -- a gene is busted, so it can't do its job. So maybe you get an occasional dwarfed puppy, cat, or mouse from some other mutation, but those are quickly lost.
This FGF4 retrogene thing is a "gain of function" -- a new gene that got there by accident and is doing something it's not supposed to do, but it was selected for and preserved by human breeders.

The biology of this is fascinating. In the 1950's, after Watson, Crick, Franklin and others discovered that DNA i s the chemical of heredity, someone promulgated what they called the "Central Dogma": that genetic information flows from DNA to RNA to protein. The info is stored in DNA, it's translated into RNA, then transcribed into protein, the stuff that actually does the work. Note! Whenever anybody promulgates a dogma, you know it's wrong! It turns out that RNA, not DNA, was the original molecule of life. DNA evolved later, because it's a better information storage medium (DNA is ROM; RNA is RAM). So the information flow is more accurately: RNA -->DNA -->RNA --> protein.

The enzymes that make DNA from RNA not not exist in our normal biology, but they remain as molecular fossils in RNA viruses. They are called "reverse transcriptases". They copy the message from RNA into DNA. This is the reverse of the process you learn in high school biology. Every RNA virus codes for a reverse transcriptase enzyme that makes DNA from RNA (the opposite of what they taught you in high schol biology). These are called "retroviruses" (HIV is one). They are molecular fossils from the ancient, original RNA world, when RNA was the only molecule of life.

So what happened was this: a reverse transcriptase enzyme, likely of viral origin, copied the messenger RNA of this FGF4(fibroblast Growth Factor 4) back into DNA, and it got inserted into a sperm or egg cell's DNA. It's a bizarre gene, containing no "introns" (junk DNA that has to be spliced out); it's also called cDNA or 'copy DNA' ". They call these "retrogenes" [I'd never heard of them before.] Usually, they get inactivated by mutations, but in this case, it was selected and deliberately preserved by humans.
Apparently our genome (90% of our DNA is junk) is littered with such stuff, nonfunctional trash, but occasionally it can be useful, a source of genetic novelty.
Somebody sometime somewhere got a dwarfed puppy, though it was cool, and bred it, just for the heck of it. Later, somebody found it useful: short-legged dogs can go down badger holes, and are cheaper for poor framers to keep as herders. Voila: dachshunds, corgis, bassetts. All of our dwarfed dogs owe their short legs to that one puppy.

DM is similar: a single point mutation, shared among all the breeds. Boxers, GSDs, corgis, Chesapeake retrievers -- they all share this one tiny bit from one single common ancestor.

And you thought you had just a dog.

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Permalink Reply by Julia on September 8, 2009 at 6:54pm

How long ago would this "Eve" have appeared? How long would it take to a) stabilize the trait, and b) develop little Eve into 19 different breeds? Your suggestion that it was a poor farmer indicates it would be after we developed agriculture. 4000-5000 yrs? Herding dogs would have to be developed in an area that had domesticated large animals, maybe Asia. I have no idea when that happened.

I'm trying to imagine that original generic short-legged puppy, and it's a funny image. I'm visualizing a labradoodle with six-inch legs. Chasing water-buffalo. Maybe living in China. Remember, the Chinese bred those tiny little lap dogs. They liked small.

I'm guessing that retogene would stabilize quickly, but the breed differentiation?

Julia

BTW, when I studied genetics in college, I knew nothing about RAM and ROM. (Nor did anyone else.) I like your analogy.

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Permalink Reply by John Wolff on September 9, 2009 at 1:49am

I'd think the retrogene could've been active immediately , although I don't understand how it would've been inserted where a promoter would transcribe it, unless by pure luck, or maybe its original promoter got transcribed into mRNA by mistake and then retrotranscribed back into DNA.
If it's dominant, it would dwarf its first owner; if recessive, two copies would be necessary (this would be likely if sibs or cousins of the founder mated). Whatever, somebody got a dwarfed puppy and bred it for its novelty, I'll bet. Once human breeders decided they liked it, its survival was assured. Maybe the first dwarfed dogs were pets & lap dogs, as you suggest, and then later breeders developed useful working breeds like bassetts, corgis, dachshunds.
By "...poor farmers..." I meant the Welsh; they would not have originated this mutation, just taken advantage of it.
The retrogene has spread worldwide with its human partners, but a map showing the origins of these breeds would be interesting.
The founder of this mutation antedates the radiation of all of these breeds, by definition. Nobody knows how long that radiation took, but it might have been on the order of only thousands or even hundreds(?!?) of years. The domestication of the Russian silver fox took only 50 years or so (see below, don't miss that fascinating story!).

silver fox.pdf

domesticated silver fox

LOOK AT THIS FACE!

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Permalink Reply by Potus on September 5, 2009 at 12:29am

I think I remember this topic in my high school biology book.

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