Of Mice and Twins

Nearly identical twins and curing colorblindness in mice
Usually I write these "Genetics in the News" articles on some matched set of stories. Like when there are two stories that come out on lung cancer. Or evolution. But this week two cool stories came out that I wanted to write about. They are completely unrelated but really interesting. The first is about a new kind of twin. Usually twins are classified as fraternal or identical. This type is somewhere in between. And in the second, a human gene was put into mice that let them get beyond their red-green colorblindness. They can now see the same colors as us!
Fradentical Twins
Twins are fascinating. And not just to fathers of twins like me. No, there is something about them that piques people's interests. There are fraternal twins. These are the twins that can run in families. They start out as two eggs that are each fertilized by a different sperm and are no more alike genetically than any two siblings. There are various ways to mix and match these kinds of twins too. There are garden variety fraternal twins who share the same dad. Rarely, fraternal twins can be half-siblings when they have different dads. Sometimes fraternal twins can recombine back together to make something called a chimera. These folks have both twins' cells all mixed together in a single person. Some of their cells have one twin's DNA. And some cells have the other twin's DNA. And of course there are identical twins. These folks start out from the same fertilized egg. The embryo then splits at a very early stage into two bunches of cells. Each bunch grows into a new person. Now there is a new kind of twin. This twin happens when two sperm from dad fertilize the same egg. Usually a fertilized egg like this quickly dies because 3 of each chromosome are just too many. But apparently, sometimes, this fertilized egg with too much DNA can rescue itself. And form two people. In a recent case something like this happened. Both twins were chimeras. But they shared exactly the same DNA from mom but had different DNA from dad. Now how this happened is all theory at this point. One idea is that the egg started out with double the number of chromosomes. This happens in some other animals and is called parthenogenesis. The two sperm fertilized this egg and this zygote with four sets of chromosomes split into two cells with the right number of chromosomes. These cells then divided and the big bunch of cells split into two bunches. That grew into two people. Another possibility is that two sperm fertilized a normal egg. Then, somehow, the DNA from mom duplicated itself. Then the same process happened that led to the two chimeras. It is amazing all of the different combinations you can get with just sperm and eggs. Fraternal, identical, and now something in between. And add to this chimeras. As DNA testing becomes cheaper and more routine, it'll be interesting to see how common these sorts of things are. The only reason the scientists found these new twins originally was that one twin was a true hermaphrodite. That piqued their interest and so they looked at 6000 different DNA markers to show that the twins shared the same maternal DNA. If this level of testing were done on everyone, who knows how common chimeras or fradentical twins might be.

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There are lots of
ways to make a twin.
The color red
And now for something completely different… Like many mammals, mice are red-green colorblind. Most people aren't colorblind because they have an extra gene, a long wave cone photopigment gene. Most mammals lack this gene. The long wave cone photopigment gene lets us tell the difference between green and red. Some scientists put this gene into a mouse and tried to figure out if it could see color. Now they didn't just do this for fun. They were trying to mimic what happened when our ancestors developed color vision (see below). So they could study the process. The scientists found that the mouse with the extra gene could tell the difference between green and red. As you can imagine, this isn't an easy thing to figure out. You can't just see if they drive through a red light. And you can't just ask them. The researchers came up with a very clever way to test the genetically engineered mouse. The test is a similar to one that was used to figure out the colors that dogs can see. There are three lighted panels. When a mouse touches the correct panel, it gets a drop of soy milk. Imagine that one panel is green and the other two are red. If the mouse touches the green panel, it gets its reward. A color blind mouse couldn't tell the difference between the green and red lights. But a mouse cured of its colorblindness could. The mice that didn't have the extra version of the gene picked the right light about one third of the time. Just what you'd expect if the little guys were guessing. But the mice that had both versions were able to get it right about 80% of the time. And this was with thousands of tests. So this mouse was no longer color blind. Cool huh? It is even more than cool because it shows that the mouse brain was definitely able to handle this extra information. Most likely our ancestor's was too. This experiment is a great first step in showing how our superior color vision may have developed. Details about color vision evolution As I said, we have a gene that lets us tell the difference between green and red. This kind of color vision is common in primates like us. But it evolved differently in New World and Old World primates. In Old World primates (like us), a certain photopigment gene was duplicated in our distant past. The duplicated gene then mutated over time to give the new long wave cone photopigment gene. This is a pretty common way that new genes evolve. Color vision came about differently in New World monkeys. What happened there was that they developed a version of their cone photopigment gene that could see long wave light. This is more like our blood type genes. We have one ABO gene that comes in three versions: A, B, and O. Since we have two copies of this gene (one from mom and one from dad), we can have the following possible combinations: AO, AA, AB, BO, BB, and OO. (Click here to learn why this only translates to 4 different blood types.) Color vision works similarly in New World monkeys. These monkeys have two versions of the same gene—one that sees medium wave light (M) and one that sees long wave light (L). Because of this, the only New World monkeys that are not color blind are the ones that have one of each version of the gene, ML monkeys. Some New World monkeys have two copies of the medium wavelength gene (MM). And some have two copies of the long wave length one (LL). These monkeys are colorblind. But some monkeys will have one copy of each (ML). These monkeys can tell the difference between an emerald and a ruby! One other complication. This gene is on the X chromosome. As you may remember, males have an X and a Y chromosome while females have two X chromosomes. What this means is that New World male monkeys are always color blind. They can have one version of the gene but not both. Females can have both versions at once because they have two X chromosomes. So some female New World monkeys are not colorblind. (Click here to get more details about X-linked traits.) The reason I went into this (beyond it being fascinating) is that the researchers set the mice up in the New World style. So at a spot on the X chromosome of these genetically engineered mice, there was either a gene for seeing long wave light or one for seeing medium wave light. What this means is that some female mice had good color vision. But none of the males did.
Scientists added a human
gene to mice to cure their
color blindness.