QUEST Community Science Blog

Human and chimpanzee chromosomes are very similar.
Note that human chromosome 2 is very similar to a
fusion of two chimpanzee chromosomes.

For the last few weeks I have been corresponding with someone about intelligent design (ID). More specifically, we have been chatting about why humans have 46 chromosomes and most of the great apes have 48.

To me, this is great evidence for evolution. Why? Because if you look at the chromosomes closely, you can see that human chromosome 2 is really just a fusion of two great ape chromosomes.

The idea is that a few million years ago, a common human-chimpanzee ancestor of ours had two of his or her chromosomes fused together. This sort of thing happens all the time even today. Around 1 in 1000 live births has one of these kinds of fusions.

Then, probably through chance,this ancestor with the fused chromosomes went on to found the human race. Now people have 46 chromosomes and chimpanzees have 48.

An alternative explanation is that the designers fused the two chromosomes together when they created humans. The idea would be that the designer wouldn’t create every plant, animal, bacteria, and virus from scratch–why reinvent the wheel every time? Instead the designers would mix and match parts that worked.

So as part of the process of designing a human, the designer fused two ape chromosomes together. This would presumably be simpler than creating a human chromosome 2 the way the other chromosomes were made.

The difficulty with this idea is that there is no obvious advantage to having 46 chromosomes instead of 48. What matters is our DNA, not how it happens to be packaged.

It is possible that there was some advantage to fusing the chromosomes together. For example, maybe a new gene was created at the fusion point. Or maybe genes that were shut off before were now turned on in the new fused chromosomes.

There isn’t any evidence of these kinds of things. And even if there were, a designer who can easily put in the 60 million or so differences between humans and chimpanzees should be able to accomplish whatever results a chromosome fusion gives more elegantly than sticking two ape chromosomes together.

Also, when you look at the fusion point, you can see that the DNA isn’t exactly what you would expect if a fusion happened in the last 10,000 or even 100,000 years. The results look more like an event that happened millions of years ago.

The ends of a chromosome have a defined sequence of DNA repeats called a telomere. The DNA at the fusion point looks very similar to a string of telomeres (as we would expect from a fusion) but it isn’t perfect. This is just what you would expect if the fusion happened millions of years ago. Because our DNA gets changed a little all of the time.

The environment or even our own cells can cause the wrong letter to end up in our DNA. Our cells are pretty good at fixing these mistakes but they don’t catch them all. What this means is that our DNA builds up mutations over time.

When an unfixed change happens in a sperm or egg, then it is passed down to the next generation. If the changes that aren’t fixed happen somewhere important, then they are selected for or against. But if they’re neutral, then they just build up over time. Scientists can even use these sorts of errors to predict how long ago something happened. Or to trace human migration patterns.

These DNA changes at the fusion point do not fit with ID if they don’t serve a purpose. Otherwise, why put them there? It will be interesting to see the results of experiments that might show if these sequences matter or not.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

These fish can tell us a lot about ourselves.

Species often end up a different color when their environment changes. And humans are no exception.

When people moved out of Africa tens of thousands of years ago, they were dark-skinned. Now when we look around Northern Europe or parts of Asia, we see much lighter people. What happened?

A common explanation has to do with sunlight and vitamin D. When people moved north, they got less sun. Less sun means less vitamin D and awful diseases like rickets.

Anyone who moved north and had lighter skin ended up getting more vitamin D and did better than their darker neighbors. After awhile, most of the population had light skin.

This is all well and good, but what happened at the gene level to cause this transformation? One way scientists are learning about how humans ended up with lighter skin is by studying fish. For example, the zebrafish has taught us a lot about why Europeans are often so pale.

The zebrafish is an important model system that scientists use to study vertebrate development, human disease, and lots of other things. A common mutant fish that scientists use in these studies is called “golden.” These fish have lighter, yellowish stripes instead of black ones.

Scientists discovered that these mutant fish had yellow stripes because of a single DNA difference (or SNP*) in their SLC24A5 gene. When fish have this DNA difference, they have yellow stripes.

These scientists next looked for this gene in people. What they found was that most of the people they looked at had two copies of the “black stripe” version of the gene. Except for Europeans. They tended to share a common SNP in their SLC24A5 gene that the scientists went on to show is a big part of why many Europeans have lighter skin.

Another group of researchers decided to dig a bit deeper and find out when this transformation happened. By looking at the DNA around SLC24A5, they found that lighter skin came to dominate Europe around 6,000-12,000 years ago. At first this result is a bit confusing because humans moved into Europe around 40,000 years ago. Why did it take so long for lighter skin to become the norm?

Scientists can’t know for sure but one idea is diet. Around this time, Europeans started to grow their own food. And a farmer’s diet has less vitamin D than does a hunter-gatherer’s diet. Maybe the lack of sun only started to affect Europeans after they started growing their own food. Then, after a relatively brief time, most Europeans ended up fair-skinned to get enough vitamin D.

This gene doesn’t explain all of skin color. For example, it doesn’t explain the difference in color between Northern and Southern Europeans. Or why some Asians have fair skin. But it does explain a good deal of European coloration. Thanks, zebrafish!

*SNP=single nucleotide polymorphism

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

DNA magnified 850,000 times through a scanning electron
microscope
DNA day is coming up on Friday April 25th. This annual celebration of genetics and genomics was set up in 2003 to commemorate the sequencing of the human genome and the 50th anniversary of the solving of the structure of DNA.DNA day was thought of as an opportunity for teachers, students, and the general public to learn about DNA. And to have fun with it.

This should be a chance to pull DNA out of beef, strawberries, kumquats or even yourself and learn that you have around 100 billion miles* of DNA inside of you. In case you’re interested, that’ll reach from the Earth to Pluto and back when Pluto is farthest from Earth. And that is one person’s DNA.

Add up everyone’s DNA in the world and you get 125 million light years of DNA. (At least I think you do… these numbers are getting ridiculous!) That’ll get us to the galaxy Andromeda and back 25 times. Add up all the DNA on Earth and… OK, that’s probably enough of that.

There isn’t just a lot of the stuff but it is amazing to me how similar all human DNA is. The latest estimates are that people are around 99.5% the same at the DNA level. That means that all those light years of DNA are mostly the same old thing just copied over and over.

Notice the mostly. With 6 billion letters of code in every person, a 0.5% difference means 30 million differences between you and me. It is these differences that make me look different than you. And to a varying degree, make me act differently than you.

This code doesn’t work in a vacuum either. The environment can change how it works which is a big reason identical twins aren’t really identical. And one of the reasons why it is so hard to figure out the genetics of complicated diseases like diabetes or heart disease.

Our DNA also changes with time. Things in the environment might damage it. Or our own cells can make mistakes when they make copies of themselves. What this means is that today’s light years of human DNA will be different than the same stretched out DNA in 100 years.

This also means that you have some cells in your body have different DNA than the rest of your cells. And if a DNA change happens in sperm or egg cells, then they are passed on to the next generation. Which is where all the wonderful diversity around us originally came from.

As you can see, there is a lot about DNA to celebrate. It is huge and mysterious and we’re just starting to get a good grasp on what it is all about.

I plan to spend the morning of DNA day at The Tech Museum in San Jose exciting kids (and hopefully some adults) about DNA by running five different hands on genetics programs all at once. It’ll be a blast!

I have searched high and low for a list of DNA day activities here in the bay area but I haven’t come across any. Does anyone know about other DNA day celebrations here in the bay area?

* Each cell has 6 feet of DNA and we are made up of around 50-100 trillion cells.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

There is a lot we don’t know about our DNA and how it works. While there seems to be news every week about genetics, scientists are still in the early stages of finding out what effect our genes have on us (check out this post from another QUEST blogger, Dr. Barry Starr). That’s what the researchers at the Canine Behavioral Genetics Project are doing. But in this case, they’re looking at dog DNA.

It turns out that human intervention in the form of hundreds of years of dog breeding has created a unique genetic experiment. Because purebred dogs are in essence closed gene pools, it’s much easier for scientists to compare of DNA of dogs within a breed. The Canine Behavioral Genetics Project is doing this to find the genes that are associated with behavioral disorders, like anxiety and fear. They also hope to use that information to find the genes in humans that are associated with similar disorders.

Millions of problematic dogs are given up each year in the U.S. And while the UCSF team definitely believes that training is a huge part of dealing with dog behavioral disorders, they’re also hoping to understand the genetic influences. Many owners are starting to use medications to help treat these problems, like doggie Prozac. But Melanie Chang, a member of the UCSF team, made a good point to me. Owners tend to think their dog’s problems are the owner’s fault. Sometimes there are other forces at work.

Listen to “Doggie DNA: Human Genetics through Dogs” online, as well as find additional links and resources. Also, check out the photo set with behind-the-scenes photos.

Lauren Sommer is an Associate Media Producer for QUEST.

By 2050, as our population ages, 15 million Americans will suffer from Alzheimer’s disease – triple today’s number. There is no cure for Alzheimer’s, but several treatments can help alleviate its symptoms, and many research projects aim to understand the disease better and find a way to fight it. In this QUEST story, we visited researchers at San Francisco’s Gladstone Institutes, who are looking for a gene that may hold the key to a cure.

There are many others also working in the field. The Alzheimer’s Association has information about current treatments available. The National Institute on Aging gives a good overview of what avenues of research are being pursued to better diagnose the disease and find a cure. A team of health professionals at the UC Davis Alzheimer’s Disease Center can provide a diagnostic work-up, as well as enroll patients in several ongoing clinical trials.

Watch the “Alzheimer’s: Is the Cure in the Genes?” TV Story online, as well as find additional links and resources.

Gabriela Quirós is a Segment Producer for KQED-TV, and is the producer for this story.

Red hair genes will be diluted but will not go away.I got a call last week from a reporter in Virginia. Someone had come up to her in a bookstore to offer her condolences about her kind dying out. She is a redhead.

The guy from the bookstore must have read one of the stories about the imminent demise of redheads that flashes across the media landscape every few months. People with red hair have to deal with headlines like:

“Redheads Set for Extinction.”
‘Will rare redheads be extinct by 2100?’
“Gingers Extinct in 100 Years.”

The reporter suspected these stories weren’t right and wanted to write a story about it. She called me to get some science to back her up. I was able to reassure her that redheads weren’t going the way of the dodo. They’ll become much less common, but there will probably always be red haired people around.

To understand why redheads will fade but not disappear, we need to dig a bit deeper into how red hair works. Red hair happens when both copies of the MC1R gene do not work properly. (Remember we have two copies of almost all of our genes–one from mom and one from dad.)

So if you’re a redhead, you inherited a nonworking copy of MC1R from both your mom and your dad. If you get a non-working copy from only one of them, then you won’t have red hair. You’ll be a carrier.

Right now redheads are at an artificially high level in the human population because their recessive red hair genes are concentrated in North America, Europe, and Australia. For example, 10% of Ireland and 2-6% of the U.S. has red hair.

These numbers are maintained because carriers and redheads keep making new redheads with each other. But as barriers go down, their red hair genes will flow out of these populations and into the human gene pool.

Red hair genes will become diluted in this pool but they won’t be completely swamped out. Even as redheads decline in numbers, their genes will remain constant. It will just be less likely that two carriers and/or redheads will meet and have babies with red hair.

This is all interesting but it got me to wondering about how many redheads there will be in the distant future when all the mixing is said and done. We can use something called the Hardy Weinberg equation to figure this out.

This equation works great for simple dominant/recessive traits like red hair if we know how many of each gene version there is. To do this, we need to figure out how many redheads and how many carriers there are in the world.

It is easy to figure out how many redheads there are–you can tell who they are just by looking at them. But figuring out carriers is a lot harder. We can make guesses based on the number of redheads (again using Hardy Weinberg) but until we sequence a lot more MC1R genes, they’ll only be guesses.

The numbers I have seen floating around are that around 1% of the world’s population has red hair and that around 4% carry the red hair version of MC1R. This means that there are around 65 million or so redheads in the world and 260 million carriers. (This sounds high to me but these are the numbers out there.)

When we use these numbers and apply the Hardy Weinberg equation, we end up with a final percentage of redheads of 0.1% or 6.5 million. This is quite a fall from current levels but they are hardly wiped out!

There are lots of assumptions* in these calculations that might cause the number of redheads to actually be more or less than 0.1%. But unless there is some red hair specific catastrophe or people start burning them as witches again, redheads are here to stay.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

*Some assumptions used:

1) There are no barriers to finding partners
2) The 4% carrier number is an accurate one
3) Two non-workingMC1R genes produce red hair in all genetic backgrounds
4) Other assumptions described here

Genetically, we’re all pretty much the same. A massive volcanic eruption 75,000 years ago may be why.

Lake Toba is all that is left of the volcano
that nearly wiped out mankind.Last blog I talked about how East Africans are genetically more diverse than Asians. Who are genetically more diverse than Native Americans.

From all of this you might have concluded that people are pretty different from each other. They aren’t.

People are surprisingly similar at a genetic level. For example, any two people from anywhere on Earth are more similar than two chimps from the same troop. Why are we all so alike?

One possible explanation is that something in our collective past nearly wiped us all out. And we all come from the few survivors who were left.

A likely candidate for this near annihilation event is the Toba volcanic eruption that happened in Indonesia 75,000 or so years ago. This eruption was huge.

It was equivalent to around 1 billion tons of dynamite and was about 3000 times more powerful than the Mount Saint Helens eruption in 1980. It also may have reduced the average global temperature by 5 degrees Celsius, darkened the world for 5 or 6 years, and plunged the world into a new Ice Age.

As you might imagine, this eruption had dramatic effects on species around the world including our own. Estimates of how many people were left range from around 1000-10,000 breeding pairs. The theory is that we are all so alike because we share these survivors’ DNA.

Whether true or not, a bottleneck in our past would not make us unique. Lots of species go through these near death experiences.

Scientists think cheetahs went through one around 10,000 years ago. Cheetahs are all so similar genetically that veterinarians can do skin grafts with “unrelated” cheetahs.

And of course, people have created bottlenecks in species too. For example, in the late 1890’s there may have only been 20-100 elephant seals left in the world because of hunting. Now there are at least 150,000 spread across the west coast.

Species are in danger long after they go through a bottleneck. They have a pretty limited gene pool which means they may not be particularly healthy and are in danger of being wiped out by, for example, a single disease. Humans are probably OK in this regard (consider natural resistance to HIV for example) but elephant seals, bison, and cheetahs, and many other species may not be.

Fortunately for us we successfully came through our bottleneck. Hopefully, the animals that we’ve nearly wiped out will too.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

Last blog I talked about how scientists turned skin cells into embryonic stem (ES) cells. This was big news because scientists can now make an ES-like cell without destroying an embryo.

This blog I thought I’d talk about how scientists have used these cells to cure a mouse’s sickle cell anemia. If the mouse stays cured, this is a hugely important finding.

First some terminology so I don’t have to keep saying, “skin cell turned ES cell.” Scientists are now starting to call these cells iPS for induced pluripotent stem cells and I figured I’d jump on the bandwagon too. (Pluripotent is just a way to say that a cell can turn into lots of other kinds of cells).

Now as you probably know, sickle cell anemia is a genetic disease that is more common in people whose ancestors came from areas where there was lots of malaria. In sickle cell anemia, the red blood cells “sickle up,” forming crescent shapes. These shapes can’t fit in the smallest blood vessels causing the problems associated with the disease. Right now there are treatments but no cure.

The way to cure the disease is to fix the broken hemoglobin gene in the cells that make red blood cells. Since red blood cells are all replaced within a few months, this would lead to a cure pretty quickly.

Unfortunately, fixing a gene is not like falling off a log–it is really hard to do. The scientists in this study decided to try it with iPS cells. Basically they replaced the mouse’s blood stem cells with newly repaired ones so that the new blood stem cells made healthy new red blood cells. The mouse has not shown signs of sickle cell anemia for 12 weeks so far.

I don’t want you to come away thinking that it was an easy thing to do. It wasn’t (see below). But it does show that it is possible to treat and possibly cure sickle cell anemia in mice using iPS cells.

To move it to humans, we need to make sure that the treatment sticks. When these kinds of things have been tried with gene therapy, the cure almost always wears off over time. It shouldn’t happen at the DNA level with the way they did their experiment, but we need to wait and see.

The scientists also need to find genes that can turn a skin cell into an iPS with less risk of causing cancer. And to find better ways to get these genes into the skin cell so that, again, the treatment doesn’t cause cancer.

Even taking all of this into account, this is a very promising first step. Curing a genetic disease with stem cells that do not get rejected by the recipient’s body is one of the big goals of stem cell research. And these researchers may have accomplished this in mice.

More details on how to cure a mouse’s sickle cell anemia:

1. Add four genes to turn the skin cell into an iPS cell.

See the previous blogto see how to do this. To decrease the risk of the mouse developing cancer from these cells, the researchers chopped out one of the genes they used, the myc gene.

2. Use the ES cell to fix the gene using a process called homologous recombination.

Homologous recombination is a way to swap out one DNA for another. It is incredibly inefficient and we can really only get it to work at all in ES cells. Out of 72 cells, they managed to get one where one copy of the gene was repaired.* This result showed that homologous recombination would work in iPS cells which was an open question.

3. Turn the ES cell into a blood-like stem cell by adding the HoxB4 gene.

4.Destroy the mouse’s bone marrow and replace the cells with the new blood stem cells.

This is really just a bone marrow transplant using the newly created cells as the blood stem cells.

*In the end they had a mouse with one of its copies of the hemoglobin gene repaired in its blood cells. (All the rest of the cells including its sperm cells still carried the disease version of the hemoglobin gene.) The mouse exhibited no sickle cell anemia symptoms similar to most human carriers of the disease who have a single broken copy.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

latitude 37.3316, longitude -121.89

I love my cell phone. We have a serious relationship. One that may be biologically predetermined.

Let me explain. On New Year’s Eve I brought my phone with me to San Francisco’s Ocean Beach, where I traditionally go, rain or shine, to watch the year’s last sunset. I was by myself, but I wasn’t alone.

Oh no. I took snapshots of shimmering colors on the waves and sent them to faraway, landlocked friends who miss the sea. Another friend called to say she was also watching the sunset from her rooftop. Text messages flowed in.

I was connected.

Well, duh,” you could say.

And this “duh” is exactly what seemed kind of profound: we take communication for granted. Of course we can talk to each other and share things with each other. And of course we create new devices to make talking and sharing easier. Of course.

But why do we do this, seemingly to no end? And why is it that communication is such a vital and defining aspect of our experience as humans? Why, really, do I love my cell phone so much?

I think it’s genetic.

It’s probably not news to most of you that we humans appear to be wired to talk to each other. We’ve got that FOXP2 gene that keeps making the news, contributing to our linguistic capacity. In fact, many researchers believe that language was central to our success as a species and allowed a small group of humans to expand across the globe about 50,000 years ago.

Our genetic design for interaction seems to go beyond talking amongst ourselves. A University of Michigan study slated to be published next month found that social interaction has a positive affect on memory and on cognitive functioning. The people who had the most conversations with others seemed to be the sharpest, and this was particularly true among young people. This may mean that more socially-oriented humans had a bit of an advantage over those who tended to keep more to themselves.

We may be such social animals that we’re even hard-wired to simply need company. After all, isolation is one of the most universal methods of punishment. Another set of researchers at the University of Illinois at Chicago found that mice isolated from their comrades have lower levels of hormones that control anxiety, depression, and aggression. They believe that these responses are similar in humans. In other words, it’s possible that our brains keep us happier and functioning better when they’re interacting with other brains.

It makes sense that our predecessors who figured out how to play well with others and share their thoughts were the ones who got the best shot at passing on their genes. And it’s no wonder our species devotes such enormous reserves to inventions that make communication easier. The most basic systems of rock painting and alphabets have allowed groups to share stories or warn others of impending trouble. And creations that help disseminate these symbols–papyrus, the printing press, even the simple pen and paper–have had a major impact on how we exist with one another, as individuals and as societies.

These days, many of our communication technologies have gone beyond “watch for hungry bear” or “here’s my idea” into doing a kind of doubly-human duty. We not only use technology to convey thoughts, but also to extend our opportunities to create bonds with other people and to form social groups. Thus the popularity of the likes of Facebook, personals ads, and Flickr. In fact, if you leave a comment about this little ditty I’ve written, you’ve hopped on this double-duty train by becoming a part of Quest’s blogging community.

And so now, as my thumbs feverishly tap out text messages, I see my cell phone as more than a gadget. It’s the latest cousin of cave drawings and hieroglyphics. What it says about my own evolution I’m not quite certain. But no doubt my wireless admiration results from something buried in my chromosomes.

Robin Marks is a journalist and science writer who current serves as a Multimedia Projects Developer for the Exploratorium in San Francisco, CA.

latitude: 37.7595, longitude: -122.51

Scientists can now turn skin cells into embryonic
stem cells like these.(Image: Nissim Benvenisty)It is amazing how fast stem cell research is accelerating. Six months ago, we had to destroy embryos to get at their precious embryonic stem (ES) cells. Or we had to at least steal them.

Now, as 2008 begins, we can turn skin cells into ES cells in mice and humans. This is huge and here’s why:

1) No embryos need to be destroyed
2) No one needs to be cloned
3) ES cells derived from skin cells won’t be rejected by the body

So how’d the researchers do it? As with any important new finding, this one started out as basic research. And like many other findings, this one also started out not in humans but in an animal model system.

A Japanese group had been studying how a mouse ES cell eventually gets turned into a skin cell. In the end, they identified around 20 genes that were turned on to reprogram a skin cell into an ES cell.

The 20 genes the Japanese group identified are really master control genes. They are responsible for affecting how lots of other genes work. So, all a scientist would have to do is turn on these 20 genes in a skin cell and you’d get back to an ES cell. Sounds simple, right?

Unfortunately, scientists aren’t very good at all at turning on a specific gene in a cell let alone 20. To get around this limitation, the scientists decided to add the genes to a skin cell using gene therapy.

Unfortunately, scientists can’t easily add 20 genes to a cell with gene therapy either. This meant they had to find the bare minimum that might work. After much research, the group settled on four genes that could turn a skin cell into an ES cell.

Remember, this was all in mice. Now this same group (and another from the U.S.) has accomplished the same thing with a human cell. Both groups have taken a human skin cell, added four genes, and changed it into an ES cell.

We aren’t going to be curing diseases with these cells quite yet though. When the Japanese group put the mouse cells back into a mouse, 20% of them developed cancer. This is probably due to one of the genes they used (myc), as well as the way they did their gene therapy (viral mediated).

The U.S. researchers who converted the human skin cell were able to do it without the myc gene. This tells us there are different sets of genes that can work in this process. Hopefully scientists can discover a set of genes and a way to get them into cells that won’t cause cancer.

All this work got me to thinking. I wonder if scientists would have worked this hard to make ES cells from skin cells without George Bush’s ban on ES cell research. They certainly would have got there eventually but would they have gotten there so quickly?

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.

latitude 37.3316, longitude -121.89