The science of calico cats

Why is it that when you cross a black cat and a ginger cat, you get some black male kittens, some ginger male kittens, and female kittens with a calico pattern?

It has to do with X chromosome inactivation, something all female mammals (including you, ladies) go through as embryos. A male cat embryo has a fat X chromosome bursting with relevant genes and a puny, shrunken Y chromosome that gives him nothing but balls, to be blunt about it. Meanwhile, a female has two of those fat X chromosomes. She can’t express the genes on both in the same cell – it would create too many proteins and gum up the system.

Her DNA has an ingenious way of protecting itself from such disasters. Early in gestation, one X chromosome in each cell gets “deactivated” – bound up in proteins and effectively closed for business – through a fascinating process I’ve been learning about in an online class called Epigenetic Control of Gene Expression. The details are not for those uninitiated in molecular biology, but the gist is that female cats have different cell lines in their bodies. In some lines, the paternal X chromosome (the one from dad’s sperm) will be active. In other lines, the maternal X chromosome (the one from mom’s egg) will be active. Since the genes for coat color are on the X chromosome, female kittens will express mom’s genes in some areas and dad’s genes in others. That’s what gives calico cats their trademark patchwork look.

It’s also why you rarely see calico toms. Male cats don’t need X inactivation because they only have one X chromosome to begin with. As cat breeders know, there are exceptions – sterile male calicos with an XXY karyotype, the feline equivalent of Klinefelter syndrome.

The study of calico cats was important for the development of epigenetics, or the study of how genes get turned on and off inside cells. In 1949, Murray Barr was examining cells taken from calico cats when he noticed tangled blobs at the edge of the nuclei. These “Barr bodies” were inactivated X chromosomes, and Mary Lyon would describe them in a 1961 paper that foreshadowed decades of epigenetic discoveries to come. So if you own a calico cat, you own a piece of scientific history…kind of.

In humans, X chromosome inactivation has profound implications for diseases where the pivotal gene is on the X chromosome (like hemophilia) and diseases which result from a person having too many chromosomes (like Down syndrome.) Down syndrome is an interesting case because researchers just figured out how to silence the extra chromosome that causes it using a process that mimics X inactivation – in a test tube, at least. Let’s hear it for the scientists!

Meow!

Related articles

• Research Shows Inactivation of Extra Chromosome Responsible for Down Syndrome (SGMO) (streetinsider.com)
• The Demoiselle of X Inactivation: 50 Years Old and As Trendy and Mesmerising as Ever (PLOS genetics)

Where do sunburns come from?

Last Monday, I reached over the stove while I was cooking and bumped my wrist against a hot saucepan, sustaining a semicircular blister burn. That Saturday, when my thermal burn was nearly healed, I went to Knoxville Pridefest in a sleeveless blouse and got a sunburn on my shoulders. As I write this, my week-old sunburn is shedding little pieces of skin onto the inside of my T-shirt.

These annoying but altogether normal experiences had me wondering: why do sunburns and thermal burns look and feel so different? Why did my thermal burn heal without peeling everywhere? Why do thermal burns hurt immediately, while sunburns glow warmly but painlessly for hours before you really feel them? And why does one increase the risk of skin cancer while the other does not?

As it happens, science has the answer! Well, science still has to work out the minute details, but on the basic level it has the answer.

When sunburn occurs, ultraviolet radiation penetrates the nuclei of the skin cells and mutates the DNA within. The mutant DNA gets transcribed into mutant bits of non-coding microRNA, which disseminates and triggers an inflammatory response. This inflammation is what makes the sunburn red and warm. If the mutations are pronounced enough, the cells in the first layer of skin will die and eventually peel off. The body has processes that stop the crazy sunburn mutations from spreading, but every time you get a sunburn it increases the statistical possibility that mutations will stick around – and that’s why sunburns increase the risk of skin cancer.

So sunburns are caused by DNA mutations from radiation. Real life is so much less glamorous than superhero comics.

A thermal burn from a hot stove, by contrast, happens when excessive heat melts the proteins inside the skin, causing it to break down. You feel this immediately, which is a good thing when you think about what would happen if you just left your hand sitting on a hot saucepan. Thermal burns have nothing to do with skin cancer because they do not mutate DNA.

It just goes to show that even common experiences can be an opportunity to learn some fascinating science – or, if you’re really smart, to come up with some fascinating science.

The best MOOC ever just ended

This week marks the end of a massive open online course called Introduction to Biology: The Secret of Life. This course, an adaption of human genome unwraveler Eric Lander’s Bio 101 class at MIT, was offered (and may be offered again) by all-star online education platform edX. And as it happened, it consumed my life for three whole months.

I am going to miss it so much.

The principle joy of taking this course was Dr. Lander’s feisty, creative teaching style. I’m sure that I missed out on some things experiencing it on video only, but the elitists who snub MOOCs on this basis forget that most of us are never going to know what it’s like to attend an MIT lecture in person – the effect of a charismatic hologram professor on the student is diluted, but still valuable. I admired Dr. Lander’s manner of structuring the material, which involved tying the textbook material to the historical progress of genetics, biochemistry, and molecular biology. The few MIT chemistry lectures I watched before accepting that I needed to take calculus first followed a similar multidisciplinary-historical approach, suggesting that this may be part of the MIT model of education in general. If so, MIT is awesome.

Platonic crush ahoy!

I loved how current some of the material was. At one point, Dr. Lander was discussing RNA-induced silencing complexes, and he said “This isn’t in your textbook, but it’s in your body.” That’s how fast the discipline of biology is moving, and that’s the value of having MOOCs in STEM fields. A rockstar prof involved with cutting-edge research is going to have access to the most recent advances and know how to teach about them. S/he will also have amazing stories to tell – this year, Dr. Lander wrote a brief to the Supreme Court regarding the pitfalls of gene patents, and it was cited at the hearing!

Please grant me one more paragraph of shameless gushing: some of the software available with the course was incredibly cool. It allowed students to solve problems involving actual protein structures and genome sequences. Now, there were a few bugs that drove us all crazy in the beginning, but all in all it was a good system – there is nothing like solving a biology problem with a real genome. There is nothing like knowing that one’s homework is real.

I came within five points of earning a full certificate in this course as opposed to an auditor’s certificate, but I didn’t make it. This is only, and I mean only, because I went through a disorganized period in May where I missed the second half of the midterm exam. I guess I learned some lessons about writing things down on my calendar. Depressing, certainly, but I cannot consider it an outright failure, as it is not going to be carved in stone on any transcript. The point of most MOOCs, as they currently exist, is what knowledge one can take away from them; 7.00x was stellar in this regard. I’m happy to take the auditor’s certificate as a souvenir/physical token.

Earlier this year I took a MOOC called Introduction to Genetics and Evolution, courtesy of Dr. Mohammad Noor of Duke University in partnership with Coursera. I did earn a full certificate in that one, as well as two hours of college credit and a distinction badge. When I was banging out Hardy-Weinberg equilibrium problems as part of Introduction to Genetics and Evolution, I remembered thinking, “Wow, I could do this every day for the rest of my life!” Normally statements like this are just hyperbole (“Mmmm, Miss Carrie, I could eat this cornbread every day for the rest of my life!”), but when they concern things like biology, computer programming, sewing, writing, or fixing cars, that’s an inner voice to which one should pay heed. It reminds me of being that little girl who would only listen to fairy tales if her mother replaced all the characters with anthropomorphic viruses and bacteria. Seems I’m still that little girl.

To close with a quote from Dr. Lander’s lecture on gene patents:

There are choices we have to make as a society, and different societies make different choices. It’s done in different ways in different places, and they may value things in different ways. But it’s important that as much as we may focus on alpha helices and proteins and telomerase and things like that, we recognize that what we’re doing does spill out and affect the rest of society, and as scientists, or people just learning about science, it’s important to think about bringing that knowledge to these social questions…That’s what we want people to be able to do, to be able to take knowledge from science and then go apply it to different social situations, combining with real human values. In the end, the values make a big difference to where you’re going to come out. But if you’re not informed by good science, values alone aren’t going to be enough to get you to a good answer.

Indeed, indeed.