Tag Archives: Genetics/Epigenetics

Posts about genetics and epigenetics.

Epigenetics Made Easy, Part 2

Epigenetics Made Easy, Part 2

Let’s reiterate from the previous post, just in case you need a recap:

All cells are made from other cells; we start with a few that are the same, and as the number of cells increases, they begin to differentiate and become cells for specific body parts.

DNA is the blueprint for the final product (a sexually mature adult human being, for illustration purposes.) RNA is a segment of DNA that begins the process of cell differentiation, but the mechanism that actually creates the proteins that build cells is the epigenetic process, which depends upon histones interpreting the genetic instructions.

Once we are full grown, our bodies are almost always replacing cells rather than making new ones, and the new cells may not be exact duplicates of the cells that created them.

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histone modification

Yes, there is such a thing as histone modification. Yes, gene expression (in the form of cells that follow specific genetic instructions) can be changed during the epigenetic process. Yes, it’s possible for some of these changes to become heritable (passed on from parent to offspring.) But let me explain what’s reasonable and rational about these possibilities.

Histone Modification

You’ve heard of this, but usually in the form of “you can change your DNA by doing this thing or eating that thing” which is, essentially, not true. Histone modification takes place on a cellular level, and changes in different ways depending on what the chemicals that can modify histones are doing. I’ll save the technical terms and illustrations for another time. Baby steps.

What happens is that while a cell is preparing to replicate itself, a chemical can make the histones do something differently from the way they were instructed, and that makes the resulting copied cell different from the cell that created it. Right now, we have some very specific examples of changes that depend on specific chemical exposures (some from external environment, some from internal environment.) DNA is huge. We have a hundred trillion or so cells in our bodies. The genome is almost infinitely diverse. There are very few examples right now of direct cause and effect, and each one we discover in the future will be just as limited.

The number of possibilities alone makes it pure speculation to assume that a food given to a pregnant mouse that changes her babies’ fur color and body shape is going to do the same thing for a fully-grown adult, or even something similar!

Now the add another layer of complexity, these are the things that can happen when you modify the histones in a cell:

*a beneficial gene is suppressed
*a detrimental gene is suppressed
*a beneficial gene is activated
*a detrimental gene is activated

So if someone claims that a food or something “methylates” your genes (besides being wrong) it could easily be a bad thing!

Changing Gene Expression

I mentioned the prenatal modification above, and that’s because it’s an important thing to study. Why? Because in order for histone modification to have any observable and verifiable effect, it needs to happen early. Think about it. If you modify the histones of a four or eight celled creature, then a lot more cells are going to be made not according to plans. In an adult, modifying a single cell, or even a few cells, out of all the cells in our bodies, is going to have minimal impact. In order to change gene expression in an adult, exposure needs to be intense enough or prolonged enough to influence a large number of cells.

I like to use the example of skin, partly because it’s a cell type that’s replaced frequently, and partly because we can see a lot of the possible changes to it. It’s a good way to illustrate that an environmental factor can produce a change that does not alter gene expression, and how the level of exposure can make a difference in whether an epigenetic change is even possible.

If you go out into the sun, your skin changes color. It could get burned, it could get tanned. But when those darker skin cells make their replacements and die, the replacements are your original skin color. You have exposed yourself to an environmental factor that has an obvious effect on your body, but it doesn’t change your gene expression. Why? Because the exposure was not prolonged enough that the visible change was messing around with histones while the replacement cell was being created.

On the other hand, if you’re out in the sun all the time so that your skin is constantly in a damaged state, then those cells are more likely to be in that damaged state when they’re replicating themselves. This could still even be temporary, but it could change gene expression so that the replacement cells are cancerous, for example. (Cancer is epigenetic – but it could be caused by environment *or* part of the plan all along.) So you need to expose the same group of cells to the same environmental factor for long enough that most of the cells begin reproducing with the alteration in gene expression. . .and that is not guaranteed to be a good thing, so don’t buy into the hype.

Heritability of Epigenetic Changes

Yep, this has been studied, too, and it does sometimes happen. The most repeatable changes happen when the fathers’ bodies have changed. I credit that to the fact that sperm are constantly being made, and things like stress hormones or chemical exposures, or starvation, can change what genes go into what chromosomes in the sperm cells at that time. Give the dads some time to recover, you get a completely different result.

Keep in mind that the normal set of instructions is the default. If you look at plants or other animals who’ve been genetically altered, a lot of times you’ll find that their offspring regress to the original, dominant form. In both human and animal studies, most of the epigenetic changes that were brought about by environmental exposure get passed down to the next generation, maybe the generation after that, and in a few cases, the third generation. Then things go back to normal.

I probably missed a few things, but I hope this is clear. Ask me stuff, tell me stuff. Thanks!

Epigenetics Made Easy.

Epigenetics Made Easy.

Tightly wrapped histones

No, not really. That’s a misleading title, but my hope here is that I can explain this in terms that are simple enough for people who aren’t scientists to understand. I’m hoping that because I’m not a professional scientist but am really, really into this stuff, the language and illustrations I use serve as a bridge for the gap in understanding.

So let’s start with the cell, and let’s use humans as an example. Even though epigenetics happens in every living thing, even plants, I want you to be able to identify personally with this so the information takes hold a little better. What do we know about genetics and conception and fetal development? Well, we start off with an assortment of genes and 46 chromosomes. We got all of them from our parents and grandparents and so on down the line, but it’s a mix between Mom’s side and Dad’s side, because her eggs start off with a random selection of 23 chromosomes (see my previous post about what random means) and his sperm also start off with a random selection of matching chromosomes.

Sperm meets egg, and there you go, 46 chromosomes in a single cell, and a complete, unique strand of DNA that has all the information needed to build a human body.

If you’ve watched videos of human development, you’ve seen how that one cell splits into two, two into four, four into eight, and then things really start to happen. In the beginning, each of those cells is exactly the same. Each time they split, they’re making another cell that’s just like they are. Remember this, because I’m going to mention it again later. . . Here’s how it looks, in case you haven’t actually seen it, in a video on in-vitro fertilization:

After this point, the cells begin to differentiate. Instead of simply reproducing copies of themselves, they start to become more specialized. They still contain all the DNA, but some of the instructions will be used, and some will be silenced. This starts with the transcription from DNA to RNA. What we used to believe (or at least what I was taught in school days in ancient times) was that the RNA was the sole messenger, containing only the information needed to make cells. That’s only kind of sort of true, and doesn’t explain a lot of confusing things that happen to human bodies. You see, it is part of the picture in cell differentiation, which is, to put it in simple terms, the process that makes one cell be a bone cell and another be a heart cell and another be a brain cell and so on. The RNA puts this in process by taking the pieces of the DNA that are needed to make a specific call and creating the proteins that manufacture that cell. With these instructions, cells continue to divide, but they’re not just making carbon copies of themselves.

We see this in fetal development because parts of the body from the brain, the eyes, the internal organs, to the fingers and toes, go from being kind of blobby and alien-looking, to functional and human-like. The manufacturing of differentiated cells continues throughout fetal development, and the differentiation is pretty much complete by the time a baby is born.

But there’s a piece missing – we know that RNA has instructions for making the proteins that manufacture differentiated cells, but it doesn’t make those proteins all by itself. This is where epigenetics comes in. The actual work of taking the orders from the RNA and making the proteins is done by histones. The DNA has the construction diagrams, the RNA is barking orders, the histones are doing the work.

This is still happening inside a cell. The cells are still dividing. It’s just that this epigenetic process is making two different cells out of one cell instead of two identical cells. The new cells aren’t coming out of nowhere, they’re coming from existing cells that are multiplying.

As we get older, we tend to go back to more of a model of cell replication. A cell duplicates itself, then dies after the new cell has been made. The epigenetic process takes place then, as well. Sometimes the cells won’t necessarily die, because we’re growing and need more cells. That’s done epigenetically, too, because the blueprint from the DNA says what the final adult product is supposed to be like, not just the infant version. As we get really older, the cells are trying to replace themselves, but they don’t do quite as good a job, and that’s an epigenetic process as well, because the instructions are getting messed up *after* the RNA. The histones just aren’t doing such a great job after a while.

The point here is that epigenetics is part of the process of cell development that is already written out in the DNA. The way it works without interference is genetic and heritable, and every single one of the many trillions of cells in your body was created the same way. The DNA has the plans, the RNA is the subcontractor, the histones are giving the orders to the proteins based on the instructions from the higher-ups.

Keep this in mind when you hear things about the amazing effects of environment on epigenetics. Yes, this is the part where things can get screwed up, because, yes, histones can be modified. But I’m going to save that for later, because this is a lot to absorb. I hope this makes sense, and if anyone has questions or corrections, please comment – I want to hear from you.

Epigenetics – I do not think that word means what you think it does.

Epigenetics – I do not think that word means what you think it does.

And I kind of have a bone to pick with Scientists who are actually contributing to the problem. Epigenetics is an essential biological process that takes place at the molecular level. Each one of the hundred trillion or so cells in the human body was created via the epigenetic process. Nothing has to magically happen. All you need is cells, food for the cells (usually glucose, yum!) and DNA.

Unfortunately, the amazing and fascinating research into epigenetics has led to a description of epigenetics as “genes plus environment.” If you are a scientist, or even understand science, you recognize that this does not mean that some sort of environmental factor from outside the body is necessary for the epigenetic process to take place. But if you’re a layperson, that’s exactly what you might think when you hear that. In fact, for quite some time I’ve been debating with a couple of people who believe in this magical concept of epigenetics, and you scientists (whom I otherwise love dearly) are just not helping!

The agouti mouse study that showed a change in coat color (linked along with other references in this previous post) was really exciting, and the public glommed onto it because there was the evidence, right in front of their eyes. In no time at all, alt-med proponents and the general public were certain that this was the answer to everything that was wrong with us. It was a great boon for supplement manufacturers, diet book writers, food conspiracy theorists, and anyone who was looking for something to blame for what was wrong with them (or society, but usually themselves.) I mean, clearly if what a mother mouse ate changed the color of her babies’ fur, then what horrible things are all these toxins doing to our genes?!?!

The thought seems to be that epigenetics is a highly unstable process that actually depends upon the correct “environment” in order to occur, and that even an unpleasant event in childhood can somehow upset it and result in a dramatic condition that can be passed down to one’s offspring. Once a person has gotten this idea into his head, it is darn nigh impossible to get it out. Homeopathic amounts of a “toxin” can have traumatic results, even worse than actual poisoning from that substance, because epigenetics. Psychiatric and neurological conditions are inflicted upon perfectly healthy infants by insufficient parental attachment or attunement. Everything is caused by environmental disruption of the epigenetic process, and everything in the environment messes up epigenetics.

Look, the reality is that what epigenetics does is take the information that’s been put into the RNA from the DNA, turn on the genes that are needed and turns off the ones that aren’t, then sends proteins off with the instructions to make new cells. At conception, when there are only a few cells, there’s not a lot of differentiation, but as fetal development continues, these instructions become more specific. “Make fingers.” “Make retinas.” “Make heart valves.” Stuff like that. During growth, the instructions are more like “make more of these cells.” During adolescence, it’s “make these a little different.” As we age, it’s “make another one just like this,” and “eh, what was that, sonny?”

The environment comes in because it is the epigenetic process during which an environmental factor can possibly alter the process, turning a genetic instruction on that should have been off or vice versa. It’s quite likely that this is what triggers many cancers that are strongly associated with exposure to a particular substance. But the possibility that exposure can impact gene expression is not the same as the inevitability of exposure altering gene expression. And this, people, is a big problem. Scientists, please think about this when you talk about epigenetics. Non-scientists, I’m going to put an explanation of how this works in the simplest terms I can come up with in another post.

Your Inner Fish

Your Inner Fish

I loved this book, and now PBS is making a miniseries with Neil Shubin. I can’t wait.

A long time ago, right after I read it, I put up a series of posts on a forum detailing the wonderful things I had learned from it. After a while, the threads were hijacked by people who just didn’t get it – or didn’t want to get it – and they disappeared into obscurity. But I stand by what I wrote, and now that this book is back in public view, I want to share these thoughts again. This is a long read, over 4,000 words, and it’s taken from a forum thread, so there are parts that don’t flow entirely well, but I don’t want to edit or rewrite it because it captures the wonder and excitement I felt when I first read the book and I don’t want to change that.

So settle down with a nice cup of tea if you’re ready to go below the fold.

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Chemotherapy is Poison, That’s Why It Works.

Chemotherapy is Poison, That’s Why It Works.

Unfortunately, I’ve known a few people who have had cancer over the years. Heck, I’ve had it – still do, but it’s not an aggressive, worrisome one. I’ve seen cancers cured with surgery alone. I’ve seen cancers cured with radiation alone. I’ve seen cancers cured with chemotherapy alone. I’ve seen cancers cured with a combination of two, or all three. I’ve seen cancers that have gone into periods of remission because of these treatments, allowing people many good years. And, of course, I’ve seen cancers that simply couldn’t be cured by anything. But what I haven’t seen is doctors pushing inappropriate chemotherapy on patients because they’re sadistic monsters who want to poison people.

“Cancer” is not a single disease, but over a hundred different diseases that form from a similar mechanism. Normally, cells in our body die off, and those cells are replaced. The cell death is called apoptosis, and different cells in your body apoptose at different rates (forget what you heard about that “every seven years” thing. . .) Because of a large number of factors, occasionally those replacement cells will be faulty. Your genetics cause a misreading of your DNA, or a mixup in the instructions from the RNA, or an epigenetic flaw causes a cancer cell to be expressed or a cancer suppressor to be repressed. Exposure to a known carcinogen can trigger the production of cancer cells in a similar manner – sometimes on its own and sometimes because you have a genetic susceptibility to the carcinogen. Age is actually the biggest culprit, because cell reproduction can degenerate in accuracy over time. For the same reason all the other cells in our body change as we age, and not for the better, a cancerous cell can be created instead of an identical replacement cell when the aging process interferes.
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What Does Random Mean?

What Does Random Mean?

I’ve been reading a lot of articles about scientific journalism, and what Scientists and Journalists need to change in how they release new findings to combat public misunderstanding. There are some great ideas there, and a lot of people committed to making this happen. The problem, though, is that science has a lot of concepts and vocabulary that are either exclusive to science (and impossible for non-scientists to understand) or are used differently in a colloquial context. So I’m going to start small and pick one. RANDOM.

If you’re having a conversation with someone and the word “random” comes up, you’re likely to think “something completely unexpected,” or “something without precedent,” or “something that just makes no sense.” “Random” started off meaning one thing to scientists and mathematicians and another to everyone else, and now it’s becoming a catchword for many other things that are even further removed from the strictest definition of “random.” Pseudoscientists and peddlers of dubious ideas and products take advantage of this by using the new popular understanding of the word to misrepresent or even mock science that uses it, so I want to set you straight.

Let’s start off with a straightforward explanation. “Random,” in science or mathematics, refers to a set or subset of existing things that is separated, combined, or put in order without any plan or pattern.

Take a look at A Million Random Digits with 100,000 Normal Deviates. This book has been around for a long time, and it’s an important tool for checking probabilities and mathematical formulae to make sure that they work with numbers that have no patterns. It’s not a very exciting read, obviously, but what you will find if you look at it is pages and pages of numbers. In other words, you will not find symbols, color dots, letters, or little drawings of cats. The numbers are random because they cannot be placed in any kind of sequence – as a simple example, you wouldn’t be able to add three to the first digit, six to the next, nine to the next pair, etc.

If you were talking to your friend about this book of numbers that was, like, totally random, your friend might reasonably expect to find those symbols, color dots, letters, or little drawings of cats. But your friend would be wrong; that wouldn’t truly be random since none of those things exist in the set called “numbers.”

So let’s look at this from the point where I see most of the misinterpretation of “random”. . .genetics. I want you to imagine two bags of marbles. I’m not going to specify how many, because we’re not going to get started on the difference between chromosomes and genes or anything like that. We’re just going to be very general and say that each marble represents a piece of genetic information.

two-sacks

One sack is filled with marbles that represent Dad’s genetic information, the other is filled with marbles that represent Mom’s genetic information. Now let’s say that Dad’s marbles are almost all primary colors, but there are a couple of purples, a few greens, one black, and one white. Mom’s marbles are mostly secondary colors, but she does have a smattering of reds, blues, and yellows, and one black and one white. So you reach into the bags blindfolded and grab a handful of each, and this is what you come up with:

two-sets-of-marbles

That’s random (although it’s unlikely that you’re going to get the single black marble and single white marble from each bag. I just wanted to use them.) Do you see any peach pits, or rocks, or silver marbles? Of course not. They weren’t part of the set from which you were randomly selecting. They’re not going to appear out of nowhere – and if they do, it’s not scientifically random.

Now let’s say that we’re going to pair them up. The only rule is going to be that the marble from Dad’s set can’t be paired up with the same color from Mom’s set. In real life, this happens fast, and the number of pairs is significantly bigger, but this is a decent symbolic representation. So across the top are the marbles we got from Dad, and below that are the marbles we got from Mom.

marbles-paired

Randomly we ended up with a unique combination – but still, there is nothing there that wasn’t present in the original set. Randomly we ended up with an extra blue marble from Mom. It could have been an extra orange, purple, green, red, yellow, black, or white marble – but it could never be a peach pit, or a rock, or a silver marble.

You could take all these marbles and put them in different sequences, but nothing is going to change the number of marbles, the colors, or which marbles came from which bag. You might get different pairs of colors, or all the same pairs but in different order.

Randomness, in science or mathematics, means that we have certain things that are givens. A set of numbers will contain nothing but numbers. A set of genes will contain nothing that isn’t already in the genome. Any random thing we look at will be comprised of something very specific that already exists. What makes it random is how it ends up being put together.

I hope that makes sense. Feel free to ask questions or add to the discussion.

Wednesday Links

Wednesday Links

A new study was published in the Journal of the American Medical Association about neuroimaging to determine response to medication or therapy in Major Depressive Disorder. It seems much more exciting if you don’t actually read it. Fortunately, Neurocritic did, so you have someone to explain what’s hope and what’s hype.

Paul Offit explains why we shouldn’t take multivitamins.

He also has a book coming out soon called “Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine” and USA Today covers some of the issues that make this stuff such a dangerous alternative.

And Darshak Sanghavi at Slate wonders why so many of us think we need to avoid gluten

Now, if you happen to be near Washington, DC, and you want to see some cool genetics stuff, hit the Smithsonian Museum of Natural History for an exhibit called Genome: Unlocking Life’s Code.

Teaching otters to use vending machines might not be the best idea, but it sure is cute to watch.

Wednesday Links

Wednesday Links

Yes, it’s been a while since the last set of links. I’ll try to do better. Enjoy these for now.

Carl Zimmer wrote an article on Fibrodysplasia Ossificans Progressiva for the Atlantic. One of the reasons I think it’s important to read stories like these is to see examples of the success that comes from investigating genetic origins of diseases. Another is to show that there are real reasons that a treatment may or may not be produced outside of the simple profitability of the treatment itself. All in all, this is a great story with some human interest thrown in for good measure.

I’ve often had the discussion with people about how even though we have names for colors, not everyone perceives them the same way. Well. . .who’d have known it? Apparently some of our perception differences arise from how we name the colors in the first place! Empirical Zeal discusses it in two parts. Part 1. Part 2.

Beyond Recognition: The Incredible Story of a Face Transplant
Yes, it’s graphic, but it’s also absolutely amazing.

Scicurious has an interesting piece about genes and environment. . .interesting not only because it shows an actual mechanistic result in the brain that can differentiate genetically identical mice, but also because those of us on SSRIs can take comfort in knowing our meds are assisting us in hippocampal neurogenesis.

Another thing that seems to be related to a mechanical malfunction in the brain is Body Integrity Identity Disorder, in which a person is uncomfortable with the very presence of a part of his or her body. Mindscapes: The man who needs to paralyse himself in New Scientist talks about some of the possible roots of this condition that makes people seek elective amputation procedures.

From Nature, an explanation of what a chemical is, and why it’s not inherently dangerous or toxic.

Some tips
on distinguishing science journalism from infotainment.

And. . .a tap-dancing seagull.

Wednesday Links

Wednesday Links

Here are some references to help you win at logic: The Skeptic’s Guide to the Universe explains how logic works and doesn’t work before delving into its top 20 logical fallacies – how to spot them and how to counter them. The Nizkor Project breaks them down by type, and you can search them by name. Logical Fallacies is an encyclopedic reference, a little more detailed than Nizkor, and an easier font and background than Skeptic’s Guide. Thou Shalt Not Commit Logical Fallacies is great if you’re a visual learner, with little icons for each individual fallacy. The Master List of Logical Fallacies is written for writers, has a few different names for some fallacies that you might not recognize, but is maybe a little easier to understand because there’s less Latin.

Speaking of fallacies, one of the big ones is the “teach both sides,” or “teach the controversy,” usually found regarding evolution. Dave Hone, in The Guardian blogs, shows how misleading this is with a specific case of a TV show that showed “both sides of the debate” regarding the evolution of birds. One side is represented by the majority of experts, the other by people who have an opinion.

Genetic research unearths a possible marker for prostate cancer, which may help us develop targeted treatments to cure it.

More on genes and cancer. . .apparently the genetic condition called Laron’s syndrome makes people’s bodies short, but their lives long. Somewhere in their genes, they’re resistant to growth hormones and resistant to cancer. Fascinating.

Phineas Gage is probably the best-known case of the effects of traumatic brain injury on behavior. New technology attempts to recreate the damage that was done by the railroad spike in his head in an effort to understand it better. Mindhacks isn’t sure he wants to know more, but shares it anyway.

Sometimes you need an outside perspective to see that an idea looks stupid. People in the UK think the NRA’s idea to put armed guards in schools is nuts. I think they’re right.

The Keystone pipeline could make this a scene anywhere along its entire length. Maybe that’s better than an ocean spill, but wouldn’t we rather avoid it in the first place if we can?

Rhinos are dangerous animals. Really dangerous. But how can you be scared of one that looks this cute?

Wednesday Links

Wednesday Links

Chiropractors playing to a parent’s deepest fear – SIDS. We don’t know what causes it, we know little about how to prevent it, but Chiropractors lay claim to secret knowledge and take advantage of new parents’ willingness to do anything for their children by lying to them.

Ed Yong tells an inspiring story of a triumph in genomic medicine. Lilly Grossman carries a gene mutation that fills her nights with shaking and seizures instead of sleep, but finding it delivers the treatment she needs to live an almost normal life. Grab your hankies.

This won’t make a lot of sense to many people, but an abstract that shows a possible neurobiological connection for skin picking and hair pulling (dermatillomania and trichitillomania) makes me think how nice it would be to eventually find a way to fix it.

Take this, people who think diet can prevent all disease. So there.

This may seem like a wonderful advancement in prosthetics, but can you say. . .mind control?!?!?

Recognize a pattern? Republican sticks to party platform, opposes gay marriage. Republican offspring comes out as gay. Republican weasels out of original stance.

I can’t say this where it’s appropriate, but you can tell when someone thinks he knows more than he actually does when he’s not even wrong. Unfortunately, the Dunning-Kruger effect means it will be impossible to educate him as to why this is so. He does not experience the discomfort of cognitive dissonance and learns only what strengthens his confirmation bias. Worse, this is willful ignorance and intellectual dishonesty. Rationalwiki is an appropriate source of information to reflect my repressed snarkiness. Enjoy.

Bookmark this site for when you need a good laugh or a healthy dose of schadenfreude. There is simply too much here for me to give it to you a bit at a time. Bask in its guanophrenic glory as it slowly loads the page bit by bit up to the top. If you really want to get in the spirit, go to the pantry and get some tinfoil to make yourself a party hat first.

AWWW!! ELEPHANT BAYBEEE!