Saturday, April 23, 2016

From the genetics of dog breeds to stress and reproduction

The other morning I was talking to my husband in bed in an attempt to help him wake up.

Me: So I ran into our friend who walks those three goldens separately yesterday and we had a nice conversation. She said she’d read my blog and had a dog genetics question for me.

Him: mmmppphh

Me: She said she’d heard that 1% of dog genes account for all the differences between breeds and asked me if it was true. I pointed out that 1% of 20,000 is still a lot of genes, and also explained that it's really hard to use statistics like that to describe genomic differences, because you can measure those differences in so many different ways.

Him: Did you tell her that humans and chips are 98% similar genetically?

Me: Yes I did.

Him: But I’ve been seeing that for at least 10, maybe 20 years. Is it still true?

I consulted the internet on my phone.

Me: Let's see... The Smithsonian Institute says we're 1.2% different from them. I think I'll skip this link to the Institute for Creation Research -- is that really the second hit on “human chimp genetic similarity”?! Ah, Wikipedia gives more information: “The alignable sequences within genomes of humans and chimpanzees differ by about 35 million single-nucleotide substitutions. Additionally about 3% of the complete genomes differ by deletions, insertions and duplications. Since mutation rate is relatively constant, roughly one half of these changes occurred in the human lineage.” Well, that’s not true.

Him: What?

Me: Mutation rate isn’t constant.

Him: It’s not?

Me: Well it is closer to constant in specific areas, like parts of the mitochondrial DNA, which we like to use as clocks. But over the whole genome, which is what they're talking about here, no. Different areas evolve at different rates. There are hotspots that go faster. And then the whole species might change faster when its environment suddenly changes. Like if you're in a lovely sunny valley and you're well adapted to it and then suddenly an Ice Age starts and your valley fills with ice and you suddenly have intense selection pressure to change your coat length and thickness and your diet and things like that. The stress itself can change your mutation rate.

Him: Stress can’t change your mutation rate! How would that even work? If a female is stressed, it’s too late, her eggs are already made.

Me: Her grandkids then? Or only sperm have more mutations? Hmm, that’s good point.

I consult the internet again. I find and discard an article about yeast evolving more quickly under stressful conditions. Yeast don't make eggs or sperm as part of their reproductive process.

Me: Here you go. Flies. Close enough to mammals for you? Stress does cause flies to have offspring with more mutations. It makes sense because if you’re stressed, it means you're probably not well adapted to your environment, so you should do the random shuffle with your kids’ genetics in the hopes that something, anything, different will give them a better shot. Mostly they’ll be worse off, but at that point it’s worth if it a few are better off and can pass on those genes.

Him: But how does it work with female flies having already made their eggs before they’re stressed?

Me: I dunno... Hang on... Here we are. OK, so the researchers mutated the males, their sperm.

The reason the researchers mutated the males has to do with how DNA is fixed in male and female fruit flies. There is almost no DNA repair in sperm. But the egg can repair DNA in any sperm that fertilizes it.

So the researchers were basically asking how much of the mutated DNA from the male could slip through the repair processes in the egg. The answer was that eggs from stressed females let a lot more mutations through.

Why would stressed female eggs not fix DNA as well? Probably because fixing DNA perfectly costs lots of energy. And these stressed females may not have had enough energy to spare.

There are two different kinds of DNA repair out there. The one that fixes the DNA perfectly costs a lot of energy. The other kind gets rid of any gross problems but leaves errors behind. This costs less energy but leads to more mutations.

The idea is that stressed females can't afford to use the perfect DNA repair system. So they use the other one. Their kids survive but they have more mutations.

—Stanford at the Tech, Understanding Genetics
 Me: Oh crap now I’m late to take Jack to physical therapy.

...Kind of makes you wonder about puppies conceived in puppy mills or animals conceived in hoarding situations, doesn’t it? Might they have more mutations than animals conceived in less stressful environments?


  1. I think they've looked into this in humans as well. The idea that stress in parents can affect genetics - even to grand-children was covered in some article IIRC. There was a discussion about the long term effects of WWII.

  2. Yes, here it is:

    1. Yeah, good point. There's been a lot of work on behavioral and metabolic changes in humans who were born after trauma to their parents. None of that has been linked to mutations, though; it mostly has been associated with different fetal development in utero due to (presumably) stress hormones from mom. It's been hard to do the mutation part of these studies in humans, lots easier in flies and yeast! If only we slowpoke humans had a few hundred babies at a time, things would be easier.

  3. When they talk about mutation rate being constant aren't they referring to the neutral mutation rate? Meaning the mutations that don't make a difference to natural selection either way. Also I just watched a documentary on Curiositystream that was about how epigenetic changes can be passed on just like genetic ones, they proved it up to 16 generations in a plant!

    1. So these molecular clocks that are supposed to depend on a mutation rate in areas that are not under selection -- I'm arguing in this post that these clocks are flawed and that I'm not convinced any areas of the genome (even those not under selection) have a steady mutation rate over millions of years. Some people disagree with me on this!

    2. "Him: Stress can’t change your mutation rate! How would that even work? If a female is stressed, it’s too late, her eggs are already made.

      Me: Her grandkids then? Or only sperm have more mutations? Hmm, that’s good point." DOES change the eggs because of my favorite thing in all of genetics: epigenetics. This is the study you're looking for (in people):

      Basically they study all sorts of things in the children of people who were of child bearing age during a famine. It turns out that stress changes the epigenentics. And it does happen to the eggs. It, in fact, is also caused even due to the medium that embryos used for artificial insemination are cooked up in and in premature babies.

      Stress alters the genetic makeup in the eggs of the women it effects. And not just her eggs, but really young embryos as well. It's frikkin *fascinating*, because I think that epigenetics is the thing that lets a species react to their environments quicker than you might otherwise expect on an evolutionary scale.

    3. Epigenetics are one of my favorite things too! (But I was talking about mutations here, which are different from epigenetics.)

  4. Do you suppose that if a pregnant dog were taken from a stressful environment to a non-stressful environment early enough in a pregnancy the full DNA repair would be triggered? I know of several rescues that pull pregnant dogs from shelters and work very hard to provide a calm environment for the Mom, and good socialization for the puppies...

    1. Any mutations introduced into the fetuses would be introduced when the eggs and sperm are made. Mom makes her eggs when SHE is a fetus so that ship has well sailed by the time she's pregnant (though you might worry about the eggs her fetuses are making). However:

      a) We have no real idea how much stress actually in the real world affects pregnant shelter dogs, so no idea if increased DNA mutations are even something to worry about.

      b) Nevertheless I strongly support getting pregnant dogs out of the shelter as soon as possible. We don't know when and how stress affects the fetus but we do know it does so in lots of ways, not just their DNA as discussed here but their brain development. Don't know when's the most important time to get them out, so get them out as early as possible!

      So good for those rescue groups. That's important work.