When genes fight

For those of you just tuning in: on a genetic level, all parental investments in their offspring are equally valuable.  From the offspring’s perspective investing in them is two to four times as good as investing in their sibling (depending on if they’re half or full siblings).  The fight to get the amount of resources they think they deserve is parent-offspring conflict

One manifestation of parent offspring conflict is weaning conflict, where offspring would like to keep getting nutrients with no effort and their mom would really like them to go out and get a job.

But it can start before then.  Conflict over exactly how much nutrition a fetus should get may contribute to preeclampsia (high blood pressure during pregnancy) and insulin resistance (PDF).  This is not just about mothers not wanting to give up nutrients- more nutrition leads to larger babies, which is almost always good for the baby but kind of hard on the person forcing it out through their vagina.  There is even speculation that the human custom of making a thick uterine lining (nutritionally expensive) only to flush it away each month evolved as self defense against a placenta that would otherwise invade your uterus like ivy invades bricks.

This is your uterus on babies.
This is your uterus on babies.

Creepy, yes.  Abhorrent, at the level of individuals.  But totally logical and predictable from the level of a gene.

Kin Selection

The idea of kin selection was implicit in my post on haplodiploidy but let’s make it explicit.  The unit of selection is the gene, not the individual.  The individual is a co-operative venture by many genes to reproduce themselves [I attempted to explain why this was and it became 4 paragraphs on the origin of DNA, so let’s just take it as a given].  There’s no reason for genes to prefer directly reproducing themselves: if you can get more copies of yourself by helping someone else’s co-operative venture than your own, that’s a better investment.  Doing so is known as kin selection.

The most obvious example of this is parental investment in offspring.  Offspring aren’t you, but they have your genes.  For a diploid sexually reproducing organism, a given allele of yours has a 50% chance of being in your offspring via common descent (sharing an allele via coincidence doesn’t count for reasons we will get to).  But a full sibling is just as related to you as your child, so raising them is just as good.  The technical term for this is helpers at the nest*.  It’s especially likely when raising offspring is exceptionally costly and resources (e.g. territory) are very limited, so the choice is between raising siblings or nothing, rather than raise siblings or raise your own offspring.

As you might guess from the name, helping at the nest is most common in birds, but you do see it elsewhere. Golden Lion Tamarins live in groups of 2-8, but will usually have one, with a maximum of two, breeding females.  Females are unable to provide sufficiently for their offspring on their own.  They’re helped out by other group members, which are likely to be their own children, siblings, or sibling’s children.

Honestly I have no idea if that's a helper or the parent but it's adorable.
Honestly I have no idea if that’s a helper or a parent but it’s adorable.

Nest-helping may be at intermediate step between the “good luck, fuckers” school of parenting (technical term: r-strategist) and eusociality.  For example Carpenter Bees (carpenter is a genus, there are 500+ species within it) are usually solitary, but some build nests near each other in trypophobia-inducing pattern,. show specialization and cooperation between nesting adults (e.g. one guards all nests while others forage) , and daughters sometimes share a single nest with their mothers.

Don't trust pictures in nature articles.  I couldn't find a picture of cooperation so I used one of fighting.
Don’t trust pictures in nature articles. I couldn’t find a picture of cooperation so I used one of fighting.

One way to help your own siblings is to raise them, like helpers at the nest do.  Another is to free up parental energy by taking less for yourself.  From a genetic perspective, you should stop asking for things from your parents if the energy would benefit a full sibling twice as much, or a half sibling four times as much.  But from the parents perspective children are all equally valuable, so they will want to switch giving as soon as resources benefit one child more than another.  This is parent offspring conflict, as explained by noted evolutionary biologist Dylan Moran at 30:00 in this lecture:

More on parent offspring conflict tomorrow.

*Note: kin selection is not necessarily the only reward for helping to raise siblings; individuals may also learn parenting skills or give themselves a leg up claiming their parents’ stuff when they die.

Haplodiploidy

Let’s start way at the beginning.  All eukaryotic cells (which includes any multicellular organism) carry their DNA wrapped up in a chromosome

2000px-Chromosome.svg

In any given species the chromosomes are numbered, and chromsome N contains predictable information.  For example, the human chromosome 16 contains the DNA to alpha-globin, a component of hemoglobin, the thing that lets your red blood cells carry oxygen.  Some people have a variant in their alpha-globin genes that leads to sickle cell anemia.  It’s still chromosome 16.  The general location and form of the DNA that produces a protein is the gene, different variations are called alleles.  So technically it’s wrong to say “the gene for sickle cell”, you need to say “allele for sickle cell”, but everyone knows what you mean.

Many organisms contain more than one version of their chromosomes: the second (or more) chromosome has the same genes but different alleles (unless something goes weird, which does happen but we don’t have time to get into).  You are probably most familiar with the human chromosomes: 2 versions of 22 normal chromosomes, an X chromosome, and either an X or a Y chromosome, with Y chromosomes conferring maleness.    Having two versions of each chromosome is referred to as being diploid, and it’s not the only choice.  Certain sugar cane hybrids have as many as 12 copies of the same chromosome.  Some species show variation in ploidy between individuals.  This is more common in plants, which can self-fertilize, but is also seen in insects.  In humans individual chromosomes are occasionally doubled when they shouldn’t be: this causes death if it’s a big chromosome and things like Down’s Syndrome if it’s not.

Note that the Y chromosome does not contain all the information you need to be male: it releases the signals to be male, and numerous genes on multiple chromosomes respond accordingly.*   That’s not the only way to determine sex.  Birds, some fish, some reptiles, and a few others species use the ZW system, which is the same as XY except females are the one with the Y chromosome.  Many reptiles sex depends on the temperatures their egg experienced (and not every species responds to temperatures the same way).   We don’t know how sex is determined in the platypus, which, yeah, that’s about what I expect from the platypus.

Then it gets weird.  Fruit flies, and have the equivalent of X and Y chromosomes- but they have anywhere from one to four versons of sex chromosomes, and 2-4 versions of each non-sex chromosome (autosome). All autosomes have the same number of versions, but there may be a different number of sex chromosomes.  The sex of a fruit fly depends on the ratio between the # of autosome copies and sex chrosomsome copies.

But what I really want to talk about (600 words in) is haplodiploidy.  A haploid cell has only one version of each chromosome, a diploid two.  In haplodiploidy, females are diploid, and both male and female produce haploid gametes (egg and sperm).  Unfertilized eggs grown into males, and fertilized eggs grown into females- so females have twice as many chromosomes as their brothers.  Males have one grandfather and no father at all.

This has a couple of implications.  One, most deleterious recessive genes get weeded out right quick, because no male will produce them.  On the other hand, such a gene could persist if it boosted female reproduction sufficiently.  Second, females can reproduce without males, although they will produce only sons.  Which they can then mate with (and inbreeding isn’t nearly as dangerous as it is in diploid animals, because of the aforementioned filter on negative recessive genes), and produce daughters, so a single female can repopulate the planet.

Then there’s relatedness.  A human is 25% related to a half sibling (for any given gene there’s a 50% chance it came from the shared parent, and a 50% chance the parent passed it on to the sibling).  But a haplodiploid father passes on the same genes to every child, so each sibling is 50% related to each other through him.  If the siblings also share the same mother, they are 75% related to each other.  That is more related than they could be to their own offspring (50%).**

It was initially thought that this was why/how eusociality developed: it was literally more advantageous to raise sisters than daughters.  That’s not strictly true:  There are haplodiploids without eusociality, and strict diploids with eusociality.  Some  eusocial haplodiploid queens breed with multiple males, so their daughters are raising sisters only 25% related to them.  But eusociality is heavily overrepresented in haplodiploid animals, so it clearly affects the math.

*Fun fact: the signal for male development in utero is not exactly the same as the signal for male development at puberty, and it’s possible to be unable to produce the fetal signal but successfully produce the puberty signal, producing babies that are born with female external genitalia but grow a penis and testicles at puberty (nearly all of these children identify as men as adults).  This was common enough in certain villages in the Dominican Republic that they have a name for it, which translates to “penis at 12.”  It’s considered a joyous thing because sons are more valued than daughters.

**But aren’t their sons 100% related to them?  Yes.  But relatedness is not necessarily reciprocal.  A gene in a female has only a 50% chance of being in a given son, so she is only 50% related to him.

Review: Neanderthal Man

As a narrative about how science works, this is pretty strong.  I got it as part of my new policy of not reading emotionally intense books right before bed, and while it didn’t produce the post reading anxiety that, say, that book about slavery did, it was pretty exciting and pushed my bedtime back quite a bit.

The actual science, I’m not sure about.  He’s doing molecular biology without any background in basic bio, so he says things like “I didn’t know insects were animals.” on his first day as a zoology professor (he’s since realized his error) or “Can we really say they’re the same species just because they fertily interbreed.” in his book, on biology, that people paid him actual money to publish.  Yes, we can say that because that is exactly what species means.

I’m also a little confused by how they determined humans and neanderthals interbred.  It seems like they’re using the same data to calibrate the technique they’re using to sequence the DNA, the degradation rate of DNA, the contamination rate of the sample, when humans and neanderthals diverged, and when/how much they interbred.  He also doesn’t make a good distinction between when he’s talking about junk DNA (which is not subject to selection pressure, so is a pretty good molecular clock) and when he’s talking about genes (which is, and so it’s difficult to distinguish inheritance from the same source, interbreeding, and convergent evolution).

Lots of very smart people with much more information and training in this area than I have seem to be okay with his conclusions, so I assume this is one of those things where he is simplifying, and I know enough to know that he is missing something but not enough to fill in the gaps myself.  But if you are not in that uncanncy valley, it’s very well written and entertaining.

Loratadine for Allergies?

The Decision Tree casually describes loratadine (brand name: Claritin) as barely better than placebo for treating allergies.  This is news to me because Claritin was absolutely critical to me graduating middle school.  If I forgot to take it in the morning my mom had to drop it off at school by lunch.  Without it I slept 16 hours a day,* woken up only by hives that itched so intensely they burned.  This isn’t actually relevant to me now because my allergies were taken care of my unprocessed honey and moving, but I couldn’t believe something once so important was essentially a sugar pill. So I investigated.

First stop, Wikipedia, which definitely backed my claim that Claritin treated sneezing, runny nose, itchy or burning eyes, hives, and other skin allergies.  But of 19 citations, 5 were unavailable to me (either they were books or in languages I don’t read), 13 were on topics other than clinical efficacy (e.g. side effects or mechanism), and 1 had a sample size of 192 and was a comparison against another anti-histamine, with no placebo or no-treatment group.

So I checked google scholar, where I found numerous minuscule studies (n = 14, 7 treatment groups) in which loratadine was better than placebo but worse than other drugs in the same class.**  If that’s true, why did loratadine get so much more attention?  I looked up the other drugs, and it turns out that some of them (cetirizine/Zyrtec) had similar efficacy but came out later, and went over the counter later as well.  Others (Terfenadine/Seldane) had much uglier side effect profiles (e.g. cardiac arrythmia if you eat a grapefruit).  So Claritin’s advantage seems to be being the first drug to market that treated the problem with minimal side effects.  I also wonder if Decision Tree‘s author (Thomas Goetz) was looking at a particular symptom set?  For example, loratadine appears to do well as a treatment for hives but there are better options for hay fever.

Some people suggest that having multiple drugs with similar response rates in the same class on the market is some sort of failure.  They are wrong and they should feel wrong.  First, these drugs were developed in parallel by different companies. While all the ones we heard of worked out, very few chemicals that pharma companies research become prescribable drugs, and they can’t predict which ones will do so ahead of time.  What if McNeil stopped researching Zyrtec because Bayer was researching Claritin, and Claritin made you grow arms out of your face?  We’d have lost years of allergy relief.  Second, the fact that they had similar average efficacy and side effects doesn’t mean they have the same effect in every person.  People are squishy and they don’t make sense, and differing reactions to drugs is one of the milder ways this manifests.

*No, fatigue is not a normal symptom of allergies, but I got it most springs and it went away with anti-histamines, which is good enough for a field diagnosis of allergies.

**I also found a lot of studies detailing the effects of loratadine in conjunction with another drug, mostly montelukast, and abstracts that reported loratadine’s efficacy relative to older antihistamines but without absolute numbers.

Leptin: Catching Chemicals

Leptn is often considered the anti-ghrelin.    It is produced by fat cells to say “I exist and am full, you do not need to feed me.”  Animals with their leptin gene knocked out grow enormously fat.  This is a perfectly lovely story that can be conclusively proven by a picture of a fat rat.

Figure2diabetes
Bring me Solo and the wookie

If you do not find this story compelling, please consider that I also have a photo of a fat mouse.

Well, if it isn't Lone Star. And his sidekick, Puke
Well, if it isn’t Lone Star. And his sidekick, Puke

Are you convinced yet?  Look, I know last week I said all hormones are almost fractally complicated and anyone who says they completely understand one is lying, but that entry forever to write (thanks for publishing that a week early, wordpress), and this entry has pictures of obese rodents.  Surely you believe the rodents?

Original source: http://commons.wikimedia.org/wiki/File:Big_Fat_Red_Cat.jpg
If no, would a cat be sufficient?

*sigh* I’ve created a monster.

Like ghrelin, leptin is important to fetal lung development because, and I quote, “I don’t know stop asking me.”  Leptin is also produced by the ovaries, skeletal muscle, stomach (some cells produce both ghrelin and leptin), mammary epithelial cells, bone marrow, pituitary, liver, and of course adipose tissue.

Leptin stimulates ovulation and sperm production, which makes some evolutionary sense: getting pregnant when you don’t have the resources to carry it to term in a healthy way is extremely costly (men have to be nearly dying before they stop producing sperm entirely, but levels can drop incompletely before then).  This doesn’t explain why the ovaries (but not testicles) produce leptin, since they don’t have any independent information about fat stores.  This may be an example of an override (in which the ovaries decide they want a baby even though the rest of the body doesn’t believe it has enough fat), but the fact that I can come up with a clever anthropomorphization does not make an explanation legitimate.  You can sort of see why leptin facilitates the onset of puberty, since puberty takes a lot of energy.

What you can’t see is why, despite everything we know about pregnancy and eating, the placenta produces leptin. Excess amounts appear to cause hyperemesis gravidarum (extreme morning sickness aka Kate Middleton’s one weakness).

katemiddleton

High amounts of leptin appear to be good for your brain.  Just so story: brains are extraordinarily expensive, so if you don’t have sufficient savings your body turns on the dimmer switch.  They also have a long term protective effect against Alzheimers.  On the other hand, high levels of leptin alter the immune system in a way that encourages artery hardening.  I am way more afraid of living with Alzheimers than I am of dying of a heart attack, so I will count this as one point for fat.

Leptin’s overall effect on the immune system is complicated.  Leptin is an inflammatory agent, possibly to prevent damage from overreating as your body suddenly tries to shove extra calories that won’t fit in the white adipose tissue under the bed and in the coat closet (the organs).  Which may explain why ghrelin is an anti-inflammatory.  Leptin and ghrelin chose opposite powers and color schemes, like an early 90s superhero cartoon.

Or an early 90s cartoon
The safe represents the hypothalamus

Fatness in humans does not appear to be a problem of inadequate leptin production, and more leptin does not make people thinner.  Instead, it appears that the brains of obese individuals are less sensitive to leptin.  No one knows exactly why, but “crash dieting” is high on the list of suspects.  Two people with identical body compositions but different genes or life history may produce very different amounts of leptin, which means they may require very different behavior to stay the same weight, in ways we do not understand at all.  Which I could have told you before we went on this magical photographic tour of my childhood.  But now we know for sure, plus I learned that fetal lung development is creepily intertwined with food in a way no other organ is.  Let us go forth and use this new knowledge

The Rescue Rangers also want me to play video games.
The Rescue Rangers also want me to play video games.

Why Jezebel is Wrong that Cats Don’t Care About You.

Jezebel has a post titled “Why House Cats Generally Don’t Care (About You)“, in which they assert that cats don’t care about humans because they’re so close to wild cats.  Where do I start with this?

  1. The claim that domestic cats are closely related to wild cats is not backed up by numbers.  Jezebel claims ” house cats may not be that genetically different from wild cats”, citing sister site io9, which in turn cites a summary (warning: PDF) of the base article for its claim that the feline genome is “highly conserved.”  (Jezebel eventually links to the full article, but only the abstract is accessible)
    1. I’m not sure it’s actually wrong to describe an entire genome as highly conserved, but the term is usually applied to specific genes or even gene sequences, not entire genomes.
    2. You know what is a good system for measuring how different two things are?  Numbers.  For example: humans and common chimpanzees share 97% of their DNA.  Eyeballing it, it would not surprise me at all if domestic cats were more related to their ancestral wildcat than humans to chimpanzees.  I don’t see any numbers in either blog post or any of the article summaries I have access to.
  2. Despite numbers being excellent at measuring things, genetic similarity does not correlate very strongly with behavioral similarity.  For a fascinating example of see the fox domestication experiment, in researchers attempted to breed fur-farm foxes for tolerance of humans.  They succeeded in less than 40 years.  

     

     

    1. Domesticated foxes vary from undomesticated fur-farm foxes by only 40 genes.  They tragically don’t give a total gene count, but farm + domesticated foxes different from wild foxes by 2,700  genes, so 40 is almost 0%.  Nonetheless, undomesticated adult farm foxes will either bite your face off or cower from you, and domesticated ones want tummy rubs.

      .  We’ve had thousands of years with cats, we could make them want tummy rubs if we wanted.

  3. Which we have done.  Jezebel seems to be ignoring variation between breeds and individuals.  Certain breeds, like burmese, scottish fold, and Maine coon, really love and orient towards humans.  They don’t have dogs ability to read human facial expressions, but they do seek out their owners for attention, even when no food is on offer.  My cat loves tummy rubs and will fetch his favorite toy, although he has yet to realize people other than me can throw them.
  4. Meanwhile chow chows, one of the earliest dog breeds, possibly originally intended as food, are described as “cat like” because they’re so independent, and need extensive socialization to even tolerate strangers.
  5. Jezebel also comments on cats’ hunting behavior.  What they say is true, but it’s equally true of dogs: domestic and wild, feline or canine, animals have hunting behavior built in but need to be taught to eat what they kill.

And thus concludes your daily dose of Someone Is Wrong on the Internet