Relatedness is relative: How can I be 85% genetically similar to my mom, but only related to her by half?

First of all, no. I am not the lovechild of star-crossed siblings, or even cousins, or even second cousins. 

This is a gee-whiz kind of post. But the issues are not insignificant.

Hear me out with the background, first, before I get to the part where my eyes bug out of my head and I pull out my kid's Crayola box and start drawing.

If you've learned about sociobiology, or evolutionary psychology, or inclusive fitness, or kin selection, or the evolution of cooperation and even "altruism," or if you've read The Selfish Gene, or if you've been able to follow the debate about levels of selection (which you can peek at here)...

... then you've heard that you're related to your parents by 1/2, to your siblings by 1/2 as well, to your grandparents and grandchildren by 1/4, to your aunts and uncles and nieces and nephews by 1/4 as well, and to your first cousins by 1/8 and so on and so forth.  (Here's some more information.)

So, for example. For evolution (read: adaptationism) to explain how cooperative social behavior could be adaptive in the genetic sense, we use the following logic provided by Bill Hamilton, which became known as "Hamilton's Rule": 

The cost to your cooperation or your prosocial behavior (C) must be less than its benefit to you (B), reproductively speaking, relative to how genetically related (r) you are to the individual with whom you're cooperating. That could have come out smoother. Oh, here you go:

C < rB, or B > C/r

If you're helping out your identical genetic twin (r=1.0), then as long as the benefit to you is greater than the cost, it's adaptive.

C < B, or B > C

If you're helping out your daughter (r = 0.5) then as long as the benefit to you is greater than twice the cost, it's adaptive.

C < (1/2)B, or B > 2C

So already, the adaptive risk to helping out your daughter or your brother is quite higher. And it's even harder to justify the cooperation between individuals and their sibs' kids, and grandkids, especially ESPECIALLY non-kin. But, of course creatures do it! And so do we.

As relatedness gets more distant and distant, we go from 2 times the cost, to 4 times, 8 times, 16, 32, 64 etc... You can see why people like to say "the math falls away" or "drops off" at first or second cousins when they're explaining where the arbitrary line of genetic "kin" is drawn.  If you offer up a curious, "we're all related, we're all kin," someone out of this school of thought that's focused on explaining the evolution of and genes for social behavior may clue you in by circumscribing "kin" as the members of a group that are r = 1/8 or r = 1/16 but usually not less related than that.

This has long bothered me because we're all genetically related and so much cooperation beyond close kin is happening. And it's been hard for me, as someone who sees everything as connected, to read text after text supporting "kin selection" and "kin recognition" (knowing who to be kind to and who to avoid bleeping), to get past the fact that we're arbitrarily deciding what is "kin" and it seems to be for convenience. I'm not doubting that cooperation is important for evolutionary reasons. Quite the contrary! It's just that why is there so much math, based in so many potentially unnecessary assumptions about genes for behavior, gracing so many pages of scientific literature for explaining it or underscoring its importance? 

(It could just be that as an outsider and a non-expert I just don't understand enough of it and if I only did, I wouldn't be gracing this blog with my questions. But let's get back to my reason for posting anyway because it's potentially useful.)

Right. So. Even for folks who aren't part of evolution's academic endeavor, it's obvious to most that we're one half dad and one half mom. The sperm carries one half of a genome, the egg another, and together they make a whole genome which becomes the kid. Voila!

There's even an adorable "Biologist's Mother's Day" song about how we've got half our moms' genome... 

... but there's biology above and beyond the genes we get from mom (and not from dad). And that song is great for teaching us that the rest of the egg and the gestational experience in utero provide so much more to the development of the soon-to-be new human. So "slightly more than half of everything" is thanks to our mothers. Aw!

But, genetically, the mainstream idea is still that we're 50% our mom. 

I teach very basic genetics because I teach evolution and anthropology.And I'm not (usually) a dummy.* I get it. It's a fact! I'm half, genetically, my mom and I'm also half my dad. 

r = 0.5

Okay! But, given these facts about relatedness and how it's imagined in evolutionary biology, facts that I never ever questioned, I hope you can see why this report from 23andMe (personal genomics enterprise) blew my mind:

Percent similarity to Holly Dunsworth over 536070 SNPs (single nucleotide polymorphisms or, effectively/rather, a subset of known variants in the genome; Click on the image to enlarge).
I am 85% like my mom and I am at least 76% like my students and friends who are sharing with me on 23andMe. Names of comparisons have been redacted. As far as I know, this kind of report is no longer offered by 23andMe. I spat back in 2011/12 and the platform has evolved since.

Okay, first of all, it is a huge relief that, of all the people I'm sharing with on 23andMe, the one who squeezed me out of her body is the most genetically similar to me. Science works.

But that number there, with my mother, it is not 50%. It's quite a bit bigger than that. It says I'm over 85% the same as her.

What's more, I am also very similar to every single person I'm sharing with on the site, including example accounts from halfway around the world. Everyone is at least 60-ish% genetically similar to me, according to 23andMe. I know we're all "cousins," but my actual cousins are supposed to be 1/8th according to evolutionary biology. How can my mom be related to me by only one half? How can my actual cousins be only an eighth (which is 12.5%)? 

What is up with evolutionary biology and this whole "r" thing?

Hi. Here is where, if they weren't already, people just got really annoyed with me. Evolutionary biology's "relatedness" or "r" is not the same as genetic similarity like that reported by 23andMe.

Okay!

But why not? 

Let me help unpack the 85% genetic similarity with my mom. Remember, it's not because I'm inbred (which you have to take my word for, but notice that most everyone on there is over 70% genetically similar to me so...).

It's because my mom and dad, just like any two humans, share a lot in common genetically. Some of the alleles that I inherited from my dad are alleles that my mom inherited from her parents. So, not only is everything I got from her (50%) similar to her, but so are many of the parts that I got from my dad. 

Let me get out my kid's arts supplies.

Here is a pretty common view of relatedness, genetically. In our imagination, parents are not related (r = 0) which can lead our imagination to think that their alleles are distinct. Here there are four distinct alleles/variants that could be passed onto offspring, with each offspring only getting one from mom and one from dad. In this case, the sperm carrying the orange variant and the egg with the blue variant made the baby.

1. (Please, if you're horrified by the "r" business in these figures, read the post for explanation.)

But few genes have four known alleles, at least not four that exist at an appreciable frequency. Some could have three. What does that look like? 

The green allele doesn't exist in the next example. As a result of there being only three variants for this gene or locus, mom and dad must share at least one allele, minimum. That means, they look related and that means that, depending on which egg and sperm make the kid, the kid could be more related to mom than to dad. 

2. (Please, if you're horrified by the "r" business in these figures, read the post for explanation.)

Now here's where people who know more than I do about these things say that the kid is not more related to mom than dad because she got only one allele from mom and that keeps her at r = 0.5. 

Well, that's just insane. What does it matter whether she got the allele from mom or dad? I thought genes were selfish? (Sorry, for the outburst.)

Again, I realize I'm annoying people and probably much worse--like stomping all over theory and knowledge and science--by mixing up the different concepts of genetic similarity (e.g. 50%) with "r" (e.g. 0.5) and horribly misunderstanding all the nuance (and debate) about "r," but I'm doing it because I'm desperately trying to know why these two related ideas are, in fact, distinct. 

One last pathetic cartoon. 

In this third example, as is common in the genome, there are only two alleles/variants in existence (at an appreciable frequency, so not accounting for constant accumulation of de novo variation). An example of such a gene with only two known alleles is the "earwax gene" ABCC11 (there's a wet/waxy allele and dry/crumbly one). Here, the two alleles are orange and blue. Most humans in the species will have at least one allele in common with their mate for a gene with two alleles, and it's not because most humans are inbred, unless we want to redefine inbreeding to include very distant relatives (aside: which may be how the term is used by experts). 

3. (Please, if you're horrified by the "r" business in these figures, read the post for explanation.)

But as a result of the chance segregation of either the blue or orange allele into each of the gametes, two people with the same genotype can make a kid with the same genotype. 

And of course, making a kid with your same genotype is the only possible outcome if you and your mate are both homozygous (i.e. where both copies are of the same variant so that leaves no chance for variation in offspring unless there is a new mutation). 

So, I wandered a little bit away from my point with these drawings, but I had to because I wanted to get down from where my imagination has me (us?) with "r" versus how things really are with reproduction. We are baby-making with vastly similar genomes to ours, so we are making babies with vastly similar genomes to ours. 

So, I do see why biology says I'm related to my mom by one half. But, on the other hand, what does it matter if I got the thing I have in common with my mom from my mom or whether I got it from my dad? Because I got it. Period. It lives. Period. 

[Inserted graf January 20, '17] Saying it matters where I got the similarity to my mom keeps us at r = 0.5. Saying it matters only that I inherited DNA like hers keeps us always, all of us, at r > 0.5 with our parents and our kids because any two babymakers share much of their genome.

And the fact that this (see 2 and 3) happens so often is why I'm a lot more than 50% genetically like my mom, and the same can be said about my genetic similarity to my dad without him even spitting for 23andMe. 

So, here we are. I don't understand why our relatedness to one another, based on genetic similarity, is not "r."

I hope it's for really beautifully logical reasons and not something political. 

Because...

If "r" was defined by genetic similarity, then would cooperating with my 76% genetically similar students and friends be more adaptive than the credit I currently get from evolutionary biology for cooperating with my own flesh and blood son? 

If "r" was defined by genetic similarity, then could we use the power of math and theoretical biology to encourage broader cooperation among humans beyond their close kin? 

So many questions.

Maybe I should re-learn the math and learn all the other math.

Nah. Not myself. At least, it wouldn't come fast enough for my appetite. Maybe someone who already knows the math could leave a comment and we could go from there... 

And it would be worth it, you know, because despite my relatively weaker math skills, I bet we're more than 50% genetically similar.

*from 23andMe: "You have 321 Neanderthal variants. You have more Neanderthal variants than 96% of 23andMe customers."

Life in 'trans'-it: Why genomic causation is often so elusive

We are in a time when genes are in the daily news, with reports of how this gene or that gene is related to disease, evolution, race, ancestry, and even social behavior.  But what are 'genes', and what do they do?  This is so often presented--in classes, even at higher levels of education--as a simple story presenting genes as bits of DNA that code for a protein, and proteins the molecules that do the functions of life.  We are still heavily influenced by the pioneering work of Gregor Mendel, who did his famous experiments with peas more than 150 years ago.  So, we still think of genes as elements with one or more variant states in a population, transmitted from parents to offspring, which cause some trait (he studied traits like size, shape, or color in his pea plants to try use this fact to breed better agricultural crops).

Mendel's intentionally focused, single-cause approach opened the way for an understanding of the mechanisms of inheritance and enabled one of the most powerful research strategies in all of science. But the idea of one gene and one function is a 19th century legacy that has put a conceptual cage around our thinking ever since.  Mendelian inheritance and its terms (like dominance and recessiveness, and even some of his notation) are still around, and indeed it all is rather ubiquitous even at the university level.  But we now know better, and can do better, and the many discoveries of the last century in biology and genetics present us with many 'mysterious' facts, basically unanticipated by the long, persistent shadow of Mendel's well-chosen simplifications.  It requires some thinking outside the Mendelian box to understand what they might mean.  

The cis image of the world
DNA is located in the nucleus of our cells, but where does genetic function take place?  The usual Mendelian way of thinking is that the action occurs in a particular place in our DNA where a 'gene' is. The gene codes for protein and (usually) has nearby DNA sequences that regulate the gene's usage---turning on its expression by transcribing the gene into messengerRNA.  That is, the gene itself determines how it's used.  It's in a given place in our DNA, and the presence of a complex of regulatory proteins that attach to nearby sequence cause the gene to be transcribed into messenger RNA, which exits the nucleus and is in turn translated into an amino acid chain specified by the sequence.  The amino acid chain is then folded up into a functional protein.

This local, focal view of gene action is what is called a cis perspective.  The Latin origin has a meaning like 'right here', or 'on this side'.  The specifics of this process differ depending on the gene, as no two genes work exactly alike, but the variation in the details is not central to the main point here,  the widespread perception of genes  as modular, chromosomally local self-standing functional units.

But this common idea of how genes work is inaccurate--it's a fundamentally inaccurate way to understand genes and genomic function.

The fundamental nature of life in trans-it
DNA is itself essentially an inert molecule.  It doesn't do anything by itself.  In turn that means that each nucleotide, and that means each new mutational change, cannot be said to have a function or effect, or effect size, on its own.  It only has an effect in terms of its interactions with other aspects of the genome in the same cell, other materials in that cell, that cell in its respective organ and that organ in the organism as a whole, and indeed all of this in relation to environmental factors. While some gene-regulatory regions are near a coding gene, and act in cis, most function involves things elsewhere, on the same chromosome or on others.  This is the trans causal world of life, and it means we cannot really understand what's 'here' without knowing what's elsewhere.

Indeed even Darwinian evolution is fundamentally an ecological phenomenon--it's about organisms' resources, threats, mates, and so on, at any given time.  As well as luck, there may be many levels and aspects of life that are about competition for resources and so on, that are important to survival and reproduction.  But cooperating, in the sense of appropriate interaction, is by far the most prevalent, immediate, and vital aspect of life (Richard Dawkins' ideological 'selfish gene' excessive assertions notwithstanding).

Trans means cooperation in life and evolution
Trans interactions are just that: interactions.  That means multiple components working together, which involves the 'right' combinations in the 'right' time and the 'right' cellular place.  By 'right' I mean functionally viable.  During development and subsequent live, organisms require suitable expression patterns of genes and the dispersion and processing pattern of gene products.  If this combinatorial action--this cooperation--doesn't occur to a suitable degree, the organism fails and its reproduction is reduced.  The extent of this failure depends on the nature of the combinatorial action.

In this sense, trans interactions may be reproductively better or worse and that can be a form of natural selection, whose result is the 'better' (more viably successful) patterns proliferate.  But this does not require Darwinian selection among organisms competing for limited resource.  Genomic variants whose cooperative interactions do not function can lead to embryonic lethality, for example, which need have nothing whatever to do with competition, and certainly not with other organisms seeking mates, food, or safety.  Ineffective cooperation is an evolutionary factor not identical to natural selection in its mechanism, but with similarly 'adaptive' effects.

In our view, cooperation based on trans interactions is more important, more prevalent, and more fundamental than Darwinian natural selection (as we write in our book The Mermaid's Tale).  Interactions that are successful become increasingly installed in the life history of organisms ('canalized' to use CH Waddington's venerable term for it), and this constrains the way and perhaps the rate at which evolution can occur.  This is neither heresy nor surprise.  For example, genes present today are the descendants of 4 billion years of evolutionary history, and most are used in multiple ways in the organism (at least in complex multicellular organisms; we don't know how true this is of simple or single-celled species).  They are less likely to suffer mutational change without serious effect, mainly negative. This is a very long-established idea, and is clearly supported by the high degree of sequence conservation of genes in genomes.

Genomewide mapping of most traits identifies many different genome regions that can statistically affect a trait's presence or measure.  But mapping rarely identifies coding regions.  Most 'hits' are in regulatory regions or regions with other (usually unknown) function.

This should surprise no one.  First, as noted above, 'genes' (protein coding regions) are largely of evolutionary long standing and embedded in interaction patterns usually in multiple contexts (they are 'pleiotropic'), so the coding parts are harder than regulatory parts to modify viably by mutation. It is empirically much more likely that their expression patterns can be varied.  Second, every gene is a complex of many different components (protein code, splice and polyadenylation signals--where the required AAAAA... tail of a mRNA molecule is attached--promoter sites, enhancer sites, and so on). Each of these is mutable in principle, and ample evidence shows that regulatory regions are especially so.  And each transcription factor or other gene product that is needed to activate a given gene (that is, the tens of proteins and their DNA binding sites that must assemble to cause a nearby gene  to be expressed) is itself a gene with all the same sort of complex modular structures.  RNA has to be processed, transported and translated by factors that, again, are potentially mutable.  And so on.  And then most final functions, physiological, developmental, metabolic, or physical are the result of complex processes over time, involving many genes and systems.

In fact, in recognition of biological complexity, many investigators suggest that the proper level of analysis should be of systems, that is, organized pathways of interaction that bring about some end result.  Gene regulation, physiology and metabolism, and so on, represent such entities.  The 'emergence' of the result cannot be predicted by listing the individual contributing elements, in the same sense that the effect of a new mutational change cannot be understood without considering its context.  However, systems themselves have overlap, redundancy, and elements that contributed in different systems at different times, and many systems may themselves interact in what one might call hyper-systems for a result--like you--to come about.  Analyzing emergent systems is at present an active but in many ways immature endeavor, because we still probably don't have adequate understanding, or perhaps not even adequate technology for the job.  But it's important that people are considering the trans world in this and other ways.

Causal complexity is predictable, and what we expect is what we see
Causation in life is fundamentally about cooperation which is about trans interactions.  Since cells are isolated from each other, so they can sense their own environments and respond to them, they actively signal to each other and a major way gene expression is regulated is through complex signal sending and receiving mechanisms.  'Signals' can mean gene-coded proteins secreted from cells, or the detection by cells of ions or other chemicals in their environment, and so on.  Signaling and responding to environmental conditions involves large numbers of genes and their regulation in time and space.  Most genes, in fact, have such cooperative, communicative function.

In turn, this implies that traits have many contributing genes, and their modular coding and regulatory sequences (and other forms of genome function, such as packaging and many different types of RNA), and each of these is potentially mutable and potentially variable within and between samples, populations, and species.  The result is the high level of causal complexity that is being so clearly documented.  A very large amount of viable contributing variation can be expected, if the individual variants have small effect.  The trait itself must be viable, but viability can coexist with large amounts of variation in the hundreds of contributing components.  This is what GWAS consistently finds, and is wholly consistent with how evolution works.

Life is complex in these ways in very understandable (and predictable) ways.  Enumeration of causes or even defining 'causes' are often  fool's errands because different variants in different genome regions in different samples and populations are to be expected.

It's a highly cooperative trans world out there!

And there will be humans no more? A review-ish of Greg Graffin's "Population Wars"

Perhaps best known as the leader of Bad Religion, Greg Graffin is also an evolution scholar. His latest book, Population Wars, is out today. 

I was hooked by the description that this is a "paradigm-shifting" book about human behavior, particularly for readers of Dawkins, Diamond, and Wilson. I was surprised at how heavily autobiographical it is throughout. But memoirs do make a lot of sense, given the many fans who are bound to read it, and given how the argument takes shape by the end. 

Graffin is appealing to our inner humans, but without appealing to our inner saps. If I had to sum up the book in one phrase, I'd say it's the least sentimental argument for saving humankind from extinction that you'll ever read. 

That's meant to be entirely neutral, but I don't think I can convey this next thing neutrally: 

I wouldn't have finished reading my advance copy of Population Wars if the publisher hadn't offered me a Q&A with the rockstar.

It wasn't because of his voice. I was thrilled when the first few pages beat just like Bad Religion when the volume's right. 

It was because of the content. I'm not one to throw many punches, let alone at members of my own tribe of evolutionary scientists-slash-authors. But I share this awkward fact (that the only thing that kept me reading this book was my eventual interview with a rockstar) for two reasons: 

Graffin can handle it. And, my experience taught me an important lesson. Because I stuck it out and read through the many pages of cyanobacteria, and the many, many pages of Iroquois history, I was reminded of the importance of learning what we're not necessarily very interested in learning--ever, or at a given moment, or from a particular human's perspective, or whatever. 

Population Wars didn't just teach me new things about natural history,history, and environmentalism, it incidentally taught me something bigger that I think I lost my grip on. It reminded me why we read books.

**

Books. Neatly stacked and bound piles of paper. This is where so many humans pour our hearts and souls. Whatever one thinks of Graffin's book, it's his blood and guts expertly smeared into teeny tiny perfectly discernible shapes. And you can feel how he honestly believes that humans can figure out a way to prevent our future extinction. That's utterly beautiful even if you don't see things that way. It's there for readers if they stick it out, turn each of those pages, and make it to the end where they can meditate over this human's heart and soul at once. 

When we're finished reading even the best books, the books that light us up from head to toe, we merely shut them and shelve them. CDs of music too. 

We've been married for over seven years and just last week I hear Kevin's "Rockers Galore" for the very first time. It's like a dream mix-tape of The Clash with interviews and it's my new favorite album. It's got Joe Strummer explaining what he was trying to say in Rock the Casbah: "There's no tenderness or humanity in fanaticism." 

That fleck of gold was just crammed into a cabinet this whole fucking time? That one sentence that elevates an already great song into the outer dimensions of the rock'n'roll-sphere was hiding in plain sight inside my own fucking house? 

CDs. Books. Even when they're not earth-moving, they contain more human creative and emotional energy than we deserve. But the ones who write them believe that we deserve it, which makes them even more magical. When we leave CDs and books sitting there, unexplored, we're failing humanity.

Population Wars charges us to find the humanity within ourselves to collaborate, globally, as a species to clean up and preserve our planet. Graffin describes how someone can see all of history through an evolutionary lens. His aim is to spread this worldview because it's this perspective, over common ancestry and deep time, that literally unites us as a species, even if we are divided culturally. Unfortunately, saving the planet is too big a job for anything less than all of us. Graffin's book is one voice toward our unification in the face of all the fanaticism.  

**

This is the first but won’t be the last time I write about the dinner I had with an astronaut. One of the small group of us, one of us who hadn’t walked on the moon, seemed desperate to get an inspired nugget of Truth out of the one man who had. He certainly was a remarkable human, but he clearly wasn’t supernatural. His body language and his seamless diversions showed he was as skilled at avoiding sentimentality as he was oxygen depletion.

In the presence of astronauts and other rockstars people want to have their hearts melted or their minds blown. They want to transcend. To quote Twitter: they want all the feels. When they’re not preoccupied with selfies, they’re begging rockstars for God and they expect to get it. Even in someone’s kitchen, over a casserole and some beers.  Even when they’re hardly fans of Bad Religion and they read its leader’s evolution book? I hope not. I think no one who picks up Population Wars, especially Bad Religion fans, is going to expect kumbaya. Yet, tree-hugging is something for Grateful Dead shows, not punk ones.

Graffin's argument isn't to save the planet for our babies or the polar bears', it's to save the planet because we can. Let's make it our moonshot. Let's boldly go, together, globally, here on Earth. 

That thing that we don't have that could unite us while give us purpose as individuals? That thing that Eggers' protagonist desperately wants? That thing Jon Stewart always talked about? That thing that binds us together with a goal? That thing is saving the species by saving the planet.

And if you're going to save the planet, you've got to learn about things that might not rock you to your core, things that might require more stubbornness than anything to hold your attention. I didn't want to read about Graffin's cyanobacteria. I even got angry about it, but if we're to make a dent in saving the planet, we should be reading about such tedious things. 

Point blank: We humans should be reading as much as we can, whatever we can get our hands on, and without a carrot dangling at the end of the book, without the promise of an interview with a rockstar. 

Because sharing our unique human experiences with one another unites us as humans. 

And also because rockstars go on tour. When you're all done reading and you write to the publicist to say, This is an important book, thank you for sending it to me. I want to write about it. Please set up a Q&A and please send the music that accompanies the book... She is likely to respond with an apology (and without the music too).  

So lessons learned! I read Population Wars and all I got was one brilliant human's heart and soul, one human's bold and hopeful vision for our species.  

**

Questions for Dr. Graffin

1. Is Population Wars punk rock?
2. Both perpetual mutation as well as genetic drift are fundamental to how I have come to understand natural selection as being much weaker than many still believe it to be. However, you have come to this seemingly same conclusion about natural selection without genetic drift and without much consideration of perpetual mutation. Can you help us understand how you did this? And can you explain why you left genetic drift out of your book?
3. I am drawn to discussions of free will, but it's hard for me to reconcile your argument that it does not exist with the goal of your book urging humankind to save the planet and ourselves. If there is no free will, how will your book's will be done?
4. What do you want readers to do after reading your book? I'm thinking specifically of the readers who cannot afford to emulate you by building an eco-friendly home and turning down big financial offers from natural gas companies. The book demonstrates your evolutionary worldview, but does not contain many directives. What can we do toward your goal of saving the planet and the species?
5. How do we join together as a species to accomplish anything together when there's such massive inequality?