The human genetic casserole

HotdishI haven’t said much about this article in Science, Ancient DNA Links Native Americans With Europe, because it would be an understatement to say I’m digesting it. I would offer up a caution that using terms like “Europeans” and “East Asians” for populations which flourished ~25,000 years ago might be misleading. We are used to thinking of genetic distance in terms of space, but time is also a dimension to consider. Populations even without admixture or gene flow will have drifted in allele frequencies over so many generations.

But I have to admit that it seems more and more likely that most extant modern populations are combinations of lineages which diverged very early after the “Out of Africa” migration. We see this clearly with South Asians, and now Europeans and Native Americans. The Reich lab has also found evidence of admixture in in Australians. The closer we look, the more amalgamation we see between disparate lineages. Using the elements of the present to reconstruct the patterns of the past is going to be a more daunting task than most would have guessed.

Our forefathers were fierce & our foremothers were faithful

Credit: Chineeb
Credit: Chineeb
One of the peculiarities of human historical genetics is that people can simultaneously accept the existence of aggressive polygynous males such as Genghis Khan, and promiscuous females who give rise to the idea that 1 out of 10 children have an incorrect assigned paternity. I’ve mentioned the cuckoldry myth before. It is a common evolutionary myth; I’ve heard many biologists quote the 1 out of 10 number, and have often made myself obnoxious by pointing to the contradictory literature in this area. This isn’t to say that cuckoldry doesn’t exist. There’s certainly an evolutionary reason so many males engage in “mate guarding.” But you don’t need a high frequency of a trait to allow it to be selectively constrained. If it’s deleterious, then it will be driven down in frequency rather quickly. Whenever you get outbreaks of males who are sanguine about providing resources for offspring who are not their biological issue, natural selection will kick in and guarantee that this generous spirit toward their cheating partners and the delinquent cads does not persist.

Read More

Open Thread, 10/27/2013

I’ll be on the Kathleen Dunn Show on Monday, 2 to 3 PM Central Standard Time. You’ll be able to listen to the show after it airs on the website. It will be about my piece in Slate.

AJjacketI recently read Ancestral Journeys: The Peopling of Europe from the First Venturers to the Vikings by Jean Manco. You can find more information at her website, but I pretty much would recommend this book to all my non-scientist readers. I’d recommend it to many of the scientists too, if you are rather weak on archaeology, because that’s where Manco’s knowledge is really impressive. It’s not a perfect book, and I don’t agree with all the details, but it’s a very detailed, dense, and fast read.

There was a question below in regards to the Fast Company profile of 23andMe and what they’re trying to do. A major ethical issue brought up is whether it is acceptable to type children and disclose possible disease risk later on in life. As an extreme case, what if you find out that your child is going to develop a life threatening disease by the time they’re 40? My own perspective as a parent is that I’d like to know, and I’d probably want to tell my child as soon as I think they can handle it. The reason is simple: you base your life decisions on various aspects of life expectancy. People put things off, or forgo consumption, all the time.

Burning down the trees in historical population genetics

BurnTreephylogenetic tree is an essential tool in understanding the broad scope of natural history, placing particular lineages in specific evolutionary contexts of relatedness. These sorts of trees range from Ernst Haeckel’s classical attempt, depicting relationships which biologists derived from intuition within the framework of a grand evolutionary scheme, all the way down to modern methods implemented in software packages such as Mr. Bayes, which many frankly utilize in a “turnkey” manner. These trees are abstractions, in that they reduce down a wide range of phenomena into schematic representations which impart aspects of particular interest in a stylized form. This is important, because the actual nature of the phenomena being represented may be more complex than is being represented. A simple illustration of what I’m getting is clear when you look at the long history of phylogenetics and phylogeography utilizing mitochondrial DNA lineages (mtDNA). Because mtDNA is copious in comparison to nuclear DNA, it is easy to obtain. And, as there is no recombination and it is inherited in a haploid fashion (mother to daughter) it makes the inference of gene trees much easier. The key problem is that the genealogy of this particular sequence is used to infer aspects about population history, when they may not accurately represent the history of other regions of the genome very well. Different genes may have different histories.

Read More

The Roma have multitudes

Credit: Dbachmann
Credit: Dbachmann
Update: Turns out “Maria” is also an ethnic Roma.

There was a recent case in Ireland of a young Roma girl who was blonde haired and blue eyed being removed from her home, on the suspicion that she was not in fact the biological child of the presumed parents (who, like most Roma, are reportedly of dark complexion, hair, and eye). I even saw a report that a hospital was consulted on the probability of such an outcome, and they said it would be “extremely unusual”. It turns out that DNA tests confirmed that this girl was the biological child of the putative parents. And of course all this has be understood in light of the case of “Maria” in Greece; a little blonde girl who turned out not to be the biological child of the two Roma who claimed her as their daughter (it looks like there was welfare fraud in that case).

My initial response to the Irish case was that consultant should be fired, because in an admixed population like the Roma it shouldn’t be that unusual to have offspring who deviate a great deal from the parental phenotype. This prompted some interesting reactions. First, there were those who seem blissfully ignorant of the fact that the Roma are an admixed population. That’s easy enough to resolve, as there have been scientific papers published on this issue using genome-wide data. Second, there are claims that very small fraction of Roma have blonde hair and blue eyes (on the order of less than 1%). The latter may be a defensible claim, though not indisputably so.

Before we move on I have to clarify that there is a distinction between “Roma” and “Romani.” The latter refers broadly to the populations across Europe which were referred to as “Gypsy,” while the former denotes a set of populations with a center of distribution in Southeast Europe, in particular in the Balkans. In much of Northern and Western Europe there are now two populations of Romani with very distinct histories (and genetics): the Roma who have recently arrived from Southeast Europe, and the various non-Roma groups who have a very long history in their nations of residence (e.g., Finnish Kale).

In terms of various traits we know a fair amount about the genetics of pigmentation in humans. Though the fine grained individual predictive models are coarse, most of the genes which have large effects on population-scale differences are now well characterized. This allows me to produce a model which is reasonably plausible to give you an intuition for why brown-skinned populations can generate a wide range of outcomes in realized phenotype.

Imagine five loci rank-ordered in effect size, gene 1, gene 2, gene 3, gene 4, and gene 5. Each gene comes in two flavors, two alleles. One is a “dark” allele (produces dark pigmentation) and another is a “light” allele. From these you can have a distribution of complexion which is referred to as a “melanin index” (it’s dependent on reflectance). Imagine that you assume each allele at each gene exhibits a melanin index value like so in relation to the aggregate:

Gene 1 = 30, 2
Gene 2 = 15, 1
Gene 3 = 10, 1
Gene 4 = 5, 2
Gene 5 = 5, 0


Read More

The inferred distribution of grandparental contribution

How much of your genome do you inherit from a particular grandparent?

In my write up on variation in inheritance patterns for Slate last week I did not explore the likely quantitative distribution in any detail (frankly, I think that part is confused or muddled at best). My primary focus though was on the empirical reality of variation, which people utilizing personal genomic services will receive, perhaps to their surprise. But in part triggered by that Slate piece and follow-up discussions at Twitter with Michael Eisen, Graham Coop decided to crunch the numbers. More concretely he took the known patterns of recombination in the human genome (from a paper he co-authored, Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans), and input these values into a simulation which generated distributions of contribution from maternal and paternal grandparents, How much of your genome do you inherit from a particular grandparent?

Read More

Cognitive biases, not science, poses ethical dilemmas

A Chimera

Yesterday I pointed to an io9 post, These Unresolved Ethical Questions Are About to Get Real, on my Twitter feed. It’s interesting (that’s why I tweeted it!), but there were some aspects which I thought were specious, and reflect common intuitions and fears in the public. Two in particular I want to highlight.

First, “Is it okay to introduce non-human DNA in our genome?” The premise is false. A substantial proportion of the human genome is derived from viruses. Lateral gene transfer in complex organisms is not unknown, and may sometimes be quite functional (arguably endosymbiogenesis and mitochondria is the classic case, but that’s so far back in the past that people aren’t shocked by it). Second, the piece also asks if we “Should we biologically enhance non-human animals?” Last I checked selection was a biological process. Domestication events have radically changed many organisms. The io9 piece spends some time on the possible Uplift of other species, but as a matter of reality coexistence with humans tends to reduce the intelligence of domestic animals (they offload many tasks to us). The narrow exception though is the case of dogs. Yes, they are uniformly less intelligent than wolves, but excel at reading human social cues. We’ve modified them to be our perfect companion animals!

Read More

If these bones could talk

Credit: Thomas Roche
Credit: Thomas Roche

By now you have probably seen the articles about how a new skull has transformed our understanding of the human family tree. The original paper is at Science, A Complete Skull from Dmanisi, Georgia, and the Evolutionary Biology of Early Homo. More colorfully you might say that this publication burns down the “bushy” model of human origins, where you have a complex series of bifurcations and local regional diversity, and then rapid extinction with the rise of H. sapiens sapiens ~50,000 years ago. In general I’m more in agreement with those plant geneticists who are skeptical of excessive fixation on the concept of species, so this is not a shock to me. To me a species concept is not a thing, but an instrument to a thing (i.e., I’m in interested in population and phylogenetics). The reason these sorts of findings overturn the orthodoxy has more to do with human cognitive intuitions about why things are categorized, than the reality of how nature arranges itself.

Read More

A note on my piece in Slate

Credit: 50% to Razib
Most of you are probably aware that I have a piece that was just published in Slate today, Which Grandparent Are You Most Related to? I’m not used to writing articles for the general interest audience, so I really appreciate Laura Helmuth’s feedback. All errors and confusions in the piece are mine, and there remains one major issue which I did not correct or refine to my satisfaction in the final draft. Michael Eisen pointed out on Twitter that my use of the law of segregation to compute the probability of inheritance from a single grandparent (50% of the autosome vs. 25% as expected) is misleading. I did include a section on recombination in earlier drafts, but couldn’t find a way to elegantly write about crossing over at length without become turgid. In the end I thought my reference to recombination was clear enough to allow one to infer that the true probability was much lower (close to zero as Michael notes), all the while maintaining the illustrative power in relation to the segregation in meiosis of homologous chromosomes. I was wrong, and hopefully this is will serve as a lesson in terms of how to hone my skill at balancing between opaque oversimplification and excessive technical detail. The empirical result of variation across grandparents was probably sufficient in this case.