I really love the fact that I live in the early 21st century for a host of reasons. That being said, one aspect that’s certainly true is that when it comes to charismatic natural variety and geography there are very few “blank spots” on the map. You can get a sense of what I’m talking about if you browse National Geographic from the early 20th century. Most of the map had been filled in, but there were still nooks and crannies waiting to be illuminated. So I always find stories like this interesting, because they capture a sliver of the wonder that once was so commonplace, Snow Leopard Population Discovered in Afghanistan:
The Wildlife Conservation Society has discovered a surprisingly healthy population of rare snow leopards living in the mountainous reaches of northeastern Afghanistan’s Wakhan Corridor, according to a new study.
I’ve been taking about ‘meat things’ for nearly 10 years, so I was really excited by the new Michael Specter piece in The New Yorker about artificially grown meat, Test-tube Burgers. You can’t read most of it online, so I want to copy this small section:
…One study, completed last year by researchers at Oxford and the University of Amsterdam, reported that the production of cultured meat could consume roughly half the energy and occupy just two percent of the land now devoted to the world’s meat industry….
I say real factories because we are all aware I assume by this point of the nature of ‘factory farming’. But mass production of animal stock is an ad hoc kludge. Domesticated animals have been bred for meat production, but they remain organisms with all the range of activities and ends which the term ‘organism’ entails. Raising raw tissue in cultures may seem ‘yucky,’ a point Specter covers in assessing the reaction of some environmentalists and animal-rights activists who don’t seem as excited by the shift from conventional livestock raising to growing tissue as one would expect if they ran the numbers, but it is probably inevitable if it is feasible. The article makes the point that most of the focus on this area seems to be in the Netherlands, but thank god the Chinese are paying attention to this!
On DNA Day, 23 and Me had a sale on their personal genomics service. They’d do their standard scan of your genome for free, as long as you paid for a year’s worth of their online subscription service.
For the price (nearly free up front, and a modest cost for the online community provided), my wife and I jumped on the deal. Since I got the results back two weeks ago, I’ve been exploring not only the services and information provided by 23 and Me, but the various other tools that individuals have started producing to help analyze and investigate this insight into my ubiquitous but invisible DNA.
My genome, for instance, revealed a genetic predisposition towards late-onset Alzheimers. The odds of getting Alzheimers are still quite small, but elevated because of this particular mutation to the APOE4 gene. This wasn’t a total surprise, given my family history, and as a healthy, young guy with a background in biology and biostatistics, it wasn’t hard for me to put that information into a context and move on. Down the road, I’ll probably keep an eye out for new research on Alzheimers medicines and look into tools for early detection, but I’m not going to kill myself if I forget my keys. (Thanks to the federal Genetic Information Nondiscrimination Act and the Affordable Care Act’s prohibition on “pre-existing conditions” – not to mention the inherent uncertainties in translating this genetic result to a specific outcome – I’m not especially worried about discussing that result in public)
We need to demystify DNA. It’s pretty obvious to me that people perceive genetics to be in the domain of magic, when in reality it manifests itself in the banal realities of correlations within the family, which we’re intuitively aware of. But Josh’s post is more than just personal, he reviews the book Biopunk: DIY Scientists Hack the Software of Life:
The title above basically describes the message of evolutionary biologist Mike Lynch from what I can gather. His basic argument is outlined in long form in The Origins of Genome Architecture, though the outline of the thesis is evident over 10 years back (see Preservation of Duplicate Genes by Complementary, Degenerative Mutations). Verbally I think the easiest way to explain Lynch’s framework is that in species with small effective population sizes the creativity of stochastic forces in generating non-adaptive structure and complexity tends to overwhelm the power of natural selection to prune this tendency toward baroque. I reviewed a paper last year which argued that Lynch’s observation of an inverse relation between effective population and genome size was an artifact, that once you controlled for phylogenetic history it disappeared. Suffice it to say this is an area of dispute and active research, so we shouldn’t take any individual’s word for it. This is science on the broadest canvas. Extraordinary general claims need to backed by a generation of publication I’d think.
Lynch is now a co-author on a new letter to Nature (which is open access, so read it!), Non-adaptive origins of interactome complexity. Imagine if you took biochemistry, specifically the nearly impenetrable language of protein interactions, and crossed it with evolutionary genomics. This is what you’d get.
John Hawks and Jerry Coyne are mooting the ‘species concepts’ debate, with particular focus on recent human origins (specifically, the relationship of modern humans to Neandertals and Denisovans). Coyne, who coauthored the book Speciation and remains preoccupied with the issue in his academic work, knows of what he speaks. And of course he wouldn’t think that the discussion of species, how to delineate them, and what they are, is a sterile exercise. He has chosen to allocate a significant portion of his life to the topic. I think very few would disagree with Coyne when he contends that “Species are not arbitrary divisions of an organic continuum.” If there is one taxonomic category which has a concrete basis in reality, that would seem to be species. But, I would observe that I’m not sure that species are necessarily so clear and distinct. After all, we know that there is here and there, but where does here end, and there begin?
I’m of a reminded of the classic Zeno’s paradox:
Rosie Redfield has a “must read” post, Arsenic-associated bacteria (NASA’s claims). I won’t excerpt it, read the whole thing. To me it is very interesting that many pieces of her critique are ones I’ve encountered in emails or Facebook postings. She stitches them together into a coherent whole. She’ll be writing a letter to Science. Hopefully they’ll publish it. Even if you don’t have a deep background in microbiology and biochemistry I think it was clear that the authors had jumped to some inferences too quickly.
(Acknowledgement, John Hawks)
Update: Also, Arsenate-based DNA: a big idea with big holes:
So the Sargasso Sea tells us that some bacteria are capable of making DNA at very low phosphate concentrations. The most plausible explanation is that the bacterium GFAJ-1 can make normal DNA at micromolar phosphate concentrations, and that it also has the ability to tolerate very high arsenate concentrations.
This seems like the “boring,” but most plausible, explanation.
Update II: David Dobbs reviews the journalistic response. I think that people who write about science were in a bind because of the structural problems that David points out. When I first skimmed the paper it seemed to claim too much, but I had to keep in mind that it got through peer review. On the other hand as I stated once scientists in a position to critique on a genuinely technical dimension started complaining really loudly on social networking, that changed my own perception really quickly.
John Hawks, Genomes unzipped, unzipped:
What I wonder is, how much will personal genomics be like nude beaches? I mean, it’s been a long time since the first nude beaches, but most people don’t take advantage of the opportunity. Clearly, there’s variation in different countries! But most people neither feel compelled to see others’ data nor feel comfortable sharing their own.
Well, they used the word unzipped, not me!
Obviously John had his tongue-firmly-planted-in-cheek, but I have wondered about this. How deep is the impact of personal genomics going to be for individuals? If a person gets their genome sequenced and has a list of odds ratios in front of them are they going to bone up on the statistical genetic subtleties of the face value?
That is where genetic counselors come in. The necessity of interpretative experts highlights the difference between nude beaches and personal genomics: personal genomics has more potential societal impact. I know of the nudist/naturist phenomenon only tangentially, but it strikes me as similar to the broader New Age health movement. The focus is on individual health returns. A colon cleanse simply does not have much of broader social effect. Yes, lest my nudist readers strike me down I do understand that there are purported positive social externalities, but set next to personal genomics nudism still strikes me as a fundamentally more individual activity whose benefits redound to the naked individuals, and not the broader clothed society. It does not pick my pocket nor break my leg if my neighbor is a weekend nudist. It is of no concern of mine (in contrast, my experience with public nudity is that it is generally disruptive when unexpected).
Last month in Nature Reviews Genetics there was a paper, Measuring selection in contemporary human populations, which reviewed data from various surveys in an attempt to adduce the current trajectory of human evolution. The review didn’t find anything revolutionary, but it was interesting to see where we’re at. If you read this weblog you probably accept a priori that it’s highly unlikely that evolution “has stopped” because infant mortality has declined sharply across developed, and developing, nations. Evolution understood as change in gene frequencies will continue because there will be sample variance in the proportions of given alleles from generation to generation. But more interestingly adaptive evolution driven by change in mean values of heritable phenotypes through natural selection will also continue, assuming:
1) There is variance in reproductive fitness
2) That that variance is correlated with a phenotype
3) That those phenotypes are at all heritable. In other words, phenotypic variation tracks genotypic variation
Obviously there is variance in reproductive fitness. Additionally, most people have the intuition that particular traits are correlated with fecundity, whether it be social-cultural identities, or personality characteristics. The main issue is probably #3. It is a robust finding for example that in developed societies the religious tend to have more children than the irreligious. If there is an innate predisposition to religiosity, and there is some research which suggests modest heritability, then all things being equal the population would presumably be shifting toward greater innate predisposition toward religion as time passes. I do believe religiosity is heritable to some extent. More precisely I think there are particular psychological traits which make supernatural claims more plausible for some than others, and, those traits themselves are partially determined by biology. But obviously even if we think that religious inclination is partially heritable in a biological sense, it is also heritable in the familial sense of values passed from one generation to the next, and in a broader cultural context of norms imposed from on high. In other words, when it comes to these sorts of phenotypic analyses we shouldn’t get too carried away with clean genetic logics. In Shall the Religious Inherit the Earth? Eric Kaufmann notes that it is in the most secular nations that the fertility gap between the religious and irreligious is greatest, and therefore selection for religiosity would be strongest in nations such as Sweden, not Saudi Arabia. But as a practical matter biologically driven shifts in trait value in this case pales in comparison to the effect of strong cultural norms for religiosity.
Below are two of the topline tables which show the traits which are currently subject to natural selection. A + sign indicates that there is natural selection for higher values of the trait, and a – sign the inverse. An s indicates stabilizing selection, which tells you that median values have higher fitnesses than the extremes. The number of stars is proportional to statistical significance.
A month ago I pointed to a short communication in Nature Genetics which highlighted differences in the patterns of variation between the X chromosome and the autosome. I thought it would be of interest to revisit this, because it’s a relatively short piece with precise and crisp results which we can ruminate upon.
Sometimes there is a disjunction between how evolutionary biologists and molecular biologists use terms like “gene.” The issue is explored in depth in Andrew Brown’s The Darwin Wars. Brown observes that one of the problems with Richard Dawkins’ style of exposition is that it did not translate well to the American context. He spoke of genes as units of analysis, from which logical inferences could be made. This was the classical Oxford style of evolutionary biology which Ernst Mayr objected to. In contrast American biologists were used to thinking of genes in more concrete biophysical terms, and tended to miss the theoretical context which Dawkins was alluding to in his arguments. In Dawkins’ defense, it must be remembered that the gene does have its origins as an abstract entity whose biophysical substrate, DNA, was not known for decades. In my post Simple rules for inclusive fitness I outlined a paper which is very much in keeping with the analytic tradition. Start with an abstract model and allow the chain of inferences to be made, and see where it takes you.
There is a new paper in Nature which is a full frontal attack on the utility of William D. Hamilton’s inclusive fitness framework in explaining eusociality. Martin A. Nowak, Corina E. Tarnita, & Edward O. Wilson are the authors. Wilson is famous in large part for his authorship of Sociobiology: The New Synthesis, and is arguably the doyen of American organismic biology. He is both an active scientist, and, a premier public intellectual. So with that in mind, I notice that Dienekes Pontikos alludes to “E.O. Wilson’s change of mind about group selection.” This is conventional wisdom, but it is I think wrong (though from what I can tell Wilson has not done much to disabuse the press of the notion). In Defenders of the Truth Ullica Segerstrale notes that Wilson did not expunge group selection thinking even in Sociobiology. In Evolution for Everyone David Sloan Wilson recounts that it was in fact E. O. Wilson who pointed out a group selective interpretation of data he was presenting at a conference, helping to push him early on in a rather unfashionable direction. From what I have heard Wilson always believed that the empirical data was not adequately explained by a pure inclusive fitness model, and simply waited until things shook out before pushing back with more theoretically trained colleagues who had the same skepticism.
From page 30 of Sociobiology:
Despite the reality that I’ve cautioned against taking PCA plots too literally as Truth, unvarnished and without any interpretive juice needed, papers which rely on them are almost magnetically attractive to me. They transform complex patterns of variation which you are not privy to via your gestalt psychology into a two or at most three dimensional representation which can you can grok immediately. That is why History and Geography of Genes was so engrossing. You recognize patterns which were otherwise unrecognizable. But how you interpret those patterns, that’s a wholly different matter. And how those patterns arise is also not something one can ignore.
First, let’s start with an easy case. To the left is a PCA plot with four populations. Nigerians, East Asians (Chinese + Japanese), Europeans (whites from Utah), and finally, African Americans. The x-axis is the first principal component of variation, and the y-axis the second. That means that the x-axis is the independent dimension of variation within the patterns of genetic data which explains the largest fraction of the total amount of genetic variation. The sum totality of the variation can be decomposed into an large set of independent dimensions which can be rank ordered from the largest explanatory components to the smaller ones, successively by number. In a human genetic context the first principal component invariably separates Africans from non-Africans, and the second principal component often maps onto a west-east axis from Europe to the New World. Subsequent principal components can often be useful in smoking out fine scale distinctions, or relationships which are confused by the existence of similar but different signals in admixed populations.
The interpretation of this plot is rather easy. You see that African Americans lay along a continuum between Nigerians and Europeans, skewed toward Nigerians, with some outliers toward East Asians. We know from other genetic findings that ~20% of the African American ancestral quanta is European, but, that quanta is not equally distributed across the population. ~10% of the African American population is more than 50% European in ancestry, while 90% is less than 50% European. And so you have a distribution which reflects this variation. As for the outliers, I will speculate and suggest that these are indications of Native American ancestry among some African Americans.
The story I presented above is probably plausible as an explanation of the visual because we have a wealth of historical data to corroborate the plausibility of that narrative. The fit between the results from the technique of analysis of genetic variation and what scholars have long inferred from textual sources is relatively easy. It is far more difficult to look at a PCA plot, and generate a plausible narrative that you yourself accept with a high degree of confidence with little external support. It is with that caveat in mind that I present Toward a more uniform sampling of human genetic diversity: A survey of worldwide populations by high-density genotyping:
Sometimes in a narrative you have secondary characters who you want to revisit. What do to do after the story is complete? An convenient “work-around” to this problem is to find the story rewritten from the perspective of the secondary character. In broad strokes the picture is unchanged, but in the finer grained shadings different details come into sharper relief. Though the exterior action may be unaltered, it gains different context, and the interior motive may radically alter, as the nature of subjective perspective matters so greatly in the last instance. In many ways Oren Harman’s The Price of Altruism reads to me like a narrative rewritten from the perspective of a character who was a supporting protagonist in other stories. George Price, almost a novelty act elsewhere, now becomes the primary point of view character.
I could almost say that Harman, a historian of science, has given us a novel from a “shared universe” of stories. That universe is the real world. The other stories are the lives of great scientists, and the plot consists of the working out of their ideas. In the acknowledgments Harman alludes to the wide range of works where fragments of George Price’s life filters through. I have read many of the mentioned works, The Darwin Wars, Defenders of the Truth, and Narrow Roads of Gene Land. In all of these George Price cuts a quixotic figure, mercurial, brilliant and exceedingly eccentric. His plain biography already peculiar. Price began his career as a chemist, shifted to journalism and became what we today would term a professional “skeptic,” then entered into a period of productivity as an evolutionary theorist of some major impact, and finally spent his last years attempting to live the life of a serious Christian who followed God’s commands to the best of his abilities. He died tragically, committing suicide in his early 50s in 1975, homeless, destitute, and serious ill.
Earlier this week I pointed to the controversy which has erupted around the widely reported new paper, Genetic Signatures of Exceptional Longevity in Humans. Newsweek did the most thorough early reporting, but now The New York Times has published a follow up story covering the scientific criticisms to the original paper’s methodology. There’s nothing new in The Times‘ piece as such, but it shows that concerted scientific objection to the reception or interpretation of a particular finding which is widely disseminated in the media can yield results. Too often the mainstream media ends up serving as a glorified press release service, but in this case scientists are making their voices heard, and the media narrative is adjusting to the underlying discussion in the scientific community.
I’ve been told there may be more coming out which may shed light on this controversy next week. Stay tuned…
By now you’ve probably stumbled onto Wired‘s profile of Sergey Brin, and his quest to understand and overcome Parkinson’s disease through the illumination available via genomic techniques. I want to spotlight this section:
Not everyone with Parkinson’s has an LRRK2 mutation; nor will everyone with the mutation get the disease. But it does increase the chance that Parkinson’s will emerge sometime in the carrier’s life to between 30 and 75 percent. (By comparison, the risk for an average American is about 1 percent.) Brin himself splits the difference and figures his DNA gives him about 50-50 odds.
Brin, of course, is no ordinary 36-year-old. As half of the duo that founded Google, he’s worth about $15 billion. That bounty provides additional leverage: Since learning that he carries a LRRK2 mutation, Brin has contributed some $50 million to Parkinson’s research, enough, he figures, to “really move the needle.” In light of the uptick in research into drug treatments and possible cures, Brin adjusts his overall risk again, down to “somewhere under 10 percent.” That’s still 10 times the average, but it goes a long way to counterbalancing his genetic predisposition.
Do you think Brin’s chances are really 10 percent? Is he being an objective analytical machine, or is he exhibiting the ticks of systematic bias which plague wetware? This is interesting because when it comes to big-picture extrapolations individuals who come out of the mathematical disciplines (math, computer science, physics, economics, etc.) have a much better ability to construct models and project than those who come out of biology. Biology is dominated by masters of detail. The system-builders only have small niches across the sub-domains, with the exception of evolutionary biology where the system is the raison d’etre of the field. But though biologists lack strategic vision, they are often masters of tactics when on familiar ground. I would like to believe Sergey Brin’s estimate of the probability in his case, but I do wonder if biomedical scientists working on Parkinson’s are aware of powerful constraints and substantial obstacles which would force one to be less optimistic. I would of course assume that Brin though is aware of constraints, or lack thereof, because he has talked to the relevant researchers. On the other hand, would a biomedical scientist be totally candid with Sergey Brin due to even the silver of a possibility of a research grant of magnificent scope?
An urban myth, often asserted with a wink & a nod in some circles, is that a very high proportion of children in Western countries are not raised by their biological father, and in fact are not aware that their putative biological father is not their real biological father. The numbers I see and hear vary, but 10% is a low bound. People are generally not convinced when I point out that this would mean that nearly 30% of paternal grandfathers are not paternal grandfathers. Most of my scientist acquaintances fancy up the myth by suggesting that they received this datum from research on family groups (where you have to take into account the error introduced by paternity misattribution) or organ matching for purposes of donation.
Evolutionary biologist Marlene Zuk has some informal survey data which she presents in an article in The Los Angeles Times:
Mutations are as you know a double-edged sword. On the one hand mutations are the stuff of evolution; neutral changes on the molecular or phenotypic level are the result of from mutations, as are changes which enhance fitness and so are driven to fixation by positive selection. On the other hand mutations also tend to cause problems. In fact, mutations which are deleterious far outnumber those which are positive. It is much easier to break complex systems which are near a fitness optimum than it is to improve upon them through random chance. In fact a Fisherian geometric analogy of the affect of genes on fitness implies that once a genetic configuration nears an optimum mutations of larger effect have a tendency to decrease fitness. Sometimes environments and selection pressures change radically, and large effect mutations may become needful. But despite their short term necessity these mutations still cause major problems because they disrupt many phenotypes due to pleiotropy.
But much of the playing out of evolutionary dynamics is not so dramatic. Instead of very costly mutations for good or ill, most mutations may be of only minimal negative effect, especially if they are masked because of recessive expression patterns. That is, only when two copies of the mutation are present does all hell break loose. And yet even mutations which exhibit recessive expression tend to generate some drag on the fitness of heterozygotes. And if you sum small values together you can obtain a larger value. This gentle rain of small negative effect mutations can be balanced by natural selection, which weeds does not smile upon less fit individuals who have a higher mutational load. Presumably those with “good genes,” fewer deleterious mutations, will have more offspring than those with “bad genes.” Because mutations accrue from one generation to the next, and, there is sampling variance of deleterious alleles, a certain set of offspring will always be gifted with fewer deleterious mutations than their siblings. This is a genetics of chance. And so the mutation-selection balance is maintained over time, the latter rising to the fore if the former comes to greater prominence.
The above has been a set of logic inferences from premises. Evolution is about the logic of life’s process, but as a natural science its beauty is that it is testable through empirical means. A short report in Science explores mutational load and fitness, and connects it with the ever popular topic of sexual selection, Additive Genetic Breeding Values Correlate with the Load of Partially Deleterious Mutations:
Check out the #bg2010 hash-tag on twitter. There’s a lot of interesting tidbits. Here are some tweets from the presentation on the Neandertal genome in relation to the Denisova hominin (a.k.a. “X-woman”):
lukejostins SP: The Denisova finger is from the Neanderthal line, but didn’t interbreed with humans, hence looking like an outgroup
dgmacarthur: SP claims that Neanderthals and Denisova archaics are more closely related than either are to humans; intriguing.
dgmacarthur: SP: next steps: generate 10-20X coverage of Neanderthal, sequence other archaic humans (e.g. Denisova).