Thursday, April 16, 2015

Not yet, on sustainability, it seems....

This post is triggered by the beginning of the biking season here.  Joy of joys!!  When the snow's gone and the temperature gets far enough above freezing for weaklings like me to venture out on my bike, I like to see what's changed along the many various paths that are here, since the previous autumn when I put my bike in the basement to wait out the long, icy winter.  My usual reaction is that an important message hasn't gotten through at all.

We live in a land-grant university town.  Penn State is in fact a very good university.  We have an ag school and they have some active conservation and sustainability groups.  But overall it is a money-first institution.  Each year as I venture out I see more former agricultural land being urbanized:  soil and the prior year's farmland is being paved over to make room for condos or suburban-style McMansions, or shrink-wrap or fast-food franchise outlets, or banks.  Oh, and more bars, of course.

A few years ago our President and trustees sold many, as I recall hundreds, of acres right near the edge of campus, upon which hundreds of condos are being built.  That land had been used by the ag school and its students.  Bye bye, or perhaps one would better say $ye $ye to that old-fashioned notion!

View of Circleville Farm, 2005; Penn State Daily Collegian

Circleville Farm now: US Framing
Even here it seems that the message hasn't gotten through that what's important here should be beyond the interests of the short-term 'developers' (that is, the realtors and destruction companies) and that there should instead be at least a modicum of consideration not just for the long-term future but also the quality of life.  Thousands more people come in, and what we get is more demand on water, more light, noise, and air pollution, more crime, more sewage and electricity demand, more litter.  And, of course, more business for the local banks, shrink-wrap, fast-food, and alcohol merchants.  Every new development seems to be named for what the developers destroyed to build it -- "Pheasant Glen", "Acacia Woods", "Pine Hollow".

Urban sprawl envy
It is difficult for me to grasp why, even here, the need for restrained growth and long-term sustainability, especially in regard to agriculture, is basically not felt at all.  I think that's the appropriate word for it.  Humans are humans, and we're a short-term thinking species.  We're very good at long-term awareness, but it's in the abstract.  What we feel is of the here-and-now, and in our society this means quantity more than quality of life.  Or, to be fair, quantity of life is seen as quality of life.  Until the threat looms palpably on the horizon, we will carry on with what we know and are used to.

Even here, even in a university town with an ag school, intellectual awareness of issues has little 'bite'.  It is depressing.  Even as we see stories in the news of droughts and soil loss and climate change issues, we do essentially nothing.  Without a wolf right at the door blowing hard, complacency yields to or generates deniers and other arguers-of-convenience, who reflect the general human pattern of short-term thinking.  We daily hear arguments about how to insure 'growth' in business and the economy.  Population growth is hardly on the agenda at all, either locally or globally.  Here the operative word is growth, and it's a mainstay of international development efforts as well as economics professors.  There was just an episode of the  BBC Radio4 program The Inquiry, that dealt with this problem--and asked if we've just all got tired of hearing about climate change. The same goes for population growth, and resources exhaustion.

I can ride my bike all over town, which is a very good thing.  But at night it's hard to see the stars. We may think our consumerist world is expanding, but light pollution keeps us from realizing how finite we really are.

If State College with a major university, that even has sustainability programs, can't do it, who can or will?  Maybe in the western US, where drought stares one in the face?  We shouldn't denigrate climate deniers if we act in a comparable manner.  It seems that there is only one word in our language:  "More!"  Instead, Nancy Reagan had it right: when it comes to 'development' what we need to learn is how to "Just say No!".

But if deniers want to keep their big vehicles and whatever else makes them feel righteous, climate change advocates have their own hypocrisies.  They and their publicity advocates overstate the various aspects of the science itself.  Sustainability advocates use efficient LED light bulbs and recycle their milk bottles, but they still live in big air conditioned houses and drive to work and to the store to get those milk bottles.  Climate scientists and relevant policy-makers in large numbers gambol around the world attending meetings (flying, nice hotels with fancy meals, ....) where they debate how people should cut back on greenhouse gases, rather than the boring alternative of using Skype or Google Hangout for their conferences.  This is do-as-I-say-not-as-I-do behavior and no matter how correct the climate and sustainability arguments are--and they seem essentially urgent--the threat is just not looming enough.

I, too, am a hypocrite and probably, no certainly, don't do enough to truly recognize the problem. Neither do I have any idea how, or even if, it would be possible for a people, even an educated people, to become enough aware of long-term issues to do something really major about it. I like my car (and driving to the store to get my bottles of milk)!  But I also know that as long as everyone carries on as usual, each year there will be more bike paths for me to ride, because they put them in and around all the new condo complexes, and that's great!  So, I think I'll close now, and head out....

Tuesday, April 14, 2015

Have gorillas really inbred themselves into the future?

By Anne Buchanan and Ken Weiss

NOTE:  This is a revision of our original post, because a mistake on our part was pointed out by a commenter, to whom we offer thanks.  Our main point hasn't changed....unless there are still misperceptions on our part.

BBC Earth headline: "Inbreeding Makes Mountain Gorillas Genetically Healthy." We are so tempted to add an exclamation point to that, but we won't.  Anyway, you know it's there, whether we add it or not. Everyone 'knows' that inbreeding is bad; what a juicy story!

And, to summarize, the story is this: Mountain gorillas are an endangered species, surviving now in just two small groups in central Africa, a total population of only about 800 individuals.  Their numbers had fallen to just under 300 in the 1980's, for multiple reasons including poaching and loss of habitat, but Diane Fossey made their conservation her life's work, and the population more than doubled since its lowest point.

                  Location of eastern and western gorillas; Xue et al., Science 2015

But, their small numbers led to extensive inbreeding, which is always worrisome to conservationists because it may reduce a population's ability to adapt to changing environments.  But, the BBC writes:
Now scientists have discovered inbreeding has actually benefitted mountain gorillas by removing many harmful genetic variations. They are also genetically adapted to living in small populations.
Fewer harmful genetic mutations, which stop genes functioning and can cause serious health conditions, were found in the mountain gorilla population than in the western gorilla populations.
Ok, let's step over to the actual paper ("Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding," Xue et al.), in Science last week, to get the story without the go-between.  So, the investigators sequenced the whole genomes of 13 eastern gorillas, including seven mountain gorillas and six eastern lowland gorillas.  They compared these sequences with published sequences of lowland gorillas further west, and found lower genetic diversity in both the mountain and lowland gorillas from the east, which they report as consistent with the smaller population sizes there.  Their analysis, they report, confirms that the eastern lowland and mountain gorillas are two genetically distinct populations.  Genome wide linkage disequilibrium was higher in the eastern gorillas than the western, evidence of different demographic histories of these populations, and suggesting a recent population bottleneck in the eastern gorillas.

Foraging gorilla, Congo; Wikipedia, Pierre Fidenci

In eastern gorillas, chromosomes were found to be homozygous across 34 to 38% of their length, while in western lowland gorillas, they were 13% homozygous, indicating that the eastern gorillas have a recent history of several generations of close inbreeding.  Xue et al. also report that the eastern and western populations diverged perhaps 150,000 years ago, with no mating history in the last 20,000 years or so.  And, overall, it seems that gorilla population sizes have been small for thousands of years, and thus probably have been inbreeding for all of that time.

Again comparing mountain with lowland gorillas, Xue et al found no evidence for natural selection or adaptation favoring functional genes in either group.
Such adaptation might be expected from the fact that mountain gorillas range over high altitudes (1500 to 4000 m), with consequences for diet, morphology, and physiology. However, we found no significant enrichment in any functional category of genes, although there are interesting examples related to nervous system morphology, immunoglobulin quantity, and red blood cell morphology. Mountain gorillas carry a significant excess of variants in genes associated with blood coagulation in humans (fig. S21), perhaps linked to high-altitude living. We also identified variants associated with cardiomyopathy, including in one deceased individual (Kaboko) in whom post mortem analysis revealed evidence of muscular hypertrophy. Cardiovascular disease has been identified as a notable cause of death in captive western lowland gorillas.
With respect to unfavorable effects of inbreeding, the authors report the opposite, saying that inbreeding seems to have purged deleterious mutations from the genome.  They suggest that gorillas have found workarounds for inbreeding effects, as well, such as by "natal dispersal and gene flow between isolated populations."

Xue told the BBC that gorillas have been coping with small populations for thousands of years, and,
"While comparable levels of inbreeding contributed to the extinction of our relatives, the Neanderthals, mountain gorillas may be more resilient. There is no reason why they should not flourish for thousands of years to come."
No reason? 
But, we can think of a number of reasons.  The Ebola virus has been devastating to chimps and gorillas, wiping out 95% of some groups of gorillas in which it has spread.  And, there's always the possibility that other infectious diseases may emerge, or reach these animals, and be equally, or even more devastating.

And, poaching continues to be a problem, and hunting for bushmeat.  Loss of habitat continues to be a problem.  Climate change will surely have consequences for these animals.  As with any other animal, including humans, environmental change and its consequences are unpredictable.  Whether or not any species has the genetic wherewithal to adapt to that change is unpredictable; it's impossible to know what any single gene will do in every possible environment, never mind what every gene, and every genetic interaction will do.  This is, of course, true with respect to predicting our own futures from our genomes as well. 

What is 'inbreeding' and what does it mean?
There are several things about this paper aside from the apparent obliviousness of the research report to the real threat to gorilla 'fitness', namely that they're widely projected to become extinct because of human incursion and predation, in addition to disease. We might also ask, if the western gorillas have so little relative homozygosity, why they aren't plagued with the sorts of defects that the easterners have already purged, and on the verge of collapse -- or long gone?  

The answer is that both populations (not just the eastern) did well enough to be here today.  Both low and high homozygosity are obviously good enough, because neither wiped out either population structure in their past.  So why tell the story as if one way's better? It seems to be the tired old evolutionary trope that we cannot seem to escape: To be different from is to be better than, to evolve away from is because it's a better way.  But, mutation is always happening, genetic drift is always happening, and if a variant works, it works. It isn't necessarily selected because it's better, or more adaptive, than anything that came before. 

This paper is in a sense an exaggeration of, and in a way confusion about inbreeding and its effects.  There are several meanings of 'inbreeding' that are relevant here** . The classical meaning refers to mating with close relatives relative to random-mating. The issue there is the classical one of increased incidence of recessive disorders with inbreeding.  In that context, the probability of an allele being homozygous more than just by chance: if the latter is p^2 when there is random mating, the former is p^2 + Fp(1-p), where p is the frequency of the variant in question, and F is the excess probability of being homozygous due to non-random mating. That may be because of socially constructed preferential kin-mating or just a deviation from random mating. In many, if not historically most, human populations, mating was prescribed as to be between cousins of various types. If variants are harmful but recessive so that their harm is only seen in homozygotes (both copies in a person being defective), then mating between close relatives can increase the frequency of such events, and the loss of the harmful variant from the population, but of course only at the expense of the carriers of those harmful genotypes. One can argue that if something like close-relative mating were so dangerous it would never have evolved to be, in a sense, the ancestral human way as it has.  Or, one can note that the reason for local group endogamy or exogamy (how mates are chosen in any population, human or otherwise) has to do with social structure, resource distribution, and control of internecine and intergroup strife--not because of disease genes.

The authors appear not to have done this kind of calculation, however, and samples would have been too small for it to make sense.  Instead, they looked along the genome to see what fraction was homozygous (that is, variant sites along the region in the sequenced animals).  This reflects a different use of the term 'inbreeding', and we think what this paper is referring to, is the rise in homozygosity due to genetic drift in small populations.   In a small population, rarer alleles (genetic variants) are lost more rapidly from the population, mainly just by chance. Homozygosity at a given site is an inevitable reflector of population size, and in a small population the region of a chromosome that is homozygous (not varying) would be larger than in a large outbred population. That is not an automatic indicator of a history of loss of harmful mutations, recessive or otherwise. In any population harmful variants have a shorter staying time than helpful ones, but their duration depends on many different factors that can't be inferred from the stretches of homozygosity alone.

Do western lowland gorillas, with their lack of a history of 'inbreeding' as presented by this story, show some detectable load of sub-par individuals? If so, that would be relevant news. In fact, both groups have coefficients higher than human cousins relative to each other, as a commentary on this paper notes. But so what?  In fact, and perhaps to the contrary, being too inbred in the small-population sense could, as far as just-so stories go, mean there would not be enough variation in the population to respond to environmental challenges.

What the study does no doubt actually show is that the two gorilla populations have had different demographic histories. That is ecologically interesting and perhaps useful for understanding wildlife conservation issues.  But in itself it says basically nothing about purging harmful variation except that it would be somewhat faster, on average, in one group than the other -- but only slightly so, because if that were not the case the burden of loss could have threatened the very survival of the group in the past so that it never made it to the present, which obviously isn't the case.  'Inbreeding' in headlines may have a juicy sound and catch the lascivious eye, and that's why the news media go for it so readily.

It should also be noted that extensive, detailed, biomedically documented studies in human isolate populations have found each to have particular instances of elevated recessive diseases or other traits due to inbreeding effects, but the overall burden of genetic disease has not been particularly increased, if at all.

***The often and perhaps still confusing issue of inbreeding have been clarified long ago, e.g., by Albert Jacquard in 1975, in J. Theoretical Biology, "Inbreeding: one word, several meanings", by various wrtiting of Warren Ewens back in the 70s, or see Templeton and Read, Conservation Genetics, 1994; they are discussed in any good population genetics text.

Monday, April 13, 2015

Yanomami blood sample return: Some update information

On March 25 we posted a discussion of research ethics that was brought about by the return of some blood samples we had for many years housed in our lab at Penn State.  We explained why this had been contentious, and why many aspects of the demand for return were based on reasons wholly unrelated to anything done by the investigators with these samples.  Rather, the concern had more to do with experiences of the Yanomami tribal members over many years, due to outside interference with their lives.

There was a flurry of publicity from various news sources, showing the return of the samples (links below), and we would like to correct some of what was said.  In many of the stories, the source of the samples was mis-attributed to the University of Pennsylvania, when in fact it was Penn State.  There also seems to be a misapprehension or allegations in the news stories that the samples were collected without permission and implying that we were the ones who collected them.  Whatever one's views about how the Yanomami were treated and their experience of the outside world, or how they currently feel about the samples, these involve quite irresponsible mistakes.  My lab has housed a set of these samples for many years, after the person (JV Neel) whose group collected them had retired, he divided the samples up for safekeeping and curation into three sets, one for the Anthropology department at Penn State, one for an investigator now at Penn, and one for the National Cancer Institute, where they had various potential research interests in them, in case new methods became available that could enable things to be learned about cancer that the original methods, of the '60s and '70s, were incapable of resolving.  Michigan would have destroyed them otherwise.

There is plenty of room for debate about scientific studies by the industrialized nations, of indigenous or dependent populations.  The nature of informed consent was discussed in our earlier post on this problem.  Feelings expressed now by Yanomami representatives may be entirely sincere and even justified from their point of view.  At the time, the filming of the collections and the trade goods and whatever else was involved offered in exchange as part of the Yanomami's participation, including the provision of the blood (and other biomedically related samples and information) made the collection seem totally voluntary.  The degree to which cultural and/or power differences and the like led to misunderstanding about the samples and what was to be done with them is impossible for us to know, and there are differences of views for many reasons.

Not the least of the problems is the passage of decades of time, and of the lives of both investigators and subjects.  Retrospective judgments about informed consent, coercion, recompense, and relevance of the anthropological studies to the Yanomami experience with the outside world, are important issues, but not ones we ourselves can judge.

It should also be pointed out that the issues about the Amazonian indigenes and the outside world are not new.  Indeed, around 1800, when Alexander von Humboldt visited the Yanomami general area (and one of the main sites of the work now in question), there were already long-established mission stations with a lot of western culture already brought into the area.  So external influence, helping, and/or meddling with the lives of the indigenous populations have a deep ancestry.  Hopefully, newer ethics or protections will prevent further problems of this kind.

A few of the stories (in English, Spanish and Portuguese):

- BBC:
- American Indian and Friends (BBC):
- News 24 (AFP):
- 9 News, Austrália (AFP):

Tuesday, April 7, 2015

IF: Impact Factor....or inflation factor?

As in many departments, our graduate students and post-docs here in the Penn State Anthropology Department hold weekly 'journal clubs' where recent interesting papers are discussed. Last week, the students discussed the nature, value and importance of tabulations of journal impact factors (IF), basically the citation rate per published paper. There have been many papers and commentaries on this subject in recent years, but this session focused on a paper by Brembs, Button and Munafo entitled "Deep impact: unintended consequences of journal rank," published in 2013 in Frontiers in Neuroscience.

The IF scandal
This article assesses the assigned IF of journals relative to their retraction, error or fraud, and reliability or replicability rates. The objective picture of the IFs is not encouraging. Statistical analysis shows that the 'major' journals--the expensive, exclusive, snobbish high-status ones are, in terms of the quality and accuracy of their content no better, and arguably worse than the less prestigious journals. We won't go into the details but basically there is a rush to publish dramatic results in those status journals, the journals are in business to attract and generate attention, and that leads them to receive, and publish, splashier claims. In this self-reinforcing pattern they garner the honors, so it is worrisome that they appear to do this without actually publishing the best research or, worse, systematically publishing unreliable work.

It is of course not wrong to publish in such journals, nor is all they publish of questionable merit. If you can get good papers in those journals, of course, do it! The point for us here is that faculty, and young faculty in particular, are judged by granting agencies, department heads and deans to a substantial extent by the IFs of the publications on their CVs. It is bad enough for the competition of over-populated academe to be based on the mythology of unending exponential growth, but it's worse if the system is such that it can be effectively gamed or used to reinforce those at the top so they can stay at the top, often without their work being substantially better than that of their peers. This squeezes those not at the top down into the lower-status strata of the disciplines -- and when it comes to jobs, if they can't manage high IFs or high numbers of publications, it may well mean they are out of work!

Our student seminar discussed this problem and the effect it may have on their careers, if their work is going to be judged by a somewhat rigged, and inaccurate, scoring system. If they can't get into the high-IF elite publishing club, which is somewhat self-reinforcing, how can they compete for jobs and grants and get their work known?

We have several reactions to this. For students and others who may have a stake in (if not in the heart of!) the system, here are a few thoughts on alternatives to the high IF journals. The picture is grim, but in some surprising ways, not at all hopeless.

Some thoughts for students:
First, TheWinnower, founded by Josh Nicholson, a graduate student at Virginia Tech, is a new online site where one can send papers but also where blogs and other such new-media communications can be published, and these publications given a DOI (formal document identifier) and hence be more regularly citable and permanently archived. It's but one of many new communication venues. A lot of what is on these media is of course superficial fluff, but (Sssh!! don't tell anyone!) so is a lot of any sort of publication, even (believe it or not!) in the 'major' journals and so has it always been, even in the old-time printed journals of yore.

Secondly, there are allies in any movement towards change, not just from the grass roots where pressure for social change usually arises. There are thoughtful and progressive administrators, and serious scholars and scientists, who are resisting the pressure to use IF score-counting, in career evaluations, purportedly to make them more 'objective'.

And, there are many people making their way largely and in various ways on blogs, open-access publishing, online teaching, communicating with people via Twitter and other outlets (most of which we, being quite senior, probably don't even know of!). Writing for public media of all sorts has always been a mainline, legitimate way to build careers in anthropology, especially its sociocultural sides. But generally, critiques of the system at all levels, such as repeated revelations about score-counting bureaucracies and IF biases, as well as objections to closed access publishing, will have their impact if they are repeated often and loudly enough.

Thirdly, ironically and reassuringly perhaps, the tightening of the grant prospects and the well-documented concentration of funding in the hands of senior investigators, means more people will have to rely less on grants, and their university employers will simply have to recognize that. Teaching and other forms of service, scholarship, and outreach will simply have to be reinvigorated. Universities aren't just going to close shop because their grant funds shrink. They're not even going to be able to keep shifting towards hiring poorly paid Instructors. So the field is open for innovation and creativity.

Fourthly, also ironically, the greater the rush to the Big Journals, the better it may be for the job prospects of current grad schools? Why? Well, fewer people in the running for each job will have such publications on their CVs than perhaps was the case in the past. As long as applicants realize that others will want the same jobs they do, and they develop their skills and depth of thought accordingly, they'll compete well. After all, colleges and universities will simply not be able to hold out for those few with BigName publications, even if they wanted to. They'll be 'stuck' having to evaluate people on their actual merits. And, not so trivial as you might think, most of their faculty haven't got BigName papers either, and might not want to be outshone by adding a junior hyper-achiever to their midst. Indeed, many less research-intensive but wholly academically serious places feel, correctly, that applicants for faculty positions who have BigName publications don't really want to work there and will move on as soon as they can get a ‘better’ job, and/or in the meantime won't be dedicated to teaching, students and the local institution. So things aren't always as dire or as one-sided as they seem--even if times are relatively difficult right now.

Fifth, if the intense rigors of the research-intensive Fast Lane appeal to you, well, you know the gig and its competitive nature, and if you get your advanced degree from a fine and well-regarded program that will give you a chance at getting the brass ring. Those avenues are of course open, even if highly competitive.

"Painted Pony Bean" by Liveon001 © Travis K. Witt - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons -

But why does anyone even tally such things as impact factors?
An obvious question one should be why anybody would tally impact factors in the first place? Who has what to gain? The answer has to be that it is in someone's interest and someone will gain by it. After all, when some of us started our careers, there was no such thing (or, the earlier version Science Citation Index, was remote, in the library, laborious to look through and then usually only for legitimate resource searching). Scholarship itself was on average at least as good as now, careers were made without bean-counting but more on merit and substance, and bean-counting expectations were lower (and respect for teaching higher), the grant game much, much less intense.

IF scores are computed by a commercial company, Thompson-Reuters, as---what? As a favor to the publishing industry, and for what we would call a kind of academic bourgeois market for baubles and vanity. Journals self-promote by gaming their IFs, universities self-promote by gaming their faculty's IF ratings. They have money to make by promoting and, yes, manipulating their IFs (see the above article for just some of the ways). One can ask whether there is even a single reason for such score-keeping to be done other than for reasons of artificially constructed status hierarchies.

One motivation for this bean-counting is the heavy proliferation of online journals. Some of these are very highly respected, and deservedly, while others are chaff or, worse, scams for making money playing on fears and insecurities of faculty members needing advancement. IFs will at least be some assistance to an administrator or grant reviewer who wants to have an idea of a faculty candidate's record. But if the IFs are systematically unreliable, or manipulated, or even reverse indicators of actual work quality as some articles like the one above have suggested, that is a rather lame rationale for using IFs. Administrators evaluating their faculty members' careers should look at the actual work, not just some computer-tallied score about it. That may not be easy, but administrators are well-paid and accepted their jobs, after all.

There was in the past an insider Old Boy network in academe, that discriminated more arbitrarily in terms of funding, over-powerful Editors who controlled who published and what they published, and less opportunity for women and cultural minorities (based on ethnic as well as university status hierarchies). To increase fairness, but also to avoid discrimination lawsuits, and to play the self-promotion PR spin game, universities and their administrative officials learned the value of being 'objective' and hiding behind Excel spreadsheets rather than judgment. More objectivity did in many ways dislodge the older elite insider networks, but a system of elites has clearly re-established itself, and manipulable IF factors and their associated commercial incentives have helped reestablish some dominance in the academic system. It may still be wide open in many ways, but is heavily burdened by the game because the corporate university has become so money-oriented. This is very well documented. Things like IFs serve those interests.

The academic world will experience change, and is changing, and the new ways of communication are better and faster and more open-structured than ever. They make life more frenetic, but that will probably calm down because it's exhausting everyone. There will of course always be an elite, and for some that's a happy community to be part of. But it's not to everyone's taste. How long it will take coup-counting administrators to accept these other venues such as online communications, is unclear, but it's happening.

Social change requires resistance to the status quo, usually organized resistance (or else money-based leverage). Bureaucracies do need to be pressured, by faculty, graduate students and post-docs, and people like Department Heads and Chairs. But, it has to happen, and it will.

Wednesday, April 1, 2015

Redpolls: genetically similar, phenotypically different

Redpolls are a group of small birds in the finch family, members of the genus Acanthis.  They breed in the far north, but sometimes migrate as far south as the central US in winter, when food is scarce further north.  They rely on a small variety of seeds, and sometimes travel a remarkable thousands of miles to find them.

Range of the Common Redpoll; Source: Cornell Lab of Ornithology

All redpolls share characteristic red markings on their heads, but otherwise these birds vary enough that they've been thought to comprise as many as six separate species, based on plumage and morphology.  Most commonly, ornithologists have treated them as three species; the Common Redpoll, the Hoary (or Arctic), and the Lesser.  Now a new paper ("Differentially expressed genes match bill morphology and plumage despite largely undifferentiated genomes in a Holarctic songbird," Mason and Taylor) reports a DNA sequencing study that suggests that the redpolls are in fact a single species.

Common Redpoll; Wikipedia Commons

Arctic Redpoll; Wikipedia Commons; (13667519855)" by Ron Knight from Seaford, East Sussex, United Kingdom -  Licensed under CC BY 2.0 via Wikimedia Commons
Lesser Redpoll by Lawrie Phipps derivative work: MPF (talk) - Carduelis_cabaret.jpg. Licensed under CC BY 2.0 via Wikimedia Commons
A figure from the Mason and Taylor paper makes the differences more apparent:

From Figure 1, Mason and Taylor, 2015

As Gustave Axelson recently wrote in his post about this study for the Cornell Lab of Ornithology All About Birds blog, seeing a Hoary redpoll can be one of those Moby Dick-like quests for a birder intent on adding it to his or her lifelist.  But Mason and Taylor report, after sampling 77 redpolls of very different phenotype, and sequencing 20,000 SNPs in the genome, and 215,000 in the transcriptome (that is, mRNA transcribed from different genes), with gene expression data and ecological niche modeling, they find very little variation between the different redpolls. In contrast, as Axelson points out, genetic comparisons between other similar species of birds, such as black-capped and Carolina chickadees, has found substantial variation all across the genome.

Mason and Taylor write, "we present evidence of (i) largely undifferentiated genomes among currently recognized species; (ii) substantial niche overlap across the North American Acanthis range; and (iii) a strong relationship between polygenic patterns of gene expression and continuous phenotypic variation within a sample of redpolls from North America."

As evolutionary biologists, Mason and Taylor are interested in the processes that lead to phenotypic diversity and speciation. "The Holarctic redpoll finches (Genus: Acanthis) provide an intriguing example of a recent, phenotypically diverse lineage; traditional sequencing and genotyping methods have failed to detect any genetic differences between currently recognized species, despite marked variation in plumage and morphology within the genus."

Mason and Taylor write that interspecific breeding has been observed, as have birds with characteristics of two different species, though phenotypic variation has been observed to be continuous throughout the redpoll range.  But no one has been able to document significant variation in either nuclear or mitochrondrial DNA.  So, if they are genetically so similar, how is it that these birds look different enough to be considered separate species?  The authors propose three possible scenarios:
The paucity of genetic differentiation within the redpoll complex, despite marked phenotypic variation across a Holarctic distribution, could be the result of multiple evolutionary scenarios (Marthinsen et al. 2008): redpolls may be comprised of (i) a single, undifferentiated gene pool that exhibits phenotypic polymorphism, in which phenotypic differences reflect locally adapted demes or neutral phenotypic variation within a single metapopulation; (ii) multiple gene pools that have recently diverged, in which incomplete lineage sorting has hindered the capacity of previous studies to differentiate populations or species; or (iii) multiple divergent gene pools that are actively exchanging genes through hybridization and introgression via secondary contact.
They compared the niches of hoary and common redpolls and determined that hoary redpolls prefer higher latitudes while common redpolls show less of a preference and are more widespread, with much overlap.  But they don't believe that the difference was enough to explain morphological differences between the birds.  That is, geographic isolation, the usual explanation for speciation, doesn't explain the phenotypic variation observed among redpolls.

Mason and Taylor note that the lack of outlier SNPs suggests that the different redpoll species, as now recognized, share a very recent ancestry.  If there were outliers, this would suggest that the birds had had a long history of no contact, during which time genetic variants arose and spread, but then the species reunited, and the interbreeding would have dispersed much, but not all, of those variants between the entire family.  That is, option i above; this is a single undifferentiated gene pool that exhibits phenotypic polymorphism.
Intriguingly, we found novel differences in gene expression that are correlated with redpoll phenotypes, suggesting that gene expression might play an important role in generating phenotypic diversity among redpolls.
This is intriguing.  Mason and Taylor suggest that redpolls should now be considered a single species,  although as Axelson says, this is up to the American Ornithologists Union.  But, given the very low genetic diversity even between widely dispersed birds, and the fact that phenotypic variation is continuous within the genus, it makes sense.  They further suggest that gene expression differences could be due to environmental conditions which trigger phenotypic plasticity in traits like bill width or plumage coloration.

Without whole genome sequencing, these results remain suggestive.  There may be as of yet unknown regions of the genome that are responsible for the variation seen in this species, but the lack of variation in SNPs throughout the genome suggest this is probably not going so.

Evolutionary considerations and the species problem
Evolutionary biologists know that there is a 'species problem'.  That is, only individuals are clear-cut distinct natural units (and, given their colonization by bacteria and the like, even they aren't all that discrete).  Species would be next, but it is about group properties and there are many definitions.  The most commonly accepted is that a species is a group of individuals that can successfully mate and produce fertile offspring.  Similar individuals whose offspring are always sterile would be assigned different species.  Different appearance need not imply mating incompatibility (as, for example, people from Africa and Polynesia, who are inter-fertile).

Single genetic changes have been found to lead to mating incompatibility, as between populations of fruit flies.  Of course changes of any sort can do this in the case of individual human couples.  If there is mating incompatibility among groups, at least, we call them different species.  Among other reasons, the expectation is that over time they will diverge in their genes and traits, with or without the aid of natural selection, and become ever more different.  Only with shared mating would these differences be blended and circulated through a species' population.

We can note four important points here.  First, species can be defined in many ways, but the idea of genetic isolation as an enabler of separate adaptation and divergence, that goes back to Darwin, is important in accounting for the evolution of diversity.  Second, speciation is a separate phenomenon from diversity of traits.  The latter is found both within and between populations of the same species. These are obvious but subtle points, often missed or overlooked even by biologists who equate natural selection and trait differences with species differences.  Mating incompatibility enables the accumulation of trait differences, but trait differences do not in themselves enable speciation.

Thirdly, what we haven't mentioned yet, is polyphenism.  This is a well-known phenomenon in which the same genotype can yield very different phenotypes (traits) in different environments.  This can happen if something in the diet produces pigments, or it can happen if genes are expressed, or not, depending on environmental conditions, leading to environment-specific results, in different individuals with the same genotype or the same genotype in different environments.  For example, the brown goldfinches in our back yard are turning yellow as spring comes.

Fourth, individual groups whose members could physically and genetically mate successfully, but don't, either because they are isolated from each other, don't come into contact, or just simply don't do it even if they could, are sometimes considered to be different species.  Usage varies and it's a judgment call, with  no external 'law' necessitating the definition.

There is no one principle or rule about by which biological species can be defined by trait comparisons, or genomic comparisons alone.  Each case is different, and since genotypic differences  or trait differences can, but needn't indicate, species differences, one has to study each case on its own merits.  That's not always easy, but it's the nature of life.

Monday, March 30, 2015

Antibiotic resistance

Ken and I just saw Michael Grazione's excellent, sobering film, Resistance, about the looming loss of antibiotics in the medicinal arsenal.  Bacteria that can make us very ill, and even kill us, are quickly, and unavoidably developing resistance to the chemicals that control them.  As Meryn McKenna writes in her excellent, also sobering piece, "Imaging the Post-Antibiotic Era", a world without antibiotics is going to look a lot like 1935; simple infections will become fatal once again, routine surgery, and cancer treatments that require repressing the immune system, and so on will no longer be possible. (McKenna is a journalist specializing in public health issues; her work is always worth reading, and she has a major role in the film.)

There are several very serious problems here, as we stare into the maw of the post-antibiotic era: despite the fact that the problem is widespread and growing, antibiotics are still being widely, and wantonly misused.  And, economic and political interests are standing in the way of changing this.

Penicillin, of course, was the first antibiotic discovered, in the 1930's.  Even before it was being widely used, bacteria were developing resistance.  Indeed, all antibiotics quickly lose their effectiveness, as the discoverer of penicillin, Alexander Fleming, warned in the 1940's, because they are a potent artificial selective force for resistance.  That's why they should be used only when necessary.

Year of first use and then clinical resistance for each antibiotic; Nature Chemical Biology, 2007; Clatworthy et al.

Antibiotics are like any other environmental agent when it comes to the evolutionary dynamics of any species, including bacteria.  If gene variants are present in the bacterial population that allow a subset of bugs to survive the chemical onslaught, this leads to resistance.  Antibiotics and chemotherapy against tumor cells are similar in this regard -- generally not strong enough to wipe out the entire population of cells.  When protective mutations are present, the overall population diminishes initially, as the majority of susceptible individuals are killed off, which leaves the field to the resistant few, which then proliferates, rendering therapy that was previously beneficial to the patient useless.

The situation is usually not quick or simple, but this is the simple nature of evolutionary adaptation.  Molecular attacks on cells can in principle act as selective factors that lead to resistance to the attack. There is no perfect or permanent solution, unless there is a mode of attack so fundamental to the target cells that they simply cannot evade it by modifying their own molecular makeup.  Such modes would be very desirable, but are not generally part of the arsenal we have against microbes or cancer cells and the like.

Instead, intervention approaches need to be used cleverly and sparingly so that resistance mutations don't have any advantage in the organism's population.  Indeed, since these organisms like bacteria (or your normal body cells) are the produce of eons of adaptation, most changes will be at least slightly harmful if they do anything, and will be outcompeted into oblivion by the 'normal' competitors in the population.  The problem is that this basic evolutionary truth is too often neglected. The reasons are only human, about short-sightedness, unawareness, personal vested interests, and so on.

There are several ways in which antibiotics are over-used that apparently lead to the present state of the problem.  Doctors and patients both are part of the problem; patients demanding treatment, even for viral infections, and doctors prescribing antibiotics just in case the infection is actually bacterial.    Of course, a big villain in the piece, discussed at length in Resistance, is routine use of antibiotics in animal agriculture, to promote growth in their densely raised livestock.  These are well-documented ways in which too much use leads to natural selection of resistant strains.

As the film also notes, there are widely known financial reasons for under-development of antibiotics by pharmaceutical firms.  There are also many technical limits, such as that many pathogens have not been growable and hence testable in the lab.  Clever ways around these problems probably exist--but we must make the research fundable.

There is no current known way to avoid the development of antibiotic resistance.  But, eliminating its use as a growth promoter in livestock would slow down the speed at which new drugs become useless, culturing infected tissues in real time in the doctor's office so that only bacterial infections are treated with antibiotics would help, patients using them for the proper length of time would help, and so on.

More research into drugs that are less likely to spawn resistance would help enormously as well.  And, subsidies for drug companies who do choose to invest in what is not a highly profitable class of drugs.  We need somehow to decouple research from profits so that this research will be done.  But this requires recognition of the enormity of the problem and its potentially catastrophic consequences.  If we take that seriously, we would divert huge amounts of funds in this research direction.

Infectious diseases and their potential future pandemic effects are far more important to study than many of the things we are currently pouring money into.  Of course, we think that much of research on enumerating individually trivial genetic variants related to late-onset, mainly environmentally caused diseases (the goal of the proposed 'precision' medicine) is hugely wasteful.

Indeed, many who do genomic research that leads hardly anywhere have the gear and technical skills to take the antibiotic issues on with much more potential for real health gains.  There's no sense in knowing a person's minor genetic risks factors for, say, adult-onset diabetes, if they're going to be eaten alive by bacteria first.  That's research emperors fiddling while Rome burns.

Thursday, March 26, 2015

The 'obstetric dilemma' hypothesis unraveled

Right now I'm giving this talk at the annual meetings of the American Association of Physical Anthropologists. Here's the link to Session 15. Costly and Cute: How Helpless Newborns Made Us Human, where you'll see the participants, their talk titles and abstracts. This symposium evolved out of a seminar at the School for Advanced Research back in the summer of 2014 when I was very pregnant and on the cusp of facing my own obstetric dilemma.

Let’s see how far we can unravel this epic hypothesis in 15 minutes or less. To start, here are the two most important seeds I hope to plant today in hopes that you’ll read up on these things further:  One. The obstetric dilemma is a hypothesis, not a fact. And… Two. The obstetric dilemma is an elegant idea, and would be an extraordinary example of human exceptionalism if true.  But it bears the burden of proof. So what is the obstetric dilemma hypothesis? In a nutshell…

We use it to explain at least these two observations, and often there are more: First, childbirth is difficult and risky. And, second, humans are born with only about 30% of our adult brain size, but for chimps it’s 40%.  Why? The “obstetric dilemma” hypothesis. Constrained by bipedalism, the human pelvis constrains gestation length and fetal brain and body growth, while making childbirth difficult and dangerous.  Which, put differently, is the hypothesis that the unique human pelvis uniquely impacts human parturition and life history. Here’s a good example of how the obstetric dilemma is often presented as a common fact, even in a book that aims to have us rethink old assumptions:

“You can’t give birth to large-brained infants and also walk on two legs trouble-free, no matter how hard you try.” Alright so, locomotion’s running the show, but does it deserve to? That is, does selection for bipedalism limit the birth canal from widening and relieving a laboring mother’s difficulty?

As of now, even taking a new dynamic approach over the old static one, like Anna Warrener and her colleagues do, there is no strong history of support for the idea that wide or women’s hips are costlier or less efficient than narrow or male’s hips. This is, at present, the best approach to the question of whether women are presently at an upper limit in pelvic dimensions that selection for bipedalism will allow. And although it does not test the obstetric dilemma directly, it demonstrates that our perspective on sexual dimorphism has been biased toward seeing female bodies as compromised compared to a male ideal. 

Relatedly, recent additions to the hominin fossil record have lifted us from the temptation to see a progressive march through time to arrive at our bipedal perfection. There are numerous reasons the hominin pelvis evolved over the last several million years, making it unlikely that our present anatomy is what is “required” for bipedalism as is so often phrased. We can only assume that the few pelvic specimens in the hominin fossil record are testament to the variable morphology that has worked both for bipedalism as well as childbirth over the last several million years. Still, if bipedalism isn’t limiting the birth canal and causing childbirth difficulty, what is? Or, asked another way, there is an explanation for why chimpanzees have it so much easier than we do. So what is it?

The answer could still be that selection for bipedalism is constraining the pelvis and it has not yet been demonstrated.  The biomechanics of pregnancy may adaptively constrain pelvic dimensions, along the lines of what Katherine Whitcome and colleagues described for the spine. Further, limitations to tissue strength and other such properties of soft tissues of the pelvic floor may constrain pelvic dimensions, especially during pregnancy or as a result of it. But it must be noted that pelvic prolapse occurs in cows and sheep, not just bipeds.   Other significant contributors to childbirth difficulty include, but are not limited to: position of the laboring woman, position of the fetus and the umbilical cord, function of the placenta, uterus and cervix, muscular and bodily weakness, slow labor progression, multiple fetuses, preeclampsia, gestational diabetes, and age at first birth, young or old. At present, our impressions of hellish human childbirth are biased to a degree by Hollywood as well as the medical industry. So we may have to place some heavy blame on culture for our having it so much harder than chimpanzees. However, the rise in c-section rates from 5% to around 30% over the last several decades is not entirely due to unnecaesareans, as there has been a concurrent secular increase in neonatal size in hospitals as well. And that recent trend may be best explained by work being done by Jonathan Wells and his colleagues…

Although the tight fit between fetus and mother’s pelvis may have occurred millions of years prior, agriculture has had a remarkable and perhaps the most dramatic effect. Agriculture’s influence on diet and overall health has affected both the development of the female pelvis and the growth of her fetus during gestation. Undernourished mothers can birth relatively large babies due to adaptive responses to protect fetal growth during pregnancy, and regardless of maternal condition, larger babies are associated with longer labors and higher incidences of medical interventions. It is highly likely that there was never more childbirth difficulty than there is now and in recent history.  Plasticity has been both a blessing and a curse. Okay, so if childbirth difficulty may be new and is due to a complex vortex of proximate and ultimate explanations, not due solely or largely to locomotor selection on birth canal size, then what about our being born with only 30% of our adult brain size? 

Could the obstetric dilemma explain our relative immaturity at birth?  Which is to say, does the human pelvis uniquely influence gestation length and fetal growth? 

Or are we born early to experience a rich period of stimulation and learning, crucial to the development of human cognitive and neuromuscular function as Portmann hypothesized? According to the extra-uterine spring hypothesis, the pelvis does not limit gestation and fetal growth, the benefits to life outside mother do. These two hypotheses for gestation length and fetal development have humans born early or underdeveloped. A third does not. 

When the energetic and metabolic costs of pregnancy and lactation are considered, gestation ends and the birth process is initiated when pregnancy reaches a critical point at which the mother can no longer support her growing fetus. Fetal energy demands (black circles) increase exponentially during gestation.  Maternal energy expenditure (grey squares) rises during the first two trimesters but reaches a metabolic ceiling in the third, as total energy requirements approach 2.0x basal metabolic rate.  Projected fetal energy requirements for growth beyond 9 months (dark, dashed line) quickly exceed the maximum sustainable metabolic rates for human mothers (horizontal, dashed line).  After parturition, infant energy demands increase more slowly, and maternal energy requirements while lactating do not exceed the maximum sustainable metabolic rates. The hormonal cascade that is involved in triggering human birth has been described by Peter Ellison’s metabolic crossover hypothesis. We suggested that although the data are far better for humans, this broad and more ultimate hypothesis that we called EGG likely applies to other species since, among placental mammals, maternal body size (a proxy for metabolism) is a good predictor of gestation length, fetal mass, and fetal brain mass as the work of Bob Martin and others work has demonstrated. Still, this doesn’t answer the question as to whether humans are born early or underdeveloped. But it doesn’t need to because folks have known for a while that ….

Human gestation is not short and seems to be even longer than expected for a primate of our body size. Relatedly, a human mother does not invest less in pregnancy than expected; she bears a large infant with a large infant brain for a primate of her body size. Humans are born with absolutely larger brains than other primates. How can we explain all this? Here’s one hypothesis:

[Text redacted to avoid spoilers. See abstract for Herman Pontzer's talk this morning here.]

One of the most common reactions to the EGG hypothesis and in defense of the obstetric dilemma is that …

… lactation is even costlier than gestation!

And this is coming, I think, from the point of view of lifetime life history theory where we assume that mammals maximize gestation length to put off lactation unless there is something adaptive about shortening gestation and sucking up those extra lactation costs. For many, this is assumed to be why we push gestation right up to pelvic limit. But then what’s adaptive about starting lactation early for all the other great apes which don’t gestate to the pelvic limit? Why not, instead, hypothesize that pregnant apes reach their EGG limit prior to their pelvic one and pregnant humans reach our EGG limit closer to our pelvic limit. In other words, our birth canal has been selected to be as adequately capacious but not as comfortable as theirs. Another common reaction to the EGG hypothesis has been…

… but the tight fit is too much of a coincidence to ignore. And I have a cheeky retort that involves my nostril and my finger, but kindly and seriously…Okay…

Well then let’s not ignore the other coincidences in other primates that clearly aren’t equipped with our bipedal pelvis. What explains their tight fits at birth? Could those explanations apply to humans? That would be the spirit of the EGG hypothesis which we have only modeled for humans so far but deserves to be tested by building the same model with other primates. Yet another common reaction I hear is…

… but why doesn’t the birth canal get bigger to make childbirth easier? And I’ve touched on this already in different ways. But another way to address this is…

It has. That we have sexual dimorphism in the bony dimensions of the birth canal and that everyone in here knows which one is male and which one is female speaks directly to the notion that the female pelvis (and not the male’s) has adapted to accommodate our relatively big babies. The adaptation works terrifically in a sort of no pain, no fitness gain kind of way. And this last common reaction I want to share is, again, all about that 30% of adult brain size at birth.

… but humans are clearly born premature!

 Well then, so are other primates and with and without a tight fit at birth, without habitual bipedalism, and without our level of encephalization. Comparing humans to altricial mammals (like carnivores, rodents, and lagomorphs) is arguably more poetic than scientific. Among anthropoids, Fragaszy and colleagues have described capuchins as relatively altricial too, given how they are only able to thermoregulate within a narrow temperature range, and have less postural control and locomotor ability just after birth compared to Old World monkeys and many platyrrhines with comparable available studies. It cannot be coincidence that neonatal capuchins have the smallest relative brain size (~50%) of all primates save for chimpanzees (~40%) and humans (~30%), meaning that they, like us, have more postnatal brain growth to accomplish compared to other primates. Now, for fun, let’s take humans out of the equation and marvel at chimpanzees instead…

Why are chimpanzees born with only 40% of their brain size when capuchins are born with 50%?! Among anthropoids, chimpanzee infants are even more helpless with their slow development and long period of dependency. For the first few months of their lives, chimpanzee infants are actively alert for only 10 percent of the day. As we’ve seen, it’s not their pelvis forcing them out early. It could be the extrauterine spring hypothesis; they’re born when they’re born to receive adaptive stimulation outside of the womb. But it could boil down to the fact that pregnant placental mammals can only grow a fetus up to a limit and then getting out there into the world is a wonderful thing for developing all there is to mammalian sociality as well. Given the trend toward greater altriciality among encephalized primates, capuchins, chimps, and humans might be better described as “less precocial” rather than singled out as somehow altricial. 

And maybe we drove ourselves to this state. Maybe we’re relatively helpless as infants because we can be, that is, because of the relaxed selection afforded by hominin caregivers. Apes are infant coddlers, and assuming our shared ancestors were too, this could have ramped up long ago, with meddling, manipulative parents and alloparents relaxing selection on infant independence, allowing them to evolve paddled feet, weak muscles, fat heavy bodies, and huge heavy heads. A scenario like this would push the origins of helicopter parenting back, potentially, into the Pliocene.

Many of our questions, even the most ultimate evolutionary ones, would be answered if we knew what triggered labor in humans and other primates. Ellison’s metabolic crossover seems to be the strongest hypothesis, but this is a research area that begs our attention. . Of course the clinical implications are significant but such knowledge would also shed light on why chimpanzees and many other primates and mammals give birth so far in advance of reaching a pelvic limit. If there is one labor trigger for all of us, how do we explain this variation in birth weight and gestation length in this large human sample? Is it metabolism and energetic throughput alone? Most probably not. It’s more likely that labor is a reaction to any number of stressors and included in that could be the size of the pelvis, but then this trigger would be a unique development in humans that would not explain the end of gestation in any species without a tight fit. Getting even more evolutionarily complex… if it all comes down to a fetal timer, then each and every species would have its specifically timed fetal timer to end gestation, and that, although not impossible, just doesn’t seem like a strong hypothesis when compared to a maternal metabolic and energetic constraint.

There is so much more to discuss, there are so many remaining questions, but I’ll end here and leave you with this: Without increasing ability to make nonhuman primate comparisons, there is little hope for knowing how bipedalism, adiposity, taillessness, encephalization, culture, etc. contribute to the evolution of pregnancy, childbirth, infancy, and how we parent and alloparent.  Live primate studies (and those of all placental mammals that pertain to these questions) are crucial if we are to explain how humans have such costly infants yet have much shorter inter-birth intervals than the rest of the hominoids. Without more detailed comparison we cannot know how costly our pregnancies and the resulting infants truly are. Primates that birth twins and practice cooperative breeding, like marmosets, hold great potential for answering many questions about reproductive physiology, metabolic limits and behavioral correlates. But for now, as far as the obstetric dilemma hypothesis goes, intense childbirth and intensive parenting are not so easily explained by bipedal pelvic anatomy. Gestation length, fetal growth, childbirth processes, and neonatal helplessness are all connected to the bipedal hominin pelvis one way or another, but whether they are fundamentally influenced by it is not an easy argument to make. The way I see it, as far as human evolutionary hypotheses go, the obstetric dilemma has gone from top dog to underdog. Support for the obstetric dilemma requires much deeper digging. And we anthropologists are great at that. Thank you.

References and relevant resources
Abitol MM. 1987. Obstetrics and posture in pelvic anatomy. J Hum Evol. 16(3): 243–255.

Abitol MM. 1993. Adjustment of the fetal head and adult pelvis in modern humans. Hum Evol. 8(3): 167-85.

Abitol MM. 1996. The shapes of the female pelvis. Contributing factors. J Reprod Med. 41(4): 242-50.

Aiello LC, Wells  JCK. 2002. Energetics and the evolution of the genus Homo.
Ann Rev Anthropol. 31: 323-38.

Arsuaga J-L, et al. 1999. A complete human pelvis from the Middle Pleistocene of Spain. Nature. 399: 255-258.

Basso O. 2014. Reproductive epidemiology in an evolutionary perspective: Why bigger may not be better. Curr Epidemiol Rep. DOI 10.1007/s40471-014-0008-2.

Berge C, Goularas D. 2010. A new reconstruction of Sts 14 pelvis (Australopithecus africanus) from computed tomography and three-dimensional modeling techniques. J Hum Evol. 58: 262–72.

Berge C, Orban-Segebarth R, P Schmid. 1984. Obstetrical interpretation of the Australopithecine pelvic cavity. J Hum Evol. 13: 573-87.

Betti L, von Cramon-Taubadel N, Manica A, Lycett SJ. 2013. Global geometric morphometric analyses of the human pelvis reveal substantial neutral population history effects, even across sexes. PLoS ONE. 8(2): e55909.

Billat ,V., Lepretre, P.M., Heugas, A.M., Laurence, H.M., Salim, D., & Koralsztein J.P. (2003). Training and Bioenergetic Characteristics in Elite Male and Female Kenyan Runners. Med Sci Sports Exerc, 35, 297–304.

Bogin, B. (2006). Modern human life history: the evolution of human childhood and fertility. In: K. Hawkes & R.R. Paine (Eds). The Evolution of Human Life History. (pp. 197-230). Oxford, England: K. James Currey Ltd.

Borries C, Gordon AD,  Koenig A. 2013. Beware of primate life history data: A plea for data standards and a repository. PLoS ONE. 8(6): e67200.

Brown EA, Ruvolo M, Sabeti PC. 2013. Many ways to die, one way to arrive: how selection acts through pregnancy. Trends in Genetics. 29(10): 585-92.

Burton GJ, et al. 2015. Human evolution: brain, birthweight and the immune system. Phil Trans R Soc B 370: 20140061

Capellini, I., Venditti, C., & Barton, R.A. (2011). Placentation and maternal investment in mammals. Am Nat, 177(1), 86-98.

Chene G, Tardieu AS, Trombert B, Amouzougan A, Lamblin G, Mellier G, Coppens Y. 2014. A species; odyssey: evolution of obstetrical mechanics from Australopithecus Lucy to nowadays. Euro J Obstetrics & Gynecology and Reprod Bio. 181: 316-20.

Cho, S.H., Park, J.M., & Kwon, O.Y. (2004). Gender differences in three dimensional gait analysis data from 98 healthy Korean adults. Clinical Biomechanics, 19, 145–152.

Cunnane SC, Crawford MA. 2003. Survival of the fattest: fat babies were the key to evolution of the large human brain. Comp Biochem and Phys Part A. 136: 17-26.

Daniels, J., Krahenbuhl, G., Foster, C., Gilbert, J., & Daniels, S. (1977). Aerobic responses of female distance runners to submaximal and maximal exercise. Ann NY Acad Sci, 301, 726–733.

Davis-Floyd R, Cheyney M. 2009. Birth and the big bad wolf: An evolutionary perspective. Childbirth Across Cultures. The History of Non-Western Science. Selin H ed. DOI 10.1007/978-90-481-2599-9_1

DeSilva J, Lesnik J. 2006. Chimpanzee neonatal brain size: Implications for brain growth in Homo erectus. J Hum Evol. 51: 207-12.

DeSilva J. 2011. A shift toward birthing relatively large infants early in human evolution. Proc Natl Acad Sci USA. 108(3): 1022-27.

Dixson A. 2009. Sexual Selection and the Origins of Human Mating Systems. Oxford, England. Oxford University Press.

Dolea C, AbouZahr C. 2003. Global burden of obstructed labor in the year 2000: Evidence and information for policy (EIP), World Health Organization, Geneva, July 2003. Global Burden of Disease. pp. 1-17.

Douglas PH. 2014. Female sociality during eht daytime birth of a wild bonobo at Luikotale, Democratic Republic of the Congo. Primates. 55: 533-42.

Dufour, D.L., & Sauther, M.L. (2002). Comparative and evolutionary dimensions of the energetics of human pregnancy and lactation. Am J Hum Biol, 14(5), 584–602.

Dunsworth HM, Warrener AG, Deacon T, Ellison P, Pontzer H. 2012. Metabolic hypothesis for human altriciality. Proc Natl Acad Sci USA. 109(38): 15212-16.

Dunsworth, H.M. (2006). Proconsul heseloni feet from Rusinga Island, Kenya. Doctoral dissertation, The Pennsylvania State University.

Eide MG, et al. 2005. Size at Birth and Gestational Age as Predictors of Adult Height and Weight. Epidemiology, 16(2),  175-181 doi: 10.1097/

Ellison P. 2001. On Fertile Ground: A Natural History of Human Reproduction. Cambridge, Mass. Harvard University Press.

Epstein, H.T. (1973).  Possible metabolic constraints on human brain weight at birth.  Am J Phys Anthropol, 39, 135-136.

Falk D, Zollikofer CPE, Moromoto N, Ponce de Leon MS. 2012. Metopic suture of Taung (Australopithecus africanus) and its implications for hominin brain evolution. PNAS.

Ferber, R., McClay Davis, I., & Williams, D.S. (2003). Gender differences in lower extremity mechanics during running. Clinical Biomechanics, 18, 350–357.

Figlio D, Guryan J, Karbownik K, Roth J. 2014. The effects of poor neonatal health on

Fragaszy DM, Visalberghi E, Fedigan LM. 2004. The Complete Capuchin: The biology of the genus Cebus. Cambridge, England. Cambridge University Press.

Frank, L.G., & Glickland, S.E. (1994). Giving birth through a penile clitoris: parturition and dystocia in the spotted hyaena (Crocuta crocuta). J Zoology, 234(4), 659-665.

Garwicz M, Christensson M, Psouni E. 2009. A unifying model for timing of walking onset in humans and other mammals. PNAS USA. 106(51): 21889-93.

Gittleman JL, Thompson SD. 1988. Energy allocation in mammalian reproduction. Am Zool 28: 863-865.

Gould SJ. 1977. Ontogeny and phylogeny. Cambridge, Mass. Harvard University Press.

Grabowski MW, Polk JD, Roseman CC. 2011. Divergent patterns of integration and reduced constraint in the human hip and the origins of bipedalism. Evolution. 65: 1336–56.

Grabowski, M.W. (2012). Hominin obstetrics and the evolution of constraints. Evol Biol 10.1007/s11692-012-9174-7.

Grand TI. 1992. Altricial and precocial mammals: A model of neural and muscular development. Zoo Biol. 11: 3-15.

Green D, Alemseged Z. 2012. Australopithecus afarensis scapular ontogeny, function, and the role of climbing in human evolution. Science. 338(6106): 514-17.

Gupta, J.K, & Nikodem, C. (2000). Case report: Maternal posture in labour. Euro J Ob & Gyn and Reprod Biol, 92, 273-277.

Hagen, D.R., Shuey, C.P., & Watkins, J.L. (1984). Restriction of uterine space reduces litter size in feral ossabaw swine. Biol Reprod, 30, 423-426.

Hamilton, B.E., Martin, J.A., Ventura, S.J. (2011). Births: preliminary data for 2010. Natl Vital Stat Rep 60(2),1-25.

Hammond KA,  Diamond J. 1997. Maximal sustained energy budgets in humans and animals. Nature. 386: 457–62.

Hamner, S.R., Seth, A., & Delp, S.L. (2010).  Muscle contributions to propulsion and support during running. J Biomech, 43, 2709–2716

Hewett, T.E. (2005). Biomechanical measures of neuromuscular control and valgus loading of the knee predict anterior cruciate ligament injury risk in female athletes: A prospective study. Am J Sports Med, 33, 492–501.

Hewett, T.E. (2006). Anterior cruciate ligament injuries in female athletes: Part 1, mechanisms and risk factors. Am J Sports Med, 34, 299–311.

Hirata S, Fuwa K, Sugama K, Kusoniki K, Takeshita H. 2011. Mechanism of birth in chimpanzees: humans are not unique among primates. Biol Lett. 7(5): 686-88.

Holloway RL, Boadfied DC, KJ Carlson. 2014. New high-resolution computed tomography data of the Taung partial cranium and endocast and their bearing on metopism and hominin brain evolution. PNAS. 111(36): 13022-27.

Hrdy S. 2009. Mothers and Others. Cambridge, Mass. Harvard University Press.

Jandó, G., Mikó-Baráth, E., Markó, K., Hollódy, K., Török, B., & Kovacs, I. (2012). Early-onset binocularity in preterm infants reveals experience-dependent visual development in humans. PNAS USA, 109(27),11049–11052.

Kasarik LB, Adolph KE, TAmis-Lemonda CS, Bornstein MH. 2010.WEIRD Walking: Cross-cultural research on motor development. Behav Brain Sci. 33(2-3): 95–96.

Kibii JM, Churchill SE, Schmid P, Carlson KJ, Reed ND, de Ruiter DJ, Berger L. 2011. A partial pelvis of Australopithecus sediba. Science. 333(6048): 1407-1411.

Konje JC, Ladipo OA. 2000. Nutrition and obstructed labor. Am J Clin Nutr. 72: 291-97.

Konner, M. (2010). How childhood has evolved. Chronicle of Higher Education, May 9.

Krogman W. 1951. The scars of human evolution. Sci Am, 185, 54–57.

Kurki HK. 2013. Skeletal variability in the pelvis and limb skeleton of humans: Does stabilizing selection limit female pelvic variation? Am J Hum Biol. 25(6): 795-802.

Kuzawa CW. 1998. Adipose tissue in human infancy and childhood: An evolutionary perspective. Yrbk Phys Anthropol. 41: 117-209.

LaVelle M. 1995. Natural selection and developmental sexual variation in the human pelvis. Am J Phys Anthropol. 98: 59-72.

LaVelle M. 1995. Natural selection and developmental sexual variation in the human pelvis. Am J Phys Anthropol. 98: 59-72.

Leutenegger W. 1982. Encephalization and obstetrics in primates with particular reference to human evolution. Armstrong E, Falk D eds. Primate Brain Evolution: Methods and concepts. Plenum: New York. pp. 85-95.

Lewton KL. 2011. Evolvability of the primate pelvic girdle. Evol Biol. 39: 126–39.

Liston WA. 2003. Rising caesarean section rates: can evolution and ecology explain some of the difficulties of modern childbirth? J R Soc Med. 96: 559-61.

Long, J.A. (2012). Dawn of the Deed. Chicago, University of Chicago Press.

Lovejoy CO, Suwa G, Spurlock L, Asfaw B,  White TD. 2009. The Pelvis and Femur of Ardipithecus ramidus: The Emergence of Upright Walking. Science. 326: 71.

Lovejoy CO. 2005. The natural history of human gait and posture: Part 1. Spine and pelvis. Gait and Posture. 21: 95-112.

Lovejoy, C.O., Heiple, K.G., & Burstein, A.H. (1973). The gait of Australopithecus. Am J Phys Anthropol, 38, 757–779.

Lynch, M. (2007). The frailty of adaptive hypotheses for the origins of organismal complexity. PNAS, 104, 8597-8604.

Martin RD. 1983. Human brain evolution in an ecological context. Fifty-Second James Arthur Lecture on the Evolution of the Human Brain. New York. American Museum of Natural History.

Martin RD. 1996. Scaling of the mammalian brain: the maternal energy hypothesis. News Physiol Sci. 11: 149-56.

Martin RD. 1998. Comparative aspects of human brain evolution: scaling, energy costs and confounding variables. The origin and diversification of language. Wattis Symposium Series in Anthropology: Memoirs of the California Academy of Sciences.  Jablonski NG, Aiello LC,  eds. No. 24. pp. 35-68

Martin, R.D. (2013). How We Do It. New York, NY: Basic Books.

Montagu, A. (1961). Neonatal and infant immaturity in man. JAMA, 178, 56.

Navarete, A., van Schaik, C.P., & Isler, K. (2011). Energetics and the evolution of human brain size. Nature, 480, 91-93

Naya, D.E., Spangenberg, L., Naya, H., & Bozinovic, F. (2013). How does evolutionary variation in basal metabolic rates arise? A statistical assessment and a mechanistic model. Evolution, 67(5), 1463-1476.

Neilson, J.P., Verkuyl,D.A., & Bannerman, C. (2005). Tape measurement of symphysis-fundal height in twin pregnancies. BJOG, 95(10), 1054-1059.

Nelson, R.C., Brooks, C.M., & Pike, N.L. (1977). Biomechanical comparison of male and female distance runners. Ann NY Acad Sci, 301, 793–807.

Neubauer, S., & Hublin, J-J. (2012). The evolution of human brain development. Evol Biol 10.1007/s11692-011-9156-1

Newman T, Lengyel C, Pavlicev M,  Muglia LJ. 2014. Human evolution, genomics and birth timing: New approaches for investigating preterm birth.
NeoReviews. 15:17.

Noakes, D.E., Parkinson, T.J., & England, G.C.W. (2001). Arthur’s Veterinary Reproduction and Obstetrics, eighth edition. Edinburgh, Scotland: Saunders.

Perez-Gomez, J., Rodriguez, G.V., Ara, I., Olmedillas, H., Chavarren, J., González-Henriquez, J.J., et al. (2007). Role of muscle mass on sprint performance: gender differences? Eur J Appl Physiol, 102, 685–694.

Peterson CC, Nagy KA,  Diamond J. 1990. Sustained metabolic scope. Proc Natl Acad Sci USA. 87: 2324–28.

Pfeiffer S, Doyle LE, Kurki HK, Harrington L, Ginter JK, CE Merritt. 2014. Discernment of mortality risk associated with childbirth in archaeologically derived forager skeletons. International J Paleopathology. 7: 15-24.

Pike I. 2005. Maternal stress and fetal responses: Evolutionary perspectives on preterm delivery. Am J Hum Biol. 17: 55-65.

Pinto-Correia, C. (1997). The ovary of Eve: Egg and sperm and preformation. Chicago, Ill.: University of Chicago Press.

Plavcan M. 2000. Inferring social behavior from sexual dimorphism in the fossil record. J Hum Evol. 39(3): 327-44.

Plunkett, J., Doniger, S., Orabona, G., Morgan, T., & Haataja, R., et al. (2011). An evolutionary genomic approach to identify genes involved in human birth timing. PLoS Genet, 7(4), e1001365.

Pontzer H, et al. This morning. Humans, the high-energy ape: hominoid energetics and life history evolution. Program of the 84th Annual Meeting of the American Association of Physical Anthropologists. March 25-28, 2015.

Pontzer H, Raichlen DA, Gordon AD, Schroepfer KK, Hare B, O’Neill MC,
Muldoon KM, Dunsworth HM, Wood BM, Isler K, Burkart J, Irwin M, Shumaker RW, Lonsdorf  EV, and SR Ross. 2014.  Primate energy expenditure and life history. Proceedings of the National Academy of Sciences USA. 111(4): 1433–1437.

Pontzer H, Raichlen DA, Shumaker RW, Ocobock C,  Wiche SA. 2010. Metabolic adaptation for low energy throughput in orangutans. Proc Natl Acad Sci USA. 107(32): 14048–52.

Portmann A. 1969. A Zoologist Looks at Humankind. Schwabe: Basel. Translated in 1990 German text by Schaefer J. New York, NY: Columbia University Press.

Powers, C.M. (2010). The influence of abnormal hip mechanics on knee injury: A biomechanical perspective. J Orthop Sports Phys Ther 10.2519/jospt.2010.3337.

Prentice AM, Goldberg GR. 2000. Energy adaptations inhuman pregnancy: limits and long-term consequences. Am J Clin Nutr. 71: 1226-32.

Ramsbottom, R., Nute, M.G., & Williams, C. (1987). Determinants of five kilometre running performance in active men and women. Brit J Sports Med, 21, 9–13.

Ridley, M. (1995). Brief Communication: Pelvic sexual dimorphism and relative neonatal brain size really are related. Am J Phys Anthropol, 97, 197-200.

Roberts AM, Thorpe SKS. 2014. Challenges to human uniqueness: bipedalism, birth and brains. J Zool. 292: 281-89.

Robson SL, van Schaik CP,  Hawkes K. 2006. The derived features of human life history.  The Evolution of Human Life History. Hawkes K, Paine RR, eds. Oxford, K. James Currey Ltd. pp. 17-44

Rosenberg K, Trevathan WR. 2002. Birth, obstetrics, and human evolution. BJOG. 109(11): 1199–1206.

Rosenberg K, Trevathan WR. 2007. An anthropological perspective on the evolutionary context of preeclampsia in humans. J Reproductive Immunology. 76: 91-97.

Rosenberg K, Trevathan WR. 2014. Evolutionary obstetrics. Evolution, Medicine, and Public Health, p. 148. DOI: 10.1093/emph/eou025

Rosenberg KR, Trevathan WR. 1995. Bipedalism and human birth: The obstetrical dilemma revisited. Evol Anthropol, 4(5), 161-168.

Rosenberg KR. 1992. The evolution of modern human childbirth. Yrbk Phys Anthropol. 35: 89-124.

Roy RP. 2003. A Darwinian view of obstructed labor. Obstetrics and Gynecology. 101(2): 397-401.

Rozzi, S.L., Lephart, S.M., Gear, W.S., & Fu, F.H. (1999). Knee joint laxity and neuromuscular characteristics of male and female soccer and basketball players. Am J Sports Med, 27, 312–319.

Ruff CB. 2010. Body size and body shape in early hominins: implications of the Gona pelvis. J Hum Evol. 58: 166-78.

Ruff, C. (1998). Evolution of the hominid hip. In E. Strasser, J. Fleagle, A. Rosenberger & HM McHenry (Eds). Primate locomotion: recent advances. New York, NY: Plenum Press.

Ruff, C.B. (1995). Biomechanics of the hip and birth in early Homo. Am J Phys Anthropol, 98, 527–574.

Rutherford JN, Tardiff SD.2008. Placental efficiency and intrauterine resource allocation strategies in the common marmoset pregnancy. Am J Phys Anthropol 137(1): 60-68

Sacher GA, Staffeldt EF. 1974. Relation of gestation time to brain weight for placental mammals: implications for the theory of vertebrate growth. Am Nat. 18(963): 593-615.

Sakai T, et al. 2012. Fetal brain development in chimpanzees versus humans. Curr Biol, 22(18), R791–R792

Sayer D, Dickinson SD. 2013. Reconsidering obstetric death and female fertility in Anglo-Saxon England. World Archaeology. DOI 10.1080/00438243.2013.799044.

Schultz A. 1949. Sex differences in the pelves of primates. Am J Phys Anthropol, 7(3), 401-424.

Scott, J.R. et al. (editors). (1994). Danforth’s Obstetrics and Gynecology, 7th edition. Philadelphia, PA.: J.B. Lippincott Co.

Shorten, A., Donsante, J., & Shorten, B. (2002). Birth position, accoucheur, and perineal outcomes: Informing women about choices for vaginal birth. Birth, 29(1), 18-27.

Simpson SW, et al.  2008. A female Homo erectus pelvis from Gona, Ethiopia. Science, 322, 1089–1092.

Smith, L.K., Lelas, J.L., & Kerrigan, D.C. (2002). Gender differences in pelvic motions and center of mass displacement during walking: stereotypes quantified. J Women Health Gend Based Med, 11, 453–458.

Tague RG, Lovejoy CO. 1986. The obstetric pelvis of A. L. 288-1 (lucyLucy). J Hum Evol. 15: 237-94.

Tague RG. 2011. Fusion of coccyx to sacrum in humans: Prevalence, correleatees, and the effect on pelvic size, with obstetrical and evolutionary implications. Am J Phys Anthropol.

Tague, R.G. (1989). Variation in pelvic size between males and females. Am J Phys Anthropol, 80, 59-71.

Tague, R.G. (1992). Sexual dimorphism in the human bony pelvis, with a consideration of the Neandertal pelvis from Kebara Cave, Israel. Am J Phys Anthropol, 88, 1–21.

Thibault, V., Guillaume, M., Berthelot, G., El Helou, N., Schaal, K., Quinquis, L., Nassif, H., Tafflet, M., Escolana, S., Hermine, O., & Toussaint, J.F. (2010). Women and men in sport performance: the gender gap has not evolved since 1983. J Sports Sci Med, 9, 214-223.

Thompson ME. 2013. Comparative reproductive energetics of human and nonhman primates. Annu Rev Anthropol. 42: 287-304.

Thorburn, G.D., Hollingworth, S.A., & Hooper, S.B. (1991). The trigger for parturition in sheep: fetal hypothalamus or placenta? J Dev Physiol, 15(2),71-9.

Trevathan W, Rosenberg K, eds. In review. Costly and Cute: How helpless babies make us human. SAR. Santa Fe.

Trevathan WR, Rosenberg K. 2000. The shoulders follow the head: postcranial constraints on human childbirth. J Hum Evol. 39: 583-86.

Trevathan, W.R. (2010).  Ancient Bodies, Modern Lives: How evolution has shaped women’s health. Oxford, England: Oxford University Press.

Trevathan, W.R., Smith, E.O., & McKenna, J.J. (2008). Evolutionary Medicine and Health.  Oxford, England: Oxford University Press.

Trinkaus E. 1984. Neanderthal pubic morphology and gestation length. Curr Anthropol. 25(4): 509-14.

Turner MJ, Rasmussen MJ, Boylan PC, MacDonald D, Stronge JM. 1990. The influence of birth weight on labor in nulliparas. Obstetrics and Gynecology. 76(2): 159-63.

Walker A. 2009. The strength of great apes and the speed of humans. Curr Anthropol. 50(2): 229-34.

Wall-Scheffler CM, Geiger K, Steudel-Number KL. 2007. Infant carrying: The role of increased locomotory costs in early tool development. Am J Phys Anthropol. 133: 841-846.

Wall-Scheffler CM. 2012.  Energetics, locomotion, and female reproduction: Implications for human evolution. Annu Rev Anthropol. 41: 71-85.

Walrath D, Glantz MM. 1996. Sexual dimorphism in the pelvic midplane and its relationship to Neandertal reproductive patterns. Am J Phys Anthropol. 100: 89-100.

Walrath D. 2003. Rethinking Pelvic Typologies and the Human Birth Mechanism. Curr Anthropol. 44: 5-31.

Warrener AG, et al.  2015. A Wider Pelvis Does Not Increase Locomotor Cost in Humans, with Implications for the Evolution of Childbirth. PLOS ONE

Washburn, S. 1960. Tools and human evolution. Sci Am. 203: 3–15.

Watts E. 1990. Evolutionary trends in primate growth and development. In DeRousseau C (ed): Primate Life History and Evolution. New York: Wiley-Liss, p. 89-104.

Weaver TD, Hublin J-J. 2009. Neandertal birth canal shape and the evolution of human childbirth. PNAS. 106(20): 8151-8156.

Weiner S, Monge J,  Mann A. 2008. Bipedalism and parturition: An evolutionary imperative for Cesarean delivery? Clin Perinatol. 35(3): 469-478.

Wells JCK, Desilva JM,  Stock JT. 2012. The obstetric dilemma: An ancient game of Russian roulette, or a variable dilemma sensitive to ecology? Yrbk Phys Anthropol.  149(55): 40-71.

Wells JCK. 2015. Between Scylla and Charybdis: renegotiating resolution of the ‘obstetric dilemma’ in response to ecological change. Phil Trans R Soc B 370: 20140067.

Weyand, P.G., Sternlight, D.B., Bellizzi, M.J., & Wright, S. (2000). Faster top running speeds are achieved with greater ground forces not more rapid leg movements. J Appl Physiol, 89, 1991–1999.

Whitcome KK, et al. 2007. Fetal load and the evolution of lumbar lordosis in bipedal hominins. Nature, 450, 1075-1078.

Wildman DE, Uddin M, Romero R, Gonzalez JM, Than NG, Murphy J, et al. 2011. Spontaneous abortion and preterm labor and delivery in nonhuman primates: Evidence from a captive colony of chimpanzees (Pan troglodytes). PLoS ONE. 6(9): e24509.

Wittman AB, Wall LL. 2007. The evolutionary origins of obstructed labor: bipedalism, encephalization, and the human obstetric dilemma. Obstet Gynecol Surv. 62: 739-48.

World Health Organization. 2005. World Health Report: Make Every Woman and Child Count. Geneva. World Health Organization

Zanolli, C., Bondioli, L., Manni, F., Rossi, P., & Macchiarelli, R. (2011). Gestation length, mode of delivery and neonatal line thickness variation. Human Biology, 83(6), 3.

Zuk M. 2013. Paleofantasy. New York: W.W. Norton.