Evolutionary Anthropology 16:164–171 (2007)

CROTCHETS & QUIDDITIES

‘‘So Mortal and So Strange a Pang’’: A Tribute to Paul T. Baker

Is the high life a matter of adaptability or adaptation?

KENNETH M. WEISS AND ABIGAIL W. BIGHAM

An important aspect of human biol- ogy is our ability to acclimatize to essentially every environment on earth: our adaptability. A second as- pect is evolutionary, how we got the ability to do that: our adaptation. Both adaptability and adaptation have a genetic component, in the first case concerning the genetic mechanisms that enable people to respond to different environmental conditions and, in the latter, the evo- lution of those mechanisms. The two seem to be related, but are the genes the same, and how can we tell? One model system for understand- ing both adaptability and adaptation in the present as well as the evolution- ary past may be life in the hypoxic (low-oxygen) environment of high altitude, because if you live up high, you can’t escape the stresses posed by the lower partial pressure of oxygen. Beginning in the early 1960s, one of the homes of high-altitude research was the Department of Anthropology Figure 1. Paul T. Baker, founder of a breathless legacy. at Penn State, where Paul Baker (Fig. 1), his colleagues, and their students traveled the high road of human- tions at annual meetings of the Ameri- cially in molecular biology and adaptability research for many can Association of Physical Anthro- genetics, have shifted the focus from 1–3 years. In the 1980s, Paul’s col- pology. Other prominent research phenomenology to mechanism and leagues, students, and grandstudents groups have also been working on this made it possible to be much more made 10% or more of all presenta- problem, of course, but now, after a genetically specific about both adapt- considerable hiatus, there is renewed ability and adaptation. But the new research in this area here at Penn approaches also force us to confront Ken Weiss is Evan Pugh Professor, and State. Consequently, we thought it the challenge of understanding the Abby Bigham is a senior graduate stu- would not be too parochial to discuss difference between them. dent, in the Department of Anthropology recent scientific advances in the con- at Penn State University. text of honoring the Baker legacy. Paul’s academic descendants con- ‘‘THE AYRE...SO SUBTILE AND tinue to conjure understanding out DELICATE’’ VC 2007 Wiley-Liss, Inc. of thin air, but since his time the DOI 10.1002/evan.20140 Published online in Wiley InterScience research atmosphere has changed. People may have first wandered to (www.interscience.wiley.com). Major advances in technology, espe- high altitude in the Andes, Hima- CROTCHETS & QUIDDITIES Strange Pang 165

stan) who wished to secure an escort for the return trip through Hindu Cush. This escort was not granted because of the area’s rough terrain. The author goes on to say that ‘‘on passing the Great Headache Mountain, the Little Headache Mountain, the Red Land and the Fever Slope, men’s bodies become feverish, they lose colour, and are attacked with headache and vom- iting.’’8 This description of mountain sickness is more accurate than Acos- ta’s. It also indicates that the Chinese were circumspect about traveling through the Himalayas for fear of alti- tude sickness. Interest by European scientists in high-altitude physiology began in the latter half of the nineteenth century. The early work conducted in highland Mexico and Andean Peru posited the rather racist idea that people at high altitude were inferior to their coun- terparts at lower elevations. After his expedition to the Andes, the promi- nent Cambridge physiologist John 5 Figure 2. Adapting and adapted. Cover of Joseph de Acosta’s book, courtesy of the Barcroft opined that, ‘‘all dwellers at University of South Carolina special collections library. high altitude are persons of impaired physical and mental powers.’’ Consid- layas, and the Semien Moutains of problem. But it’s probably false. ering the huffing and puffing the Ethiopia, in search of game or plant Based on the altitude where Acosta advanced Europeans had to do to keep up with the barbarians, this food. How high they climbed, and residedatthetime,aswellashis seems at least a bit presumptuous. how fast, before they settled there is symptoms, it is likely that he was A Peruvian school of high-altitude unknown, but for the two high-alti- suffering mainly from gastroenteri- biology was partly a response to early tude regions we will focus on, per- tis.7 But perhaps because his whole European observations of indigenous manent habitation in the Andean entourage was suffering, de Acosta high-altitude groups and focused on altiplano dates back about 10,000 had a good insight. However, its adaptability. The father of Peruvian years, and in Tibet perhaps 25,000.4 less-than-critical repetition over sev- high-altitude biology, Carlos Monge One of the early Jesuit mission- eral centuries shows the willingness Medrano, was a physician and physi- aries who traveled to the Peruvian of science to accept, too readily, ologist, author of a classic book on Andes was Joseph de Acosta. He was ideas that we are predisposed to the subject, La Enfermedad de los the first European known to describe, accept. Andes,9 and best known for his work in 1590, what has become known as on chronic mountain sickness, which Acosta’s syndrome, soroche, or moun- can affect native and immigrant alike. 6 ‘‘ON PASSING THE GREAT tain sickness (Fig. 2). What he called His scientific interest was largely clin- ‘‘so mortal and so strange a pang’’ is HEADACHE MOUNTAIN’’ ical, but he laid the foundation for the result of suddenly moving to the The first comparable writing re- later adaptability studies by other Pe- hypoxic environment at high altitude. garding the Himalayas comes from ruvian researchers, including his son, He correctly intuited that people the Chinese classic Ch’ien Han Shu, Carlos Monge Casinelli, and Alberto require ‘‘a more gross and temperate which documents the history of the Hurtado. Over the years, Peruvian sci- ayre.’’ He noted that the populations Han Chinese from 206 B.C.E. to 25 entists examined many aspects of dis- native to the Andes don’t suffer those C.E. This encyclopedic work was ease, as well as normal growth and de- symptoms and that in others the started by Ban Biao (3–54 C.E.), then velopment in peoples at high altitude, symptoms usually go away after a few finished by his son Ban Gu (32–92 though by no means could all of these days. C.E.) and daughter Ban Zhao (35– diseases be attributed to high altitude Acosta’s writing forms the sym- 100 C.E.). In Book 96 of the series, per se. bolic cornerstone for European sci- Ban Gu describes an envoy to China Early work in the United States on ence’s historical interest in this from Ke-pin (present-day Afghani- high altitude focused on identifying 166 Weiss and Bigham CROTCHETS & QUIDDITIES

cal performance ability, and effi- ciency. Baker’s students and others have done extensive work among Tibetans as well.10 Comparative results show that although both pop- ulations have higher lung capacities than do corresponding lowlanders, they live at high altitude in physio- logically different ways. No one of these traits, by itself, seems to predominate in the high-altitude response in either population. Although understanding adaptation was the desired goal, this work has perforce mainly been phenomenologi- cal. It shows adaptability to low oxy- gen levels, but reports vary among investigators and traits as to whether there has been adaptation. In some reports, lowland migrants to high alti- tude never reach the same physiologi- cal states as those of the natives no matter how long they live at high alti- tude.10 In the Andes, people with Andean ancestry have larger birth- weight babies and less intrauterine growth restriction than do Euro- peans, which could lead to greater infant survival.11 But in other reports, Europeans and lowland Native Amer- icans seem to acclimatize fully to high Andean altitude after long periods of 2,3 Figure 3. Up there, then and now. A: The Baker site in Nunoa,~ at 2,500 M. B. A Nunoan~ exposure. Some reports say the Quechuan weathers the storm. C. The peak of Illamini over the valley of La Paz D. Boliv- same about Han Chinese relative to ian Aymara on the road to Sorata. Sources: A,B: Baker archives; C, D: photos by Abby their Tibetan highlanders.12–14 Bigham. Baker, as well as others working with the Chilean Aymara,15 was inter- the adaptive significance of the mor- ruvian research conducted by Monge ested in genetics, but the available phological and physiological differ- and Hurtado. One of Baker’s main tools provided no way to distinguish ences observed in long-term resi- concerns was that Peruvian research between variation associated with dents of the altiplano, such as the had been based on the assumption adaptability and selective adaptation. Quechua of Peru and the Aymara of that the physiological differences Genetic data at the time were basi- Bolivia, as compared to lowland pop- observed among high-altitude popu- cally confined to a small number of ulations. Much of this work was lations were the result of acclimati- protein variants, like blood groups, sponsored as part of the Interna- zation, not adaptation. Baker and his mostly with no plausible relevance to tional Biological Programme (IBP; contemporaries therefore started out high-altitude physiology, usually with 1964–1974), a research consortium with the ‘‘modern synthesis’’ as the only two alleles (genetic variant that addressed a variety of biological foundation; that is, the idea that ad- states) that could be detected. Such problems and was analogous to the aptation, not just adaptability, was data could show general levels of International Geophysical Year in involved. genetic variability and patterns of 1957–1958. Paul Baker was a leader Over many years they collected population similarity, such as that the of the Human Adaptability compo- data on a large number of physical highlanders were not genetically iden- nent of the IBP, which he and his and metabolic processes involving tical to South American lowlanders. students undertook by a large-scale, many different biological pathways However, isolation and genetic drift long-term study of the Nunoan~ Que- (Fig. 4). These included anthropo- (chance change in variant frequency chuans in Peru (Fig. 3A,B).1,2,3 metric measures, assessments of from one generation to the next in As Baker pointed out in the intro- growth and development, gestational small populations) could readily duction to Man in the Andes,2 the outcomes, and measures of oxygen account for that. Nunoa~ project was directed at over- use and ventilation capacity, blood There was no credible way to relate coming the shortfalls of the early Pe- oxygen and hemoglobin levels, physi- the observed patterns of variation to CROTCHETS & QUIDDITIES Strange Pang 167

itable component of variation are unsatisfyingly indirect. They don’t identify any particular genes, which leaves room for doubt as to their meaning. And after many thousands of years in Tibet, why is there enough remaining variation at the putative gene for selection to be detectable in a simple family study? While it’s nice to confirm that genes play a role, these results only inch a small way toward understanding. The question remains: What are the genes?

MODERN GENETICS: ARE THE QUESTIONS OR THEIR ANSWERS SEPARABLE? Thanks to recent improvements in molecular genetics, research is poised to begin identifying specific genes that are involved in high-alti- tude adaptability as well as adapta- tion. Today’s genetic studies are also greatly strengthened by advances made by physiologists with respect to oxygen-sensing systems. Genetic pathways involved in oxygen biology, such as the hypoxia inducible factor (HIF) system, have been extensively Figure 4. Life up there. Diagram from Baker’s study of the Nunoan~ Quechua illustrating characterized in recent decades (Fig. the complex influences on high-altitude life, including genetic, biological, and cultural 5). This is an ancient system by factors to be sorted out.2 which cells respond to low oxygen pressure. It clearly was not evolved natural selection. Moreover, matters out the relative environmental or de- for high-altitude life per se, but is im- were made more problematic by the velopmental contribution to a particu- portant, for example, during embryo- need to take into account the poten- lar altitude phenotype from the genesis. Cells in growing tissue tial effects of Westernization, coca genetic contribution. In a series of respond by HIF activation if they are use, and differences in way of life, studies of Aymara from Camacani, too far from the nearest capillary to physical condition, and nutrition, all Peru, genetic variation was shown to receive enough oxygen; this activa- of which can affect health and physi- have a significant but moderate affect tion stimulates vascular growth. HIF ology and, in turn, impact selection. on several anthropomorphic traits.16 is also active in gametes and gesta- In addition, possible sources of selec- A family-based study in Tibet found tion, and certainly is a plausible tar- tive pressure other than hypoxia exist; statistical evidence that an unidenti- get for fertility and embryogenesis- environmental pressures imposed by fied gene controls about 21% of varia- related selection. However, this sys- life on the altiplano include cold, tion in blood oxygen saturation, tem was already in place, so it is not increased solar radiation, and poor which affects Darwinian fitness clear what further selective pressure soil, which could lead to malnutri- through fertility and infant survival.10 was needed. One possibility is that tion. Knowing that these stresses exist However, there was no evidence there is selection for regulatory is, however, the easy part. Under- of a genetic component to this in aspects of the system. We are now standing how so many variables Andeans.17 Measures of ventilation able to revisit earlier questions posed might affect selection or, indeed, our varied considerably between these by researchers seeking to detect ability to detect the evidence of selec- populations,18 but hemoglobin con- genetic evidence of both adaptability tion, is a sobering challenge. centration had significant genetic var- and adaptation in the various physio- A direct approach to understanding iation in both.19 As we’ll see, such var- logical systems that have been stud- whether genes are involved is to esti- iability within and between groups ied. For example, each gene in a mate the heritability of variation in has a ready evolutionary explanation. pathway like HIF is a potential can- altitude-related traits; that is, to parse But studies that characterize the her- didate for variation that is involved 168 Weiss and Bigham CROTCHETS & QUIDDITIES

iation that would lead to ‘‘candidate’’ genes. Similarly, if the phenotypic differences observed between low- and high-altitude populations are only the result of adaptability, we would expect the variation present in our candidate genes to be similar in closely related low-altitude control populations to the variation observed in high-altitude populations. The approach that Mark Shriver and one of us (AB), along with col- laborators elsewhere, are taking to identifying the effects of selection is to compare existing genomic varia- tion in Andeans and Tibetans to that in closely related low-altitude popu- lations. What makes this even possi- ble is microarray technology, panels of known polymorphic sites at hun- dreds of thousands of markers that can easily and affordably be geno- typed in every individual in a study Figure 5. The HIF pathway regulates many of a cell’s physiological responses to high-alti- sample. The markers themselves are tude habitation. The different components, from the pores in the cell membrane to gene unlikely to be involved in adaptation; regulation in the nucleus, are shown. Each factor is coded by a separate gene for which they are just previously identified protein or regulatory sequence might vary. Diagram courtesy of http://www.biocarta. variable sites of known genomic com/. location. However, the pattern of dif- ferent levels of variation between in selective adaptation as well as ulation, are presumably adapted in highlanders and lowlanders may adaptability to hypoxia. all sorts of ways.20 indicate which markers’ genome Genes involved in adaptability can Mapping identifies genes specifi- regions have been affected by selec- be identified in a direct way known as cally involved in oxygen physiology, tion for adaptive variants, thus gene mapping. Basically, with poly- showing that variation in these genes reducing genetic variation in those morphic markers spaced at close affects variation in response. But this regions. For example, one of several intervals across the entire genome, contemporary variation of genetics different available tests searches the specific markers having variation that of adaptability does not imply that genome for reduced variation in is associated with variation in a the same genes have been affected short regions, evaluated by a statisti- measured response variable such as by selection in the past. To identify cal measure called lnRH. This statis- oxygen metabolism can be found. those genes, a different approach tic measures the relative variability The genes in the implicated chromo- is possible. It involves use of the in that region between Andeans and somal regions are then identified by same kinds of genome-wide genetic their lowland counterparts, an exam- looking at the human genome markers. ple of which is shown in Figure 6. sequence and can be tested for their Natural selection leaves distinct The genome regions with signifi- functional basis and for variation that signatures in the genome.21,22 In pos- cantly lower variability potentially affects the measured trait. Similarly, itive adaptive selection, if a specific reflect the effects of a history of genes known from physiological stud- genetic variant is helpful for life at selection. ies to be involved in oxygen exchange high altitude and if it leads to greater Lowlanders are only one sort of or metabolism can be sequenced in Darwinian fitness (net reproductive control or contrast sample that we individuals with different hypoxia success), then that variant will can use. We can also let the high- responses to see if their coding or reg- increase in frequency. Over time, the landers’ own genomes stand as con- ulatory variation is associated with gene will have less variation in the trols. This is because areas near those responses. A recent mapping population than it once did or less genes that have been under adaptive paper on a small sample of Sherpas variation than that in regions of the selection in their ancestors can be found very preliminary evidence of genome in which variation is not less variable than other areas in their candidate chromosomal regions, related to adaptation. If the selection same genomes. We can thus use the though if did not identify specific were recent or intense enough, we same panels of genetic markers to genes in those regions or genes that would expect, when evaluating the look along the genome of highlanders could be attributed to adaptation to amount of variation along the ge- for areas that vary significantly less hypoxia. Sherpas, like any other pop- nome, to find regions of reduced var- than others do. CROTCHETS & QUIDDITIES Strange Pang 169

ther complication is, of course, that the genome is adapting to all sorts of factors all the time, so that a signa- ture of selection does not necessarily reflect high-altitude stress. Only fol- low-up studies such as those we’ve mentioned can sort out the chance chaff from the selective grain. If the same gene shows direct evi- dence of adaptability and if its pat- tern of variation shows a signature of adaptive selection, then it will be time to get excited. So far, one of us (AB) has assessed the patterns of variation present in Andean popula- tions compared to low-altitude con- trol populations. The genomic statis- tical results are pointing to some Figure 6. Taking it to the genome. A ‘‘sliding window’’ approach in which a window the interesting HIF pathway genes, but size of 200,000 nucleotides moves along each chromosome, 50,000 nucleotides at a time, have not yet been substantiated by in each window assessing levels of variability in Andeans compared to a sample of low- 23 genotype-phenotype correlations. land Mesoamericans based on the lnRH measure. The figure shows the first 5 million But how do we interpret genes hav- nucleotides from the end of chromosome 2. The highly negative lnRH values (below the 0-line) indicate decreased variability in the Andeans compared to the Mesoamericans. ing variation that we can show affects the trait today, but don’t show signa- tures of natural selection, or vice Based on the results of this initial considerations and moving to spe- versa? This is likely to happen for search for genomic signatures of cific genotype-phenotype associa- many reasons. For example, the rele- selection, the identified candidate tions, has not yet been used to detect vant variation in phenotypes today genes will be subjected to sequenc- genetic signatures of adaptive selec- may not be variation that was related ing-based tests of selection. In this tion to high altitude, but that work is to past selection. Another possibility approach, we look for variation that in progress. is that, the distribution of selection is reduced specifically in functionally An additional challenge is pre- over many systems may make the important parts within the candidate sented by genetic drift, the changes in effects on individual components very genes. This relative reduction in vari- genetic variation that are due to the weak. When many genes affect a ation provides indirect statistical evi- chance aspects of survival and repro- trait, even under selection, chance dence of selection. More direct geno- duction. The same patterns used to may determine which ones respond type-phenotype studies can then be distinguish adaptability from adapta- most to the selection. This raises performed to show whether different tion can be the result of geographic another important question. variant states are associated with dif- isolation followed by drift, a fairly Do the Tibetan and Andean popula- ferences in a measure of physiologi- reasonable demographic scenario tions exhibit similarities or differen- cal response. given the remoteness of the Andean ces in genes or functionally different If all these tests are passed, a final altiplano and Himalayan plateau. changes in the same genes involved test can help affirm the findings. In However, genetic drift is a genome- in high-altitude adaptation? We know this test, lowland-highland admixed wide affect. If there is no adaptive that the characteristic ‘‘barrel- individuals are studied to see selection, all regions of the genome in chested’’ thorax of the Andeans can whether those with high-altitude like a population will be equally affected provide additional lung capacity in a phenotypes have inherited the puta- by it, while natural selection only way not found in Tibet. Generally, we tive adaptive genetic variants from affects specific adaptive genes. But expect to find multipathway pheno- their altiplano ancestors. Genotype- these are statistical arguments, and types like HIF or adaptive phenotypic phenotype association testing is nec- there are complications. similarities that are controlled by dif- essary to determine whether genes When we search a large ‘‘space’’ ferent genes or different suites of that appear to have been subject to like the entire human genome, we genes in these two highland groups. genetic adaptation are functionally expect to find local regions that by That would jibe with the variable relevant. This testing also will sub- chance resemble the signature of results for different measures men- stantiate the link relating the selection. Alternatively, selection may tioned earlier. There clearly are sev- observed physiological differences have occurred in other regions but eral other physiological and even between low and high-altitude be essentially undetectable: When morphological systems, such as lung groups with their respective geno- selection is a weak effect, it changes capacity, that relate to oxygen biology types. This battery of sequential test- variation only slightly more than (not to mention cold adaptation). ing, starting with purely genomic drift alone does. An important fur- Each involves many genes. 170 Weiss and Bigham CROTCHETS & QUIDDITIES

We have clear precedents indicat- A founding leader of the IBP was not tested in the high-altitude part of ing what we should expect to find in C. H. Waddington, who was inter- the IBP. But he might be pleased to high-altitude adaptation. Multiple ested in the ‘‘epigenetic landscape’’ see the opportunities that now exist genetic pathways affect two well- that relates organisms to their envi- to probe some of the more subtle studied human adaptive traits. Many ronments. Waddington believed that aspects of evolutionary ecology that pathways are involved in skin pig- processes other than simple natural the wandering of a few peasants into mentation. Recent study has shown selection could account for biological high altitude has presented. Investi- that Europeans and East Asians use diversity. One of them was ‘‘genetic gators here and elsewhere are cur- separate genetic pathways to pro- assimilation,’’ an extension of ideas rently generating the genetic data duce their light-skinned pheno- from the late nineteenth century.28 that may enable us to reconstruct types.24 Similar phenotypic conver- This and related phenomena are those wanderings. gence, but also genotypic divergence called polyphenism,29 or niche con- Many questions remain to be has been observed in adaptation to struction.30 Genetically identical answered about the way humans malaria.25–27 Because evolution organisms can express different phe- adapt to or have been adapted for works through phenotypes rather notypes in different environments. life on high. Our history at high alti- than directly on genotypes, inde- There is nothing in their genome tude may also illuminate the role of pendent or convergent evolution is that insists that they have a given culture, as well as the roles of mech- expected and well-documented. This phenotype. But if the phenotype they anisms other than classical Darwin- is what is found between Tibet and manifest in a given environment hap- ian selection, in our ability to func- the Andes in terms of phenotypes, at pens to be beneficial to their survival tion in that environment. Work in least. It will be surprising if it is not or reproduction, Darwinian selection this field today is a tribute to its pio- the genetic result as well. can favor new mutations that arise neering anthropological ancestry, in that environment and raise the largely the inspiration (if you’ll for- probability of the favorable pheno- give the pun) of Paul Baker at high WHEN ‘‘THE ORGANISM type being expressed. Over time, altitude. He, his students, and many OVERCOMES THE ‘CLIMATIC what was initially an adaptability other contemporaries laid the basis AGRESSION’ OF THE response becomes an adaptive char- from which we can aspire to use new acteristic. approaches to understand what hap- ELEVATION’’9 Humans are the ultimate choosing pens to people when they move up in The usual notion of natural selec- organism, and may offer good exam- the world. tion is that people are passively ples of an active rather than passive The same logic and approaches can screened by the environment to response to environments. Given that be taken in many other contexts in determine the outcome of the repro- hypoxia is always present at high which we try to work out how we cur- ductive sweepstakes. Cold and hy- altitude, but is escapable by paths up rently respond to the world we find poxia could do that to humans and down mountain, human adapta- ourselves in and how we got that trapped at high altitude, but that tion to this stressor may provide an way, and perhaps even where we may may not be what happened. In fact, excellent example of organismal be going in the future. Not all of it is hypoxia could illustrate an important selection. However, it is a challenge genetically predetermined, but it is alternative that could apply espe- to know how to differentiate among genetically enabled. It is valuable and cially to a species like us. We adapt natural selection, organismal selec- interesting to understand how. behaviorally and culturally in many tion, and assimilation. All may con- However, we can always use new active rather than passive ways. An tinually be at work, and life on high kinds of contrasts and comparisons. obvious example is that if people today is probably a mix of these One of the more important strategies decided whether or not to live at paths of ascent. But it will take crea- in science is to compare related spe- high altitude, those with genetically tive thinking to show this genetically. cies living in the same environment. based abilities to deal more easily One way might be that genes related The other organisms who live on with hypoxia could have been more to effects we can consciously per- high with humans have a variety of likely to go to or settle at high alti- ceive, like shortness of breath, might their own adaptations, too.31–34 Alpa- tude. There, they would have met reflect organismal selection, while cas, llamas, and guinea pigs are good and mated with others of their kind. those related to effects we can’t see, examples in the Andes. Of course the The relevant genotypes will be pref- perhaps such as immune compro- best comparison would be with other erentially found at high altitude com- mise or gestational stress on birth closely related primates. For that, we pared to lowland. This is organismal weight, might reflect classical selec- may have to turn to the Himalayas, selection, an active rather than pas- tion. Which kind of force should and we’ll need the help of Cynthia sive means of sorting genetic varia- impose more stringent selection? Beall, a Baker student who has long tion that can generate gene-specific As things turned out, Waddington worked in highland Tibet. If, like patterns in the altiplano that resem- had been some what dragged into Slavomir Rawicz’s band of escapees ble Darwinian selection. However, no his IBP role, and had little to do with from a Siberian labor camp,35 she differential reproduction would have it in practice. As far as we know, his should cross a rise and happen upon been involved. ideas of genetic assimilation were a band of Yeti’s... CROTCHETS & QUIDDITIES Strange Pang 171

NOTES 12 Garruto RM, Chin CT, Weitz CA, Liu JC, Liu TS, Altshuler D, Lander ES. 2006. Positive natu- RL, He X. 2003. Hematological differences dur- ral selection in the human lineage. Science We welcome comments on this ing growth among Tibetans and Han Chinese 312:1614–1620. column: [email protected]. There is born and raised at high altitude in Qinghai, 23 Storz JF, Payseur BA, Nachman MW. 2004. China. Am J Phys Anthropol 122:171–183. Genome scans of DNA variability in humans a feedback and supplemental mate- 13 Garruto RM, Little MA, Weitz CA. 2004. reveal evidence for selective sweeps outside of rial page at http://www.anthro.psu. Environmental stress and adaptational res- Africa. Mol Biol Evol 21:1800–1811. edu/weiss_lab/index.html. We thank ponses: consequences for human health out- 24 McEvoy B, Beleza S, Shriver MD. 2006. The comes. Coll Antropol 28:509–540. genetic architecture of normal variation in Anne Buchanan, Ralph Garruto, 14 Weitz CA, Garruto RM, Chin CT, Liu JC. human pigmentation: an evolutionary perspec- Cynthia Beall, Brooke Thomas, and 2004. Morphological growth and thorax dimen- tive and model. Hum Mol Genet 15:R176–R181. sions among Tibetan compared to Han children, John Fleagle for assistance with this 25 Weatherall DJ. 2001. Phenotype-genotype adolescents and young adults born and raised at relationships in monogenic disease: lessons from manuscript. high altitude. Ann Hum Biol 31:292–310. the thalassaemias. Nat Rev Genet 2:245–255. 15 Schull WJ, Rothhammer F, editors. 1990. 26 Flint J, Harding RM, Boyce AJ, Clegg JB. The Aymara: strategies in human adaptation to REFERENCES 1998. The population genetics of the haemoglo- a rigorous environment. Dordrecht, Holland: binopathies. Baillieres Clin Haematol 11:1–51. 1 Baker PT. 1969. Human adaptation to high Kluwer Academic. altitude. 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Books Received

 Bobe´, R., Alemseged, Z., and Dordrecht: Springer. ISBN 978-  Pickering, T. R., Schick, K., and Behrensmeyer, A. K. (2007). 1-4020-5844-8. $129.00 (cloth). Toth, N. (2007). Breathing Life Hominin Environments in the  Schutkowski, H. (2006). Human into Fossils: Taphonomic Studies East African Pliocene: An As- Ecology: Biocultural Adaptations in Honor of C. K. (Bob) Brain. sessment of the Faunal Evi- in Human Communities. xiii + xvii+296pp.Gosport:StoneAge dence. xx + 354 pp. Dordrecht: 303 pp. Berlin: Springer. ISBN 3- Institute Press. ISBN 978-0- Springer. ISBN 978-1-4020- 540-26085-4. $149.00 (cloth). 9792-2761-5. $74.95 (cloth). 3097-0. $129.00 (cloth).  Spencer, J. (2007). Anthropology,  Stringer,C.(2006).Homo  Bailey, S. E. and Hublin, J.-J. Politics, and the State: Democracy Britannicus: The Incredible (2007). Dental Perspectives on and Violence in South Asia. xiii + Story of Human Life in Brit- Human Evolution: State of the 203 pp. Cambridge: Cambridge ain. 319 pp. London: Allen Art Research in Dental Paleo- University Press. ISBN 978-0-521- Lane. ISBN 0-713-99765-8. anthropology. xxviii + 409 pp. 77746-9. $29.99 (paper). $50.00 (cloth).