23andMe sale Monday April 11

Details here.

RE this blog: Busy right now, but more real posts coming eventually.

What are the genomic drivers of the rapid evolution of PRDM9?

Ponting CP. What are the genomic drivers of the rapid evolution of PRDM9? Trends Genet. 2011 Mar 7. [Epub ahead of print] [abstract]

Mammalian Prdm9 has been proposed to be a key determinant of the positioning of chromosome double-strand breaks during meiosis, a contributor to speciation processes, and the most rapidly evolving gene in human, and other animal, genomes. Prdm9 genes often exhibit substantial variation in their numbers of encoded zinc fingers (ZFs), not only between closely related species but also among individuals of a species. The near-identity of these ZF sequences appears to render them very unstable in copy number. The rare sequence differences, however, cluster within ZF sites that determine the DNA-binding specificity of PRDM9, and these substitutions are frequently positively selected. Here, possible drivers of the rapid evolution of Prdm9 are discussed, including selection for efficient pairing of homologous chromosomes or for recombination of deleterious linked alleles, and selection against depletion of recombination hotspots or against disease-associated genome rearrangement.

Similarity in Recombination Rate Estimates Highly Correlates with Genetic Differentiation in Humans

Laayouni H, Montanucci L, Sikora M, Melé M, Dall'Olio GM, et al. (2011) Similarity in Recombination Rate Estimates Highly Correlates with Genetic Differentiation in Humans. PLoS ONE 6(3): e17913. doi:10.1371/journal.pone.0017913

Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans. We calculated the recombination rates between adjacent pairs of 636,933 common single-nucleotide polymorphism loci in 28 worldwide human populations and analyzed them in relation to genetic distances between populations. We found a strong and highly significant correlation between similarity in the recombination rates corrected for effective population size and genetic differentiation between populations. This correlation is observed at the genome-wide level, but also for each chromosome and when genetic distances and recombination similarities are calculated independently from different parts of the genome. Moreover, and more relevant, this relationship is robustly maintained when considering presence/absence of recombination hotspots. Simulations show that this correlation cannot be explained by biases in the inference of recombination rates caused by haplotype sharing among similar populations. This result indicates a rapid pace of evolution of recombination, within the time span of differentiation of modern humans. [. . .]

Taking into account only the common hotspots shared by all populations within a given continental region, the proportion of shared hotspots between continental regions is maximum between Europe and Middle East and North Africa (0.52), Europe and Central South Asia (0.44) and between Middle East and North Africa and Central South Asia (0.41). These values are, as expected, much lower when considering Sub-Saharan African or East Asian populations (Table 4). An interesting outcome from this analysis is the number of hotspots common to non African human populations compared to Sub-Saharan Africans. The proportion of hotspots shared between these two groups is only 17.4%, which is a small proportion given the recent out of Africa origin of non African population, and also show that the pace of evolution of hotspots is substantial. Figure S3 shows, as an example, patterns of recombination rates for SNPs where a hotspot event was detected in at least one population. Most variation is observed between continental groups while there is a substantial pattern sharing among populations belonging to the same continental group. [. . .]

Recombination rate appears to be a rapidly changing parameter, indicating that the underlying factors shaping the likelihood of a recombination event, such as DNA sequences controlling recombination rate variation, also change. The change is strongly detectable also in terms of presence or absence of recombination hotspots even if at the present stage it is not possible to measure the relative importance between changes in intermediate recombination rates and the appearing or disappearing of recombination hotspots. This is consistent with recent data showing that allelic variants of PRDM zinc fingers are significantly associated with variability in genome hotspots among humans [8]. The results obtained in this work contribute to the growing perception of recombination not as fixed feature of the genome of a species, but as a phenotype with ample genetic variation.

Elite Afr-Am sprinters more admixed than Afr-Am non-athletes?

Though hardly definitive, this study certainly lends no support to the notion that black dominance of short sprints in the US can be explained purely as a consequence of West African DNA.

The purpose of this study was to compare the mtDNA haplogroup data of elite groups of Jamaican and African-American sprinters against respective controls to assess any differences in maternal lineage. The first hypervariable region of mtDNA was haplogrouped in elite Jamaican athletes (N=107) and Jamaican controls (N=293), and elite African-American athletes (N=119) and African-American controls (N=1148). Exact tests of total population differentiation were performed on total haplogroup frequencies. The frequency of non-sub-Saharan haplogroups in Jamaican athletes and Jamaican controls was similar (1.87% and 1.71%, respectively) and lower than that of African-American athletes and African-American controls (21.01% and 8.19%, respectively). There was no significant difference in total haplogroup frequencies between Jamaican athletes and Jamaican controls (P=0.551 ± 0.005); however, there was a highly significant difference between African-American athletes and African-American controls (P<0.001). The finding of statistically similar mtDNA haplogroup distributions in Jamaican athletes and Jamaican controls suggests that elite Jamaican sprinters are derived from the same source population and there is neither population stratification nor isolation for sprint performance. The significant difference between African-American sprinters and African-American controls suggests that the maternal admixture may play a role in sprint performance.
[. . .]
Among African Americans, no individual haplogroup produced significant findings for Bonferroni-adjusted critical a of 0.003, presented in Table 3. Interestingly, the nonsub- Saharan paragroup was highly significant in overrepresentation within athletes. This may indicate an advantage possessed by more admixed individuals. While maternal admixture contributing any environmental and social advantages with regard to athletic training and development cannot be ruled out, further investigation into the amount of admixture in the autosomal genome is required to assess the overall non-African genomic component. In addition to assessing differences between athletes and controls in either group, the haplogroup distributions of Jamaican controls and African-American controls were also compared. These two populations were found to have significantly different haplogroup distributions (Po0.001), providing further mitochondrial evidence of different population histories. The matrilineal distribution of both athlete populations differs significantly, suggesting no discernable distribution of lineages indicative of elite sprinting in these genetically distinct groups of West African descent.

Reference: Deason et al. Scand J Med Sci Sports. 2011 Mar 16. doi: 10.1111/j.1600-0838.2010.01289.x. [Epub ahead of print]

Ethnic background of the British Royal family

From the website of genealogist William Addams Reitwiesner, who died last year. The Ethnic ancestry of Prince William (b. 1982):

Every so often, someone will state that the British Royal Family is "not British", that they are instead "German" or "Foreign". Since this belief seems to be somewhat wide-spread, and since the genealogy of many members of the British Royal Family is fairly well known, it seemed to me that it would be fairly easy to quantify precisely how "British" or "non-British" the British Royal Family is. This webpage shows the results of my work.

A few links

The Unsilenced Science: The Racial Controversy of a Violent Gene

Viking ancestry explored on the Isle of Man by researchers

Viking's first took up settlement on the Isle of Man at the end of the 8th century.

The research team will analyse Y chromosomes which are linked with surnames and then estimate proportions of Norwegian ancestry in these samples.

Recent adverse trends in semen quality and testis cancer incidence among Finnish men

These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors.

Genetic Genealogy and the Single Segment. One minor point of disagreement. The author writes:

What this means for genealogy on 23andMe is that for two people sharing one segment identical by descent there is no way to reliably estimate how far back the common ancestor was. Furthermore, no improvement in software can possibly change that, because the limitation is imposed by the genetics itself.

For relatively sparse databases and at present levels of testing resolution, this is more or less true. However, two things could potentially change this: (1) denser databases linked to pedigree information should allow small segments in living individuals to be attributed with high confidence to particular distant ancestors in many cases; (2) high-quality complete genome sequences should provide additional resolution, potentially allowing the level of relationship represented by a small segment to be estimated with greater precision (e.g. using STR haplotypes, recent/novel SNPs, and other sorts of variation not captured by SNP microarrays).

Open thread (6)

Links, off-topic discussion, etc. Previous open threads: 1 2 3 4 5

Craniometric data support a mosaic model of demic and cultural Neolithic diffusion to outlying regions of Europe

Full text is free:

The extent to which the transition to agriculture in Europe was the result of biological (demic) diffusion from the Near East or the adoption of farming practices by indigenous hunter–gatherers is subject to continuing debate. Thus far, archaeological study and the analysis of modern and ancient European DNA have yielded inconclusive results regarding these hypotheses. Here we test these ideas using an extensive craniometric dataset representing 30 hunter–gatherer and farming populations. Pairwise population craniometric distance was compared with temporally controlled geographical models representing evolutionary hypotheses of biological and cultural transmission. The results show that, following the physical dispersal of Near Eastern/Anatolian farmers into central Europe, two biological lineages were established with limited gene flow between them. Farming communities spread across Europe, while hunter–gatherer communities located in outlying geographical regions adopted some cultural elements from the farmers. Therefore, the transition to farming in Europe did not involve the complete replacement of indigenous hunter–gatherer populations despite significant gene flow from the Southwest Asia. This study suggests that a mosaic process of dispersal of farmers and their ideas was operating in outlying regions of Europe, thereby reconciling previously conflicting results obtained from genetic and archaeological studies.

Jean M comments:

Their results are remarkably neat, showing two clearly distinct lineages, with comparatively little inter-mixture, confirming the picture from the archaeology of the LBK, for example, which seems to indicate that farmers and foragers kept to their own zones.

This helps to explain why the presumed Neolithic Y-DNA haplogroups G, E and J do not dominate Europe today, and decline in frequency the further one moves from the Mediterranean. The farming pioneers in Europe, though initially successful, eventually encountered problems which led to population crashes. Then after the Neolithic, Europe had two great bursts of migration, both from fringe regions where farming had been adopted by foragers. One came from the European steppe in the Copper and Bronze Ages. The other was the spread of their Germanic and Slavic descendants in the Migration Period.

Most bizarre rationale for creating racial hybrids I've yet come across

On the second-to-last page of The $1,000 Genome, Kevin Davies recounts noticing two small children running around at the GET (Genomes, Environments, Traits) Conference:

They turned out to be [. . .] the children of Jong Bhak, the director of the Personal Genomics Institute in Korea, and his American (Caucasian) wife. They were also the youngest members of the genome sequencing club. "We wanted to know how different two siblings can be," said Bhak. "Our hybrid kids can give us some easy confirmation on that. They are brothers, but their genetic makeup will be much more different from each other than any two random people in the same population."

Nothing says "family" like "more different from each other than any two random people in the same population." In fairness, I'm not sure if Bhak is attempting to celebrate this fact, or merely acknowledging a reality that the vast majority of multiracialists no doubt fail to grasp.

Further update on People of the British Isles project

From their most recent newsletter (pdf):

We are pleased to tell you that we have just submitted our first scientific paper about the project. The main function of this paper is to announce PoBI to the scientific world and in it we show that, even with a relatively small number of samples and a few genetic markers, the samples we collected should be sufficient to detect genetic differences across the UK. [. . .]

One aspect that is of particular interest is the surnames we collected and we have spent some time with our collaborators at UCL (Professor Paul Longley and his group) dividing them into local and non-local surnames. The figure on the left shows a couple of examples. The idea is that individuals whose surname is local to an area are more likely to have family in that area for many generations than individuals whose surnames are found all over the country. This is obviously a generalisation, but it does seem that there are some genetic differences between sets of volunteers with local surnames and sets with non-local surnames and we are really looking forward to analysing all the data rather than just the small subset we have been studying so far. [. . .]

Our next priority is to analyse the 1.3 million genetic markers that have been typed on 3,000 of our volunteers [. . .] The data we analyse from these samples should shed light on the genetic impact of the different historical incursions into Britain. It is an extremely large data set and so it will take a while to analyse and write up. As mentioned in our last newsletter, 100 of our samples are having their complete DNA sequenced by the 1,000 Genomes Project (www.1000genomes.org) and it should not be too long before that very valuable information becomes available to us. [. . .]

As you will know from the last newsletter, the Wellcome Trust has given us funding for a further five years to look for genes involved in normal traits. The main focus is on facial features, but other traits include handedness, taste perception and skin colour. We have been going back to our volunteers to collect these data. We take 3D photographs of each volunteer’s face in order to identify genes involved in the control of particular facial features. Over the last 18 months, we have collected 475 such photographs and are beginning to analyse them with our collaborators in Surrey (Professor Josef Kittler and his group).

Last newsletter (pdf):

There is a great deal of interest in the genetics of facial features and, in addition, the frequency of genetic variants for facial features may well differ significantly between different parts of the UK. We will also be collecting data on a variety of other normal features including height, hair and skin colour, handedness, milk tolerance, musical preferences and perfect pitch, taste and smell preferences and features of the hand.

Victor Mair talk on Tarim Basin Mummies

Part of a series of lectures related to the "Secrets of the Silk Road" exhibition at the University of Pennsylvania Museum of Archaeology and Anthropology. The mummy and artifacts abruptly pulled from the exhibition by the Chinese government before it opened are back for now.

1000 Genomes Pilot Data Suggests Recent Selective Sweeps Rare in Human Lineage

Via GenomeWeb Daily News:

"Our findings suggest that recent human adaptation has not taken place through the arrival and spread of single changes of large effect, but through shifts of frequency in many places of the genome," co-senior author Mary Przeworski, a human genetics, ecology, and evolution researcher at the University of Chicago, said in a statement. "It suggests that human adaptation, like most common human diseases, has a complex genetic architecture."

Przeworski et al. Classic Selective Sweeps Were Rare in Recent Human Evolution. Science 18 February 2011: vol. 331 no. 6019 pp. 920-924. DOI: 10.1126/science.1198878

Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of “classic selective sweeps” (in which a beneficial mutation arises and rapidly fixes in the population).Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past ~250,000 years.

[. . .]

This conclusion does not imply that humans have experienced few phenotypic adaptations, or that adaptations have not shaped genomic patterns of diversity. Comparisons of diversity and divergence levels at putatively functional versus neutral sites, for example, suggest that 10 to 15% [and possibly as many as 40% (29)] of amino acid differences between humans and chimpanzees were adaptive [e.g., (30)], as were 5% of substitutions in conserved noncoding regions (22, 29) and ~20% in UTRs (22). Given the paucity of classic sweeps revealed by our findings, an excess of functional divergence would point to the importance of other modes of adaptation. One way to categorize modes of adaptation is in terms of their effect on the allele frequencies at sites that affect the beneficial phenotype. In this view, classic sweeps bring new alleles to fixation; selection on standing variation or on multiple beneficial alleles brings rare or intermediate frequency alleles to fixation; and other forms of adaptation, such as selection on polygenic traits, increase or decrease allele frequencies to a lesser extent. Such changes in allele frequencies can decrease variation at closely linked sites—to a lesser extent than in a full sweep—and might therefore contribute to a reduction in diversity near functional elements (31) as well as to excess divergence. Alternatives to classic sweeps are likely for parameters applicable to human populations (7, 32); in particular, many phenotypes of interest are quantitative and plausibly result from selection at many loci of small effect (8).

An important implication is that in the search for targets of human adaptation, a change in focus is warranted. To date, selection scans have relied almost entirely on the sweep model, either explicitly (by considering strict neutrality as the null hypothesis and a classic sweep as the alternative) or implicitly (by ranking regions by a statistic thought to be sensitive to classic sweeps and focusing on the tails of the empirical distribution). It appears that few adaptations in humans took the form that these approaches are designed to detect, such that low-hanging fruits accessible by existing approaches may be largely depleted. Conversely, the more common modes of adaptation likely remain undetected. Thus, to dissect the genetic basis of human adaptations and assess what fraction of the genome was affected by positive selection, we need new tests to detect other modes of selection, such as comparisons between closely related populations that have adapted to drastically different environments [e.g., (33)] or methods that consider loci that contribute to the same phenotype jointly [e.g., (34)]. Moreover, if alleles that contribute to recent adaptations are often polymorphic within a population, genome-wide association studies should be highly informative.

DNA USA: A Genetic Biography of America

Apparently not due out for another year, but here's what Bryan Sykes has been working on:

The best-selling author of The Seven Daughters of Eve now turns his sights on the United States, one of the most genetically variegated countries in the world. From the blue-blooded pockets of old-WASP New England to the vast tribal lands of the Navajo, Bryan Sykes takes us on a historical genetic tour, interviewing genealogists, geneticists, anthropologists, and everyday Americans with compelling ancestral stories. His findings suggest: Of Americans whose ancestors came as slaves, virtually all have some European DNA. Racial intermixing appears least common among descendants of early New England colonists. There is clear evidence of Jewish genes among descendants of southwestern Spanish Catholics. Among white Americans, evidence of African DNA is most common in the South. European genes appeared among Native Americans as early as ten thousand years ago. An unprecedented look into America's genetic mosaic and an impressive contribution to how we perceive race, this is a fascinating book about what it means to be American.

Also of possible interest: Viking DNA: The Wirral and West Lancashire Project (Stephen Harding, Mark Jobling, Turi King); Surnames, DNA, and Family History (George Redmonds, Turi King, David Hey).

Some links

Ahnenkult: Miscellaneous musings on the Ainu; race quotes

Hail: USA’s Total Fertility Rates by Race, 1980-2008; The Decline of Abortion

Genetic Future: On sharing genes with friends

Forward: Newer DNA Tests Uncover Hidden Jewish Bloodlines

JASON: The $100 Genome: Implication for the DoD (US Department of Defense) (pdf)

Genome Res.: Adaptive selection of an incretin gene in Eurasian populations

Haplotype structure analysis suggests that the derived allele at rs2291725 arose to dominance in East Asians ~8100 yr ago due to positive selection. The combined results suggested that rs2291725 represents a functional mutation and may contribute to the population genetics observation. Given that GIP signaling plays a critical role in homeostasis regulation at both the enteroinsular and enteroadipocyte axes, our study highlights the importance of understanding adaptations in energy-balance regulation in the face of the emerging diabetes and obesity epidemics.

PLoS ONE: Dissecting the Within-Africa Ancestry of Populations of African Descent in the Americas

MBE: The Genetic Structure of Domestic Rabbits

Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries.

Am J Hum Biol.: Substantial variation in qPCR measured mean blood telomere lengths in young men from eleven European countries

Controlling for age and case-control status, telomere lengths averaged 10.20 kilobases (interpolated from qPCR measures) across study centers and ranged from 5.10 kilobases in Naples, Italy to 18.64 kilobases in Ghent, Belgium-a greater than threefold difference across populations.

La antropología física y los «zoológicos humanos»: exhibiciones de indígenas como práctica de popularización científica en el umbral del siglo XX

All along the nineteenth century different anthropological exhibitions were held in many countries, in which people from a number of indigenous communities, especially transported from their homeland for the occasion, were exhibited publicly, both for citizenship's instruction and for specialists's "in vivo" studies on human biology. This paper presents a brief description of some of these scientific shows, and tries to relate them to contemporary human biology theories.

NYT: Heavy Doses of DNA Data, With Few Side Effects

John Hawks: Genomes too cheap to meter

J Pers Soc Psychol.: To be liked versus respected: Divergent goals in interracial interactions

Pervasive representations of Blacks and Latinos as unintelligent and of Whites as racist may give rise to divergent impression management goals in interracial interactions. We present studies showing that in interracial interactions racial minorities seek to be respected and seen as competent more than Whites do, whereas Whites seek to be liked and seen as moral more than racial minorities do.

Norwegian foundation plans ancient DNA analysis of Rollo descendants

The Explico Historical Research Foundation:

will attempt to find out if Rollo the Viking [male line ancestor of William the Conqueror] was Danish or Norwegian to settle a dispute that has been going on for centuries in Scandinavia. This we will do by retrieving DNA from corpses of his descendants.

They say they "hope to be able to perform our analysis by Easter 2011." The foundation's other projects include searching for remnants of the Celts in Turkey and Goths north of the Black Sea. More:

- Successfully conducted research on the Easter Island, proving South American origin for parts of the Easter Island population through genomic HLA typing. This research indicates strongly that some of the original Easter Island inhabitants some how migrated to the island from the east, from South America, and not only from Polynesia in the west, which has been the official story of Easter Island immigration. The research report by professor Erik Thorsby can be read here.

- On the Canary Islands contributed to the understanding of how the Canary Islands were originally settled and by whom (Pereira et al: Population expansion in the North African Late Pleistoscene signalled by mitochondrial DNA haplogroup U6. BMC Evolutionary Biology 2010 10:390). Also, DNA from a Royal Native lineage on the Canary Island La Gomera proves a connection most likely with the Basque, North Portugal or a British 'Celtic' connection.

- In Normandy, in our search for famous historical figures, closed in the lead on the patriach of William the Conqueror, the great Viking giant Rollo, in order to solve a close to thousand year old riddle about his origin. To be continued..

- In the Ukraine on Crimea and the Black Sea coast of Azov our successful 2006 expedition work is now continued in the labs, hopefully providing us with new vital knowledge on the ancient Greeks, who they were and whom today are most closely related to them.

- In the Caribbean we have worked hard on finding the DNA and especially the Y-chromosome lineage of Christopher Columbus' heritage. This work now seems to have paid off, giving us the opportunity to make new revelations about one of the worlds greatest explorers.

- Established good contact and made all preparations ready for field work in Northern Africa. We are awaiting the neccesary permissions to continue our scientific work in the Atlas Mountains.

- Continued our work in the different fields of expertise involving new technologies and our constant search for new discoveries. We are currently involved in projects in the Caribbean, the Ukraine, in Peru, Russia, Spain, France, Turkey, on Greenland and in Scandinavia. The new technologies we continue to make use of are foremost DNA and the mapping of Human Migrations and Georadar instruments for discovering treasures underground.

(Via the GENEALOGY-DNA list.)

Open thread (5)

For links, comments, suggestions, etc. Previous open threads: 1 2 3 4

Not skin deep

Basque communist Maju thinks this study indicates "patterns of inter-population differentiation are stronger in the genes of appearance mostly" and "the actual underlying differences between populations [. . .] are invariably much smaller than it looks".

But this is not what the paper shows at all. The single most highly population-differentiated gene group in the authors's analysis relates to pituitary gland development. Next comes dorsoventral neural tube patterning. Then some low-level cellular functions, more brain development, sperm motility and development, and thyroid gland development. Pigmentation comes about halfway down the list and hair follicle development below that.

The placement of pituitary- and thyroid-related genes near the head of the list brought to mind Carleton Coon's comments on endocrines and racial differences in temperament.

Why a dominant China could spark tribal warfare

A commenter links to an article in Foreign Policy which argues:

With China's new prominence in global affairs, the Han race, which constitutes 90 percent of the Chinese population, is suddenly the most dominant cohesive ethnic group in the world -- and it is seeking to remain that way through strategic alliances, aggressive trade policy, and attacks on racial minorities within the country's boundaries. The less tribally cohesive, more fragmented West is, meanwhile, losing out. [. . .]

Such primitive racial instincts were supposed to be long ago passé: We're supposed to be living in Thomas Friedman's "flat" world or Kenichi Ohmae's "borderless world." By now, supposedly, everyone is increasingly interconnected and undifferentiated. Affairs should be managed neatly by deracinated professionals, working on their iPads from Brussels, Washington, or any of the other "global" capitals.

But most people do not really see themselves as members of a large multinational unit, global citizens, or "mass consumers." Instead the drivers of history remain the essentials: the desire to feed one's family, support the health of the tribe, and shape the immediate community. The particularistic continues to trump the universalistic.

On differences within Europe:

The wigger mindset

A reader forwards a reference to this passage by Hebrew wigger / wigger expert William Upski Wimsatt. In line with my own perception of what motivates these types, Wimsatt acknowledges "romanticization of blacks was also a way to elevate myself":

Why does head form change in children of immigrants? A reappraisal.

More from Jantz on Boas:

CONCLUSIONS: The results support the two hypotheses tested. Change in Hebrew cranial indices resulted from abandoning the practice of cradling infants in America. U.S.-born Sicilian children experienced an environment worse than the one in Europe, and consequently experienced impaired growth. We conclude that the changes Boas observed resulted from specific behavioral and economic conditions unique to each group, rather than a homogeneous American environment.