John H. Relethford

Prevalence of Diabetes in Mexican Americans: Relationship to Percent of Gene Pool Derived from Native American Sources

We have estimated the prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in Mexican Americans and Anglos in three San Antonio neighborhoods. The age-adjusted NIDDM rates (both sexes pooled) for Mexican Americans were 14.5%, 10%, and 5% for residents of a low-income barrio, a middle-income transitional neighborhood, and a high-income suburb, respectively. In Mexican American women, though not in men, obesity also declined from barrio to suburbs. We have previously shown, however, that, although obesity is an important cause of NIDDM in Mexican Americans, there is a two- to fourfold excess in the rate of NIDDM in this ethnic group over and above that which can be attributed to obesity. We therefore speculated that genetic factors might also contribute to excess NIDDM in this ethnic group. The percent native American admixture of Mexican Americans as estimated from skin color measurements was 46% in the barrio, 27% in the transitional neighborhood, and 18% in the suburbs. The NIDDM rates in Mexican Americans thus paralleled the proportion of native American genes. Furthermore, the San Antonio Mexican American rates were intermediate between the NIDDM rates of “fullblooded” Pima Indians (49.9%), who presumably have close to 100% native American genes, and the San Antonio Anglo population (3.0%) and the predominantly Anglo HANES II population (3.1%), both of which presumably have few if any native American genes. The association of genetic admixture with NIDDM rates suggests that much of the epidemic of NIDDM in Mexican Americans is confined to that part of the population with a substantial native American heritage.

Global Patterns of Isolation by Distance Based on Genetic and Morphological Data

The isolation-by-distance model predicts that genetic similarity between populations will decrease exponentially as the geographic distance between them increases, because of the limiting effect of geographic distance on rates of gene flow. Many studies of human populations have applied the isolation-by-distance model to genetic variation between local populations in a limited geographic area, but few have done so on a global level, and these few used different models and analytical methods. I assess genetic variation between human populations across the world using data on red blood cell polymorphisms, microsatellite DNA markers, and craniometric traits. The isolation-by-distance model provides an excellent fit to average levels of genetic similarity within geographic distance classes for all three data sets, and the rate of distance decay is the same in all three. These results suggest that a common pattern of global gene flow mediated by geographic distance is detectable in diverse genetic and morphological data. An alternative explanation is that the correspondence between genetic similarity and geographic distance reflects the history of dispersal of the human species out of Africa.

Hemispheric difference in human skin color

Previous studies of human skin color have shown a strong relationship between skin color and distance from the equator, which has been interpreted as a link between skin color, latitude, and the intensity of ultraviolet radiation. The underlying assumptions are that UV radiation is greatest at the equator and that it diminishes with increasing latitude to the same extent in both the Northern and Southern Hemispheres. The standard analysis of human skin color is based on these assumptions, such that skin color is assumed to be darkest at the equator, and the decrease of skin color with latitude is assumed to be the same in both hemispheres. A nonlinear piecewise regression model was developed to test these assumptions and applied to mean skin reflectance data from 102 male samples and 65 female samples from across the Old World. For both males and females, skin reflectance (%) is lowest at the equator (darkest skin). Among males, skin reflectance increases roughly 8.2% for every 10 degrees of latitude in the Northern Hemisphere but only 3.3% for every 10 degrees of latitude in the Southern Hemisphere. Among females, the corresponding numbers are 8.1% in the Northern Hemisphere and 4.7% in the Southern Hemisphere. These results indicate that human skin color is darker in the Southern Hemisphere than in the Northern Hemisphere at equivalent latitude. Recent research shows that UV radiation is higher in the Southern Hemisphere than in the Northern Hemisphere at similar latitude. This difference, relating to astronomical and climatic conditions, may have existed in the past at different times and perhaps influenced the evolution of human skin color.

Race and global patterns of phenotypic variation

Phenotypic traits have been used for centuries for the purpose of racial classification. Developments in quantitative population genetics have allowed global comparison of patterns of phenotypic variation with patterns of variation in classical genetic markers and DNA markers. Human skin color shows a high degree of variation among geographic regions, typical of traits that show extensive natural selection. Even given this high level of geographic differentiation, skin color variation is clinal and is not well described by discrete racial categories. Craniometric traits show a level of among-region differentiation comparable to genetic markers, with high levels of variation within populations as well as a correlation between phenotypic and geographic distance. Craniometric variation is geographically structured, allowing high levels of classification accuracy when comparing crania from different parts of the world. Nonetheless, the boundaries in global variation are not abrupt and do not fit a strict view of the race concept; the number of races and the cutoffs used to define them are arbitrary. The race concept is at best a crude first-order approximation to the geographically structured phenotypic variation in the human species.

Genetic evidence for larger African population size during recent human evolution

Genetic evidence suggests that the long-term average effective size of sub-Saharan Africa is larger than other geographic regions. A method is described that allows estimation of relative long-term regional population sizes. This method is applied to 60 microsatellite DNA loci from a sample of 72 sub-Saharan Africans, 63 East Asians, and 120 Europeans. Average heterozygosity is significantly higher in the sub-Saharan African sample. Expected heterozygosity was computed for each region and locus using a population genetic model based on the null hypothesis of equal long-term population sizes. Average residual heterozygosity is significantly higher in the sub-Saharan African sample, indicating that African population size was larger than other regions during recent human evolution. The best fit of the model is with relative population weights of 0.73 for sub-Saharan Africa, 0.09 for East Asia, and 0.18 for Europe. These results are similar to those obtained using craniometric variation for these three geographic regions. These results, combined with inferences from other genetic studies, support a major role of Africa in the origin of modern humans. It is less clear, however, whether complete African replacement is the most appropriate model. An alternative is an African origin with non-African gene flow. While Africa is an important region in recent human evolution, it is not clear whether the gene pool of our species is completely out of Africa or predominately out of Africa.

Global analysis of regional differences in craniometric diversity and population substructure.

Estimates of genetic diversity in major geographic regions are frequently made by pooling all individuals into regional aggregates. This method can potentially bias results if there are differences in population substructure within regions, since increased variation among local populations could inflate regional diversity. A preferred method of estimating regional diversity is to compute the mean diversity within local populations. Both methods are applied to a global sample of craniometric data consisting of 57 measurements taken on 1734 crania from 18 local populations in six geographic regions: sub-Saharan Africa, Europe, East Asia, Australasia, Polynesia, and the Americas. Each region is represented by three local populations. Both methods for estimating regional diversity show sub-Saharan Africa to have the highest levels of phenotypic variation, consistent with many genetic studies. Polynesia and the Americas both show high levels of regional diversity when regional aggregates are used, but the lowest mean local population diversity. Regional estimates of FST made using quantitative genetic methods show that both Polynesia and the Americas also have the highest levels of differentiation among local populations, which inflates regional diversity. Regional differences in FST are directly related to the geographic dispersion of samples within each region; higher FST values occur when the local populations are geographically dispersed. These results show that geographic sampling can affect results, and suggest caution in making inferences regarding regional diversity when population substructure is ignored.

Genetic evidence and the modern human origins debate

A continued debate in anthropology concerns the evolutionary origin of ‘anatomically modern humans’ (Homo sapiens sapiens). Different models have been proposed to examine the related questions of (1) where and when anatomically modern humans first appeared and (2) the genetic and evolutionary relationship between modern humans and earlier human populations. Genetic data have been increasingly used to address these questions. Genetic data on living human populations have been used to reconstruct the evolutionary history of the human species by considering how global patterns of human variation could be produced given different evolutionary scenarios. Of particular interest are gene trees that reconstruct the time and place of the most recent common ancestor of humanity for a given haplotype and the analysis of regional differences in genetic diversity. Ancient DNA has also allowed a direct assessment of genetic variation in European Neandertals. Together with the fossil record, genetic data provide insight into the origin of modern humans. The evidence points to an African origin of modern humans dating back to 200 000 years followed by later expansions of moderns out of Africa across the Old World. What is less clear is what happened when these early modern humans met preexisting ‘archaic human’ populations outside of Africa. At present, it is difficult to distinguish between a model of total genetic replacement and a model that includes some degree of genetic mixture.

Local Extinction and Recolonization, Species Effective Population Size, and Modern Human Origins

Abstract A primary objection from a population genetics perspective to a multiregional model of modern human origins is that the model posits a large census size, whereas genetic data suggest a small effective population size. The relationship between census size and effective size is complex, but arguments based on an island model of migration show that if the effective population size reflects the number of breeding individuals and the effects of population subdivision, then an effective population size of 10,000 is inconsistent with the census size of 500,000 to 1,000,000 that has been suggested by archeological evidence. However, these models have ignored the effects of population extinction and recolonization, which increase the expected variance among demes and reduce the inbreeding effective population size. Using models developed for population extinction and recolonization, we show that a large census size consistent with the multiregional model can be reconciled with an effective population size of 10,000, but genetic variation among demes must be high, reflecting low interdeme migration rates and a colonization process that involves a small number of colonists or kin-structured colonization. Ethnographic and archeological evidence is insufficient to determine whether such demographic conditions existed among Pleistocene human populations, and further work needs to be done. More realistic models that incorporate isolation by distance and heterogeneity in extinction rates and effective deme sizes also need to be developed. However, if true, a process of population extinction and recolonization has interesting implications for human demographic history.

Population structure and anthropometric variation in rural western Ireland: Migration and biological differentiation

Models of population structure can be investigated using data on anthropometric variation among local populations. Anthropometric data collected by Dupertuis and Dawson during the 1930s were analysed from 347 males and 261 females in 12 towns in three counties of western Ireland. We hypothesized that recent migration would decrease the degree of among-group variation. To test this hypothesis, two additional samples were created by excluding known inter-county migrants from both male and female samples. Based on ethnographic data, a fifth sample was created using unmarried females only, in order to control partially for local migration upon marriage. Univariate and multivariate measures of relative differentiation were developed to compare different levels of migration and differences among the sexes. We found that the degree of among-group variation decreased as the amount of migration increased, in accordance with spatial models of population structure. Using non-parametric correlations of geographic and anthropometric distance, the observed patterns of differentiation were closely related to geography, suggesting a spatial model of gene flow to be appropriate in interpreting among-group variation. The female samples showed greater differentiation and higher correlations with geography than the males. It seems that this results from the sensitivity of males to developmental and local environmental influences, causing an increase in the relative amount of within-group variation.

Models, predictions, and the fossil record of modern human origins

It is clear from the recent contents of this journal and others that the debate about modern human origins continues unabated. My own foray into this subject has dealt with some of the genetic evidence. It has become increasingly clear to me that much of the genetic evidence is indeterminate and that both African replacement and multiregional models can explain observed patterns of genetic variation.1,2 Consider, for example, the finding that many traits show higher genetic diversity within sub-Saharan African populations. While this finding can be interpreted as indicating a greater age for African populations, thus supporting a recent African origin, it can also be explained by a larger long-term African population size, which is compatible with both a recent African origin and multiregional evolution. Population geneticists have long known of the problems of unraveling population history from genetic data. Relationships between populations can reflect either common ancestry or migration.3–7 When considering the predictions of different models, it is critical to make sure that the predictions are unique to each model. I suggest that the problem of indeterminate results is also characteristic of some analyses of the fossil record. In particular, the results from several studies proclaimed as proof of a recent African origin are also compatible with a multiregional model. One approach to analyzing the fossil record has been to compare fossil samples from different geographic regions across time by using some form of biological distance measure.8–11 A useful comparison would be between fairly recent modern human fossil samples (,30 kya) and earlier samples (35 to 1001 kya) across the major geographic regions of the Old World.10,11 The most relevant distances are those across time periods. Are the distances within regions less than the distances between regions? Several analyses have shown that more recent modern samples are morphologically more similar to earlier samples from Africa and the Middle East than to earlier samples within their geographic region. For example, it has been suggested that recent modern samples from Europe (e.g., Cro-Magnon) are more similar to older samples from Africa and the Skhul-Qafzeh samples in the Middle East than to earlier Europeans (Neandertals).8–11 These findings are often taken as support for a recent African origin because this is the type of pattern we would expect to see if all recent modern humans came from Africa within the last 100,000 years. I will not discuss here debates over sample composition, measurements used, or specifics of chronology. My purpose is to examine the underlying assumptions of such studies, and to that end I will take the reported distances as given. Further study can always help us refine our measurements and analyses, but this is of little utility if we do not examine underlying assumptions and make sure that our interpretations are based on valid predictions of the models. Assuming that the distances between fossil samples across time and space are an accurate reflection of past history, it is clear that such results are compatible with a recent African origin. This finding would reject a multiregional model only if the results do not agree with the predictions of a multiregional model. What are these predictions? It is common to see statements to the effect that multiregional evolution predicts that the greatest similarity across time will be within geographic regions. According to this prediction, recent Europeans should be more similar to Neandertals than are fossil samples from other regions at roughly the same time period. This assumption is apparent in Waddle’s design matrix for the multiregional model, in which she predicts that the smallest biological distances will occur within geographic regions.10 The assumption was made most recently with reference to the extraction of Neandertal mitochondrial DNA:12 Krings and colleagues stated that ‘‘whereas the Neandertals inhabited the same geographic region as contemporary Europeans, the observed difference between the Neandertal sequence as modern Europeans do not indicate that it is more closely related to modern Europeans than to any other population of contemporary humans.’’ At first glance, this assumption seems to make sense. After all, given that multiregional evolution incorporates isolation by distance, we would expect, in any given generation, a pattern of population endogamy. At an aggregate level, this would translate into regional endogamy, so that the vast majority of a generation’s genes would come from ancestors one generation earlier in the same geographic region. It is then assumed that the accumulated ancestry over many generations would reflect this pattern, so John H. Relethford, Department of Anthropology, State University of New York College at Oneonta, Oneonta, NY 13820.