Introduction

The use of ancient nucleic acids to infer population history and phylogeny is now entering its third decade, with the initial demonstration of the possibility and utility of the approach pioneered by Higuchi et al. (1984) on museum specimens of the extinct quagga, and by Pääbo (1985) on preserved soft tissue from Egyptian mummies. Now uniformly termed ancient DNA (aDNA) studies, the approach has exploded in the past decade to encompass studies of modern human origins, regional history and dynamics of prehistoric human populations, as well as phylogenetic studies of nonhuman organisms. A full review of this vast and rapidly growing literature is beyond the scope of this chapter, and interested readers are directed to several excellent and recent reviews of the field from a variety of disciplinary perspectives (e.g. Wayne et al., 1999; O'Rourke et al., 2000a; Hofreiter et al., 2001a; Kaestle and Horsburgh, 2002, Pääbo et al., 2004, Cipollaro et al., 2005).

The study of contemporary patterns of human genetic variation has proven a powerful approach to inferring human population history and evolution, although such approaches are bound by assumptions of evolutionary rates in the markers under study, effective population sizes over time, rates of population movement, levels of admixture, etc. The use of aDNA analyses in conjunction with such modern genetic studies affords a temporal perspective on human genetic variation that is, to some degree, independent of model assumptions.

What is anthropological genetics?

Anthropological genetics is a synthetic discipline that applies the methods and theories of genetics to evolutionary questions posed by anthropologists. These anthropological questions concern the processes of human evolution, the human diaspora out of Africa, the resulting patterns of human variation, and bio-cultural involvement in complex diseases. How does anthropological genetics differ from its kin discipline, human genetics? Both fields examine various aspects of human genetics but from different perspectives. With the synthetic volume of 1973 (Methods and Theories of Anthropological Genetics), it became evident that the questions posed by the practitioners of anthropological genetics and human genetics tended to be somewhat different. I compared and contrasted these two fields in the introduction to the special issue of Human Biology (2000) on Anthropological Genetics in the twenty-first century (see Table 1.1). What distinguishes anthropological genetics from human genetics is its emphasis on smaller, reproductively isolated, non-Western populations, plus a broader, biocultural perspective on evolution and on complex disease etiology and transmission. Judging from the contents of the American Journal of Human Genetics (premiere journal in the field of human genetics) there is a greater emphasis on the causes and processes associated with disease, and the examination of these processes in affected phenotypes (probands) and their families. Anthropological geneticists tend to focus more on normal variation in non-Western reproductively isolated human populations (Crawford, 2000).

The peopling of the Pacific is particularly fascinating as it involves one of the earliest migrations of modern humans, the settlement of Australia and New Guinea, and the last major colonization event, the settlement of Polynesia. It required crossing vast distances of open ocean in small double-hulled canoes, suggesting highly developed sailing and navigational skills. The deep chronology, combined with the variations in Pacific environments, make the Pacific an ideal region to study colonization, adaptation, human genetics and human biology. This is not because islands represent laboratory conditions (Vayda and Rappaport, 1963), but because Pacific islands represent a range of environments and, perhaps, unique historical conditions that allow us to study the many factors that affect human variation.

The general geographic setting has significant implications for the settlement history and human biology in any region, but this is dramatically so in the Pacific. Most people are familiar with the original biogeographic dissection of the Pacific into Melanesia, Polynesia and Micronesia. While these crudely descriptive terms define the three regions as the ‘black islands’, ‘many islands’ and ‘small islands’, this familiar system of classification makes no sense in terms of biology, language and culture. So, prehistorians like Roger Green and others (Pawley and Green, 1973; Green, 1991; Kirch, 2000) have suggested an alternative system identifying two significant regions in the Pacific, Near Oceania and Remote Oceania, shown in Figure 14.1. This classification is based primarily on colonization history and, therefore, has biological, cultural and linguistic significance.

Introduction

This chapter may seem to some to be a fond remembrance of things past. Given the increasing wealth of new data on genetic variation in humans, it might seem rather old-fashioned to deal with quantitative traits. Long before the discovery of blood groups, protein and enzyme polymorphisms, and DNA sequences, the only way anthropologists could describe human variation was in terms of quantitative traits, such as anthropometrics. In the broadest sense, a quantitative trait is one whose genotypic and/or phenotypic distribution is continuous, such as stature or head length, rather than discrete, such as a blood type or a DNA haplotype. Quantitative traits are often referred to as ‘complex traits’ because the phenotype is a reflection of both genetic and non-genetic influences, the latter of which can include age, diet and climate, as well as many other factors. Some quantitative traits, such as the level of phenylalanine in the blood, are due to a single gene whose phenotypic expression is affected by environmental (non-genetic) influences resulting in a continuous distribution. Other traits, such as cleft palate, are phenotypically discrete, but reflect an underlying continuous genotypic distribution under a threshold model. Most quantitative traits examined in the course of anthropological research are assumed to be polygenic, where a continuous distribution (often reflecting a normal distribution) is a function of multiple genes and environmental influences (Cavalli-Sforza and Bodmer, 1971). The primary focus of this chapter is on polygenic quantitative traits and their application to questions of population structure and history.

Researchers in anthropology, epidemiology, and human genetics have been investigating the sources of human variation and the etiology of human diseases over the past century, largely independently of one another, using very different methodologies to study environmental factors, infectious agents, genetic variation, and their respective effects on human phenotypic variation. Human geneticists have had success in identifying DNA sequence variations which ‘cause’ a variety of clearly inherited ‘Mendelian’ conditions (Terwilliger and Goring, 2000), similar to the successes of epidemiologists in identifying ‘causal’ risk factors which by themselves dominated the trait's etiology. However, once many of the major ‘sledgehammer’ risk factors were identified for each of these flavours of risk factor (genetic, environmental, and infectious), researchers began to focus in earnest on the more complex family of common traits related to normal variation, which are of predominant public health relevance, and which are hypothesized to be influenced in a small way by each of numerous risk factors, potentially of each type (Weiss and Terwilliger, 2000) – that is to say epidemiologists and human geneticists have been moving into areas where anthropologists have been for decades, applying a new set of tools to old problems. However, the standard toolkit of epidemiologists and medical geneticists are not the most appropriate for this problem, as anthropologists have been aware for a long time, and this application of unmodified tools from classical health science has been very difficult to translate to studies of normal variation in humans, since the etiology is much more complex.

Introduction

There are many parallels between anthropological genetics and forensic science. Both have evolved as new useful human polymorphisms were found. Both have evolved as technology has advanced. See the excellent coverage of this in Chapter 7. The approaches of anthropological genetics to the study of human populations is described in Chapter 7. In contrast to anthropological genetics which usually looks at the population, forensic science uses the genetically useful markers found in populations to characterize or in forensic terminology ‘individualize’ evidence and individuals. In the ideal sense both would like to have genetic markers that will either individualize populations or evidence to a given population of geographical origin. In forensic science the area that tests biological testing of evidence is called forensic genetics. In forensic genetics there are two general ways in which evidence is individualized. The first is done by direct comparison of two genetic profiles; the second is done using Mendelian inheritance to establish the genetic relationship.

Forensic science uses a process of comparison in which an unknown sample is always compared to a known or reference sample. In the case of identification of drugs a white powder suspected of being a controlled substance is seized by a police officer and submitted to the crime laboratory for identification. The laboratory will do a presumptive test to see if the powder could be a controlled substance.

An old problem

America's ‘discovery’ by the Europeans of the fifteenth century posed a question: who were the strange people who inhabited the land? A papal bull from Paul III (1468–1549) solemnly recognized in 1537 their human status. Since they were humans they could only be descendants of Adam and Eve, more specifically of Noah's grandchildren. Arias Montanus was able to find a resemblance between the words Peru and Ophir, one of Noah's descendants, therefore setting the question of their origin, at least in biblical terms (Pericot y García, 1962; Lavallée, 2000)

Equally bizarre was Florentino Ameghino's contention that all humanity had originated from the Argentinian Pampean region. Most of these suggestions or hypotheses that were put forward before the twentieth century or early in the 1900s have now only historical (or mythological) interest. Some of them have been summarized in Salzano and Callegari-Jacques (1988) and Crawford (1998). Since no paleoanthropological findings of high antiquity were found in America the questions were centred on three basic issues: (a) from where did the Amerindians come? (b) how many waves of immigration occurred?, and (c) when did they arrive? Researchers from different disciplines considered these questions and diverse, sometimes contradictory answers had been made. They will be considered in the following sections.

The colonization process: non-genetic evidences

Geology and archaeology

The present consensus is that the prehistoric colonization of the New World should have occurred via the Bering Land Bridge, formed as a result of lower sea levels which were present there at the time.

Abstract

Comparative studies of ethnically diverse human populations are important for testing historical hypotheses relating to the origin and dispersal of modern humans. In this chapter, we summarize the competing theories about how, when and where modern humans originated. We describe levels and patterns of genetic diversity across modern human populations and review the genetic evidence concerning modern human origins. We also discuss genetic signatures of population migrations within and out of Africa by contrasting and comparing these genetic signatures with global patterns of genetic diversity. Finally, we discuss implications of molecular data for reconstructing the demographic histories of African and non-African populations.

Introduction

The origin and dispersal of modern humans across the globe remains a topic of considerable interest and debate. While this topic has historically been within the realm of paleoanthropology based on fossil and archeological data, this topic is now being addressed in the fields of genetics and molecular biology. Genetic data, primarily gene frequency variation at polymorphisms, have been used to examine population similarities since the study of ABO blood type frequencies by Hirszfeld and Hirszfeld in 1919 (Hirszfeld and Hirszfeld, 1919). In the subsequent decades, hundreds of populations have been studied for blood group loci, serum protein polymorphisms, and various enzyme electrophoretic polymorphisms (Cavalli-Sforza et al., 1994). The advent of molecular biology techniques, including Restriction Fragment Length Polymorphisms (RFLPs) and Polymerase Chain Reaction (PCR) in the 1980s, mtDNA sequence variation in the 1980s, and nuclear sequence variation, Single Nucleotide Polymorphisms (SNPs), Short Tandem Repeat Polymorphisms (STRPs), and Alu polymorphisms in the 1990s until present, have made it feasible to do much more detailed, high-throughput studies of the distribution of molecular variation in globally diverse human populations.

Introduction

The relationship between demography and evolution is close and long-standing. After all, it was by reading Malthus' (1798) essay on population that both Darwin and Wallace achieved their insight into natural selection. The importance of demography for anthropological genetics continues to be strong. Anthropological genetics, concerned with understanding the patterns and causes of genetic variation within and among populations, depends on anthropological demography to provide data on population sizes and fluctuations, mating structure, and migration patterns and histories that are crucial for that understanding.

While demographers study many aspects of human populations (Preston et al., 2001; Siegel and Swanson, 2004), anthropological demography usually focuses on small-scale populations and is often linked with studies of human biology. Anthropological demographic studies have been undertaken expressly to provide information necessary to understand genetic variation.

Demography is the study of human population. More specifically, as the classic definition states: ‘Demography is the study of the size, territorial distribution, and composition of population, changes therein, and the components of such change’ (Hauser and Duncan, 1959: 31). The size and composition of a population is caused by three fundamental factors: fertility (births), mortality (deaths), and migration (in-migration and out-migration). The discipline of demography has historically emphasized measurement and description of these vital processes, usually at the macro level of the national population. It is generally the population characteristics of countries that are analysed and compared (e.g. see Keyfitz and Fleiger, 1968).

Introduction

Field research helps us answer some basic, almost universal, questions: ‘Who are we? Where did we come from? ‘How did we get here?’

As discussed in Chapter 1 of this volume, anthropological genetics was formalized as a field of investigation during the 1970s and 1980s, with the twin foci of genetic structure of human populations and genetic-environmental interactions in the dissection of the genetic architecture of complex phenotypes (Crawford, 2000b). What distinguishes anthropological genetics from human genetics is its emphasis on smaller, reproductively isolated, non-Western populations, plus a broader, biocultural perspective on complex disease etiology and transmission. Similarly, the reconstruction of the human diaspora and the phylogeny of our species, based on molecular genetic markers, required comparisons among human populations widely dispersed geographically. As a result of these foci, field research became an integral part of anthropological genetics and provided considerable insight into the understanding of human variation and disease processes.

This chapter summarizes the following aspects of field investigations: (1) The reasons for conducting field research in anthropological genetics. For most of us the air-conditioned laboratory is a much more comfortable place to conduct research than in some hot, tropical jungle, where you become part of the insect's food chain, or the frigid North with cold stress and summer mosquitoes. Why expose yourself to the risks of the hot sun and voracious insects if you can answer basic anthropological genetics questions in the relative comfort of your laboratory? (2) Describes the preparation necessary for developing a field programme.

Introduction

In the post-genomic era, the genetic analysis of common diseases will be one of the most critically important areas of biomedical science. Over the past two decades, it has become clear that many of the diseases that constitute the major public health burden in the United States – diseases such as diabetes, atherosclerosis, obesity, hypertension, depression, alcoholism, osteoporosis, and cancer – have a substantial genetic component. The genetic architecture of such diseases is complex, however, involving multiple genetic and environmental components and their interactions. The specific quantitative trait loci (QTLs) that are involved in the biological pathways of these diseases, and the individual effects of these QTLs in the general population, are still largely unknown. The stochastic complexity of the genotype-phenotype relationship of a common disease requires that statistical inference plays a prominent role in the dissection of the underlying genetic architecture. However, statistical genetic methods suitable for this immense task are still in their infancy. The genomic localization and identification of QTLs and characterization of their causal functional polymorphisms will require new advanced statistical genetic tools.

Over the past decade, we have been successful in developing the theoretical and empirical foundation requisite to a thorough understanding of the strengths and weaknesses of variance component-based quantitative trait linkage methods. We have incorporated many of our statistical genetic developments into our freely available computer package, SOLAR (Sequential Oligogenic Linkage Analysis Routines) (Almasy and Blangero, 1998).

Introduction

In 1973, a chapter entitled ‘The use of genetic markers of the blood in the study of the evolution of human populations’, was published in the first volume that attempted to synthesize the field of anthropological genetics (Crawford, 1973). This chapter defined genetic markers as "discrete segregating, genetic traits which can be used to characterize populations by virtue of their presence, absence, or high frequency in some populations and low frequency in others' (Crawford, 1973: 38). This definition similarly applies to molecular markers, which are segregating regions of DNA, present in some populations but absent or infrequent in others. The 1973 chapter summarized the available genetic markers of the blood that could be used for the measurement of evolutionary processes and the characterization of human population structure. The list of available polymorphic loci included 16 blood groups, 11 red blood cell proteins, 10 serum proteins and 3 white cell and platelet systems. These ‘riches’ of available variation of the blood followed 70 years of research on the blood group systems (since Karl Landsteiner's original work in 1900), and Oliver Smithies (1955) development of zone electrophoresis for the separation of specific proteins from mixtures such as the serum of the blood (Landsteiner and Levine, 1927). At the time the first volume in anthropological genetics was compiled, the physiological functions of blood groups were unknown, other than their involvement in blood transfusion and some suspect statistical associations with disease.