Summary: the Science of Genealogy by Genetics

Developing World Bioethics ISSN 1471-8731 (print); 1471-8847 (online) Volume 3 Number 2 2003

SUMMARY: THE SCIENCE OF GENEALOGY BY GENETICS

JOSEPHINE JOHNSTON AND MARK THOMAS

ABSTRACT This summary lays out the basic science and methodology used in genetic testing that investigates historical population migrations and the ancestry of living individuals. The genetic markers used in this testing, and the dis- tinction between Y-chromosome, mitochrondial and autosomes analysis, are explained and the shortcomings of these methodologies are explored.

Anthropology has a new tool. In addition to studying human evolution and population migrations through the analysis of archae- ological sites, languages and physical traits, anthropologists can now use genetics to illuminate our ‘pre-history.’ Precursor work in this area was carried out in the 1950s by Italian geneticist Luigi Luca Cavalli-Sforza, who designed a study using blood types to test the theory of genetic drift. Genetic drift is often posited in oppo- sition to natural selection to explain why certain genetic traits change their frequency in a population over time. The theory pre- dicts that some genetic variants become more common in the gene pool purely by chance because some people have large numbers of offspring whilst others do not. In this way, an individual living in a small isolated community can ‘ﬂood’ the community with his or her distinctive genetic traits.1 To test this theory Cavalli-Sforza compared the blood groups (A, B, O and Rh) of small, isolated mountain communities around Parma, Italy, with those of nearby communities living on the plains. He found that the distribution of blood types differed less widely on the plains than in the mountain villages, as genetic drift would predict.2 The

1 S. Olson. 2002. Mapping Human History: Discovering the Past Through Our Genes. New York. Houghton Mifﬂin: 164–165. 2 L.L. Cavalli-Sforza. ‘Genetic Drift’ in an Italian Population. Scientiﬁc American 1969; 221: 30–37.

© Blackwell Publishing Ltd. 2003, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA. 104 JOSEPHINE JOHNSTON AND MARK THOMAS beauty of Cavalli-Sforza’s experiment is that it points to a new way of following, and distinguishing between, populations as they move across the world. But blood groups are large categories, so there was much excitement when scientists began to isolate DNA, allowing genetic anthropologists to compare DNA markers instead of blood groups across populations. The initial work in this area looked at mitochrondial DNA, and then later the Y-chromosome, but it has also spread to other areas of the human genome. In order to understand how genetic anthropologists have used the new genetics to follow populations across the globe and to postulate relationships between populations, it is necessary to have a basic understanding of the science itself.

OUR GENETIC MAKEUP In the nucleus of almost all human cells are 46 tiny structures called chromosomes. These chromosomes are mostly made up of deoxyribonucleic acid or DNA, which comprises four chemical bases: adenine, thymine, cytosine, and guanine. The chrom somes in the cell nucleus are grouped in pairs – 23 pairs in all. One member of each pair has come from the mother of the individual and the other member from the father. Of the 23 pairs, 22 are essentially identical to each other. The 23rd pair is either a pair of X-chromosomes, if the individual is female, or an X- chromosome and a Y-chromosome, if the individual is male. When humans produce sperm and eggs, the chromosome pairs separate and the egg or sperm receives only one member of each pair (each sperm has 22 chromosomes plus either an X- chromosome or a Y-chromosome, and each egg contains 22 chromosomes plus an X-chromosome). Before the chromosomes separate in this way the pairs swap pieces of their DNA with each other. In women this process happens with all the chromosome pairs including the X pair. However, because the X- and the Y- chromosomes in a man are so different, they swap almost no DNA with each other when they separate. When the sperm and the egg join together in fertilisation, the individual chromosomes pair up again. Sometimes mistakes are made when DNA is copied during the production of cells, sperm, and eggs. These mistakes are called mutations and lead to differences in our DNA called polymorphisms. Some polymorphisms will result in the death of the cell or organism, or prevent the organism from breeding. However, many polymorphisms have no adverse effects on us and they are

© Blackwell Publishing Ltd. 2003 SUMMARY: THE SCIENCE OF GENEALOGY BY GENETICS 105 simply copied and handed down to the next generation. DNA can mutate in different ways and different types of mutation can have different rates of occurrence. Indeed, some kinds of mutation are so rare that when we observe a polymorphism at a particular site on a chromosome, we can assume that it is a result of a single mutation event in human history. The arrangement of different kinds of polymorphisms with different rates of occurrence, linked together on the same chromosome, is known as a haplotype. Because most of the Y-chromosome does not swap material with the X-chromosome, the Y-chromosome in a man’s sperm will be an almost exact copy of the Y-chromosome in his body’s cells. Any sons the man fathers will also carry this same Y-chromosome, com- plete with that man’s polymorphisms. As scientists know approxi- mately how often certain kinds of mutations occur they can look for these and determine how closely related any two men are through the male line. The more Y-chromosome differences two men have, the less recently they had a common male-line ancestor. Y-chromosomes in men living today thus retain a record of the chromosome’s passage through time. They can reveal paternal ancestry and show relationships between different groups of men.3 It is not just men who retain a record of their genetic ancestry. Women also carry a record of their history in their mitochondrial DNA, which is outside the cell’s nucleus in the mitochondria where the cell’s energy is produced. Following fertilisation of an egg, the sperm’s mitochondria are discarded and only the mitochondria from the mother are retained in the new cell. Therefore, the DNA in each person’s mitochondria is a unique record of his or her maternal heritage. Like the Y-chromosome, mitochondrial DNA can also include polymorphisms, which scientists can use to con- struct extended mother-to-daughter genealogical trees.4 The same principles apply to the autosomes (chromosomes other than the X and the Y), but making sense of autosomal genetic differences is much more difﬁcult for two reasons. First, we all have two versions of each autosome, one from our mother and one from our father. Because standard genetic testing methods do not tell us which of the two chromosomes a polymorphism is on, it is difﬁcult to work out the order of polymorphisms on an individual chromosome. Second, autosomes are

3 M.G. Thomas, T. Parﬁtt, D.A. Weiss, K.I. Skorecki, J.F. Wilson, M. LeRoux, N. Bradman & D.B. Goldstein. Y Chromosomes Traveling South: The Cohen Modal Haplotype and the Origins of the Lemba – The ‘Black Jews of South Africa’. American Journal of Human Genetics 2000; 66: 674–686. 4 N. Bradman & M. Thomas. Why Y? The Y Chromosome in the Study of Human Evolution, Migration and Prehistory. Science Spectra 1998; 14: 32–37.

© Blackwell Publishing Ltd. 2003 106 JOSEPHINE JOHNSTON AND MARK THOMAS more difficult to interpret because they readily recombine. Thus, while one of a pair of chromosomes may have come from our mother, she will have inherited parts of that chromosome from her mother and parts from her father. The same will apply to autosomes we inherited from our father. As a result we cannot represent the ancestry of a whole autosomal chromosome as a simple genealogical tree (as we can with the mitochondrial DNA or the Y-chromosome). Methods do exist for analysing genetic differences on autosomes, but they tend to rely heavily on complex sta- tistics. Indeed, we can make use of what is sometimes considered the nuisance of recombination in genetic anthropology to show that populations have either been genetically isolated or are part of a large and old population. One good reason to look at autosomes is that they contain the vast majority of our DNA, and as a result contain more information on the relationships of people and populations. Another reason is that the polymorphic variation present on autosomes represents a multitude of different but overlapping genealogical (gene) trees, whereas variation on the Y-chromosome and mtDNA represent only two (the male-specific and female-specific) genealogical trees. Unfortunately, a single or small number of gene trees will not always reflect the relationships of populations. If we want to build up a reliable picture of population history we need to look at many gene trees at the same time.

GENETIC ANTHROPOLOGY Using these new genetic tools, studies have been undertaken to show that the African Lemba may have Jewish ancestry,5 to give clues to the ancestral home of African Americans,6 to show that some descendents of the slave Sally Hemmings were probably fathered by Thomas Jefferson,7 and to conﬁrm the legend that the Maori arrived in New Zealand in one planned migration.8

5 Thomas et al., op. cit. note 3. 6 C. Goldberg. DNA Offers Link to Black History. The New York Times 28 August, 2000. Available online: http://www.bumc.bu.edu/Departments/ PageMain.asp?Page=5165&DepartmentID=350 (accessed 7 November, 2002). 7 E.A. Foster, M.A. Jobling & P.G. Taylor. Jefferson Fathered Slave’s Last Child. Nature 1998; 396: 27–28. 8 R.P. Murray-McIntosh, B.J. Scrimshaw, P.J. Hatﬁeld & D. Penny. Testing Migration Patterns and Estimating Founding Population Size in Polynesia by using Human mtDNA Sequences. Proceedings of the National Academy of Sciences 1998; 95: 9047–9052.

In fact, scientists across the world are using genetic testing to study the ancestry of various ethnic groups, including Tibetans, Palestinians, Jews, Ethiopians, Chinese, Brazilians, Aboriginal Australian and various European founder populations.9 When combined with more traditional anthropological tools, genetic testing can help anthropologists reconstruct ancient and recent migrations and familial relationships. However, when these tests are used to determine individual ancestry and heritage the results may be less reliable. By their nature, such tests rely on the accu- racy and comprehensiveness of DNA databanks against which scientists can compare their results. And because the process is intended to involve comparison of frequencies among groups, individual results may differ remarkably from those of the group viewed as a whole. Given that these genetic tests deal with the heritage of individuals and groups, they may well impact on how those individuals and groups see themselves. Humans are very interested in ancestry and any new way of tracing that ancestry is likely to have a wide appeal. However, analysing the results of DNA tests, par- ticularly on individuals, is difﬁcult and open to misinterpretation. There is, for example, no such thing as a Jewish gene, or a Viking gene, or an African gene. Therefore, the possible impact of genetic ancestry tests on individual and group identity is a factor that must be taken into account before, during, and after such tests are carried out. In this regard, a careful reading of the fol-

9 Y. Qian, B. Qian, B. Su, J. Yu, Y. Ke, Z. Chu, L. Shi, D. Lu, J. Chu & L. Jin. Multiple Origins of Tibetan Y-Chromosomes. Human Genetics 2000; 106: 453–454. M.G. Thomas, K. Skoreckiad, H. Ben-Amid, T. Parfitt, N. Bradman & D.B. Goldstein. A Genetic Date for the Origin of Old Testament Priests. Nature 1998; 394: 138–140. G. Passarino, O. Semino, L. Quintana-Murci, L. Excoffier, M. Hammer & A.S. Santachiara-Benerecetti. Different Genetic Components in the Ethiopian Population, Identified by mtDNA and Y-Chromosome Polymor- phisms. American Journal of Human Genetics 1998; 62: 420–434. J.Y. Chu et al. Genetic Relationship of Populations in China. PNAS 1998; 95: 11763–11768. D.R. Carvalho-Silva et al. The Phylogeography of Brazilian Y-Chromosome Lineages. American Journal of Human Genetics 2000; 68: 281–286. A.J. Redd & M. Stoneking. Peopling of Sahul: mtDNA Variation in Aboriginal Australians and Papua New Guinean Populations. American Journal of Human Genetics 1999; 65: 808–828. M. Richards, V. Macauley, E. Hickey, E. Vega, B. Sykes, V. Guida, C. Engo, D. Sellitto, F. Cruciani, T. Kivisild, R. Villems, M. Thomas, S. Rychkov, O. Rychkov, Y. Rychkov, M. Golge, D. Dimitrov, E. Hill, D. Bradley, V. Romano, F. Cali, G. Vona, A. Demaine, S. Papiha, C. Triantaphyllidis, G. Stefanescu, J. Hatina, M. Belledi, A. DiRienzo, A. Novelletto, A. Oppenheim, S. Norby, N. Al-Zaheri, S. Santachiara-Benerecetti, R. Scozari, A. Torroni & H.J. Bandelt. Tracing European Founder Lineages in the Near Eastern mtDNA Pool. American Journal of Human Genetics 2000; 67: 1251–1276.

Josephine Johnston The Hastings Center 21 Malcolm Gordon Road Garrison, New York 10524 USA [email protected]

Mark Thomas The Centre for Genetic Anthropology Department of Biology Darwin Building University College London Gower Street London WC1E 6BT UK [email protected]