Download 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 distinction 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 archaeological 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 opposition to natural selection to explain why certain genetic traits
change their frequency in a population over time. The theory predicts 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.
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and 350 Main Street, Malden, MA 02148, USA.
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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 Xchromosome 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 Xchromosome 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 Ychromosomes 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, complete with that man’s polymorphisms. As scientists know approximately 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 construct 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
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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 statistics. 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.
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.
6
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SUMMARY: THE SCIENCE OF GENEALOGY BY GENETICS
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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 accuracy 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, particularly 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 fol9
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 Polymorphisms. 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.
© Blackwell Publishing Ltd. 2003
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lowing cases may help illuminate the identity issues that can arise
in genetic ancestry testing.
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]
© Blackwell Publishing Ltd. 2003