Human Sciences Final Honour School: Paper 2
HUMAN GENETICS AND EVOLUTION
Human Population Genetics
Tutorial 1 – Genetic diversity in human and chimpanzee populations
The purpose of this tutorial is to look at laboratory, statistical and population genetic methods
used for measuring and studying genetic diversity within human and chimpanzee populations.
Until about 15 years ago, the most widely used methods for surveying diversity characterised
the protein products of genes, such as blood groups (serology) and enzymes (electrophoresis).
However, even back in the eighties, many geneticists began using DNA polymorphisms, in
particular restriction fragment length polymorphisms (RFLPs), and their linkage patterns:
haplotypes. Microsatellites and other VNTRs (variable numbers of tandem repeats) in the
nuclear genome became popular in the nineties, as did mitochondrial (mt)DNA. Now,
sequencing of DNA in the nuclear genome has become routine, but is still sufficiently timeconsuming and expensive that many studies of population diversity target known SNPs (single
nucleotide polymorphisms) for genotyping instead of sequencing a full gene sequence again
and again for large numbers of individuals.
The magnitude of genetic diversity is indicated by the number and range of allelic types
observed at polymorphic loci among individuals sampled from a population. Heterozygosity is
the average diversity observed in pairs of chromosomes, for example within diploid
individuals.
Two different statistical approaches for studying the distribution of diversity within and
between human populations have been popular. One approach is to measure the apportionment
of genetic variances within and among populations, eg using Wright’s F statistics (Hartl and
Clark, 1997, 3rd ed. P. 117-122). A second approach is to measure genetic distances, and from
matrices of genetic distances, construct trees, or phenograms, to represent phylogenetic
relationships between populations (Cavalli-Sforza, 1998). Both of these approaches can be
applied to protein and DNA polymorphisms.
Diversity data measured at the DNA level are particularly valuable for application of simple
population genetic models. Under neutrality, higher mutation rates and/or larger population
sizes are expected to generate higher genetic diversity. Put the other way round, diversity data
can be used to estimate a simple parameter of population genetic models called which is
proportional to the product of the mutation rate and population size.
Much more is known about diversity in humans than in chimps, but some studies of how
diversity is distributed between chimp populations, subspecies and species, have now been
done. Do humans and chimps have comparable levels of total diversity? How is the total
diversity within the species distributed among populations? Compare different statistical
methods for analyzing levels of diversity and for describing relationships between populations.
Do the polymorphisms in different loci, eg mtDNA, Y chromosomes or nuclear genes, reveal
the same levels of diversity or the same patterns of distribution within and among populations?
Essay Topic: ‘Humans have low genetic diversity compared with chimpanzees’. Discuss
the evidence for this statement and its implications.
General reading:
Hartl, D.L. and Clark, A.G. (1997) Principles of Population Genetics. Sinauer. (Chapter 1:
Genetic and statistical background; Chapter 2: Genetic and phenotypic variation;
Chapter 4: Population substructure).
Jobling, M.A., Hurles, M.E., and Tyler-Smith, C. (2004) Human Evolutionary Genetics:
Origins, Peoples and Disease. Garland Publishing, New York. Chapter 7.
Diamond, J. (1991) The Rise and Fall of the Third Chimpanzee. Radius. Chapter 1.
Hey, J. and Machado C.A. (2003) The study of structured populations – new hope for a
difficult and divided science. Nature Reviews Genetics 4 (July): 535-543.
Pääbo, S. (2003) The mosaic that is our genome. Nature (23 January) 421:409-412.
Relethford, J.H. (2003) Reflections of Our Past. Westview Press, Colorado, USA. Chapter 5
Scheffrahn, W., Brandt-Casadeval, C., and Kratzer, A. (2002) Human Population Genetics in a
Primatological Context. Evolutionary Anthropology, Suppl 1:171-174
The following essays are from the Encyclopedia of Life Science, http://www.els.net/
Harrison, R.M. (2001) Variation, Within Species: Introduction. ELS
Takahata N. (2001) Molecular Evolution: Neutral Theory. ELS
Wade, M.J. (2002) Population Structure. ELS
Variation within and between human populations:
Lewontin, R.C. (1972) The apportionment of human diversity. Evolutionary Biology
6:381-398.
Barbujani, G., Magagni, A., Minch, E. and Cavalli-Sforza, L.L. (1997) An apportionment of
human DNA diversity. Proceedings of the National Academy of Sciences, USA
94:4516-4519.
Brown, R.A. and Armelagos G.J. (2001) Apportionment of racial diversity: a review.
Evolutionary Anthropology 10:34-40.
Human diversity at the DNA level:
Kaessmann, H., Heiig F, von Haeseler A. and Pääbo, S. (1999) DNA sequence variation in a
non-coding region of low recombination on the human X chromosome. Nature
Genetics 22:78-81.
Li, W.-H. and Sadler, L.A. (1991) Low nucleotide diversity in man. Genetics 129:513-523.
Przeworski, M., Hudson, R.R. and Di Rienzo, A. (2000) Adjusting the focus on human
variation. Trends in Genetics 16(7): 296-302.
Yu, N., Zhao, Z., Fu Y.-X., Sambuughin, N., Ramsay, M., Jenkins, T., Leskinen, E., Patthy, L.,
Jorde, L.B., Kuromori T., and Li, W.-H. (2001) Global patterns of human DNA
sequence variation in a 10-kb region on Chromosome 1. Molecular Biology and
Evolution 18(2):214-222
Yu, N., Chen, F.-C., Ota, S., Jorde, L.B., Pamilo, P., Patthy, L., Ramsay, M., Jenkins, T.,
Shyue, S.-K., and Li, W.-H. (2002) Larger genetic differences within Africans than
between Africans and Eurasians. Genetics 161:269-274.
Chimp diversity studies:
Kaessmann, H., Wiebe, V. and Pääbo, S. (1999) Extensive sequence diversity among
chimpanzees. Science 286:1159-1162.
Gagneux, P. et al. (1999) Mitochondrial sequences show diverse evolutionary histories of
African hominoids. Proceedings of the National Academy of Sciences, USA 96:50775082.
Gagneux P. (2002) The genus Pan: population genetics of an endangered outgroup. Trends in
Genetics 18(7): 327-330
Morin, P.A., Moore, J.J., Chakraborty, R., Jin, L., Goodall, J. and Woodruff, D.S. (1994) Kin
selection, social structure, gene flow, and the evolution of chimpanzees. Science
265:1193-1201
Human-Chimpanzee differences:
Cyranoski D. (2002) Chimpanzee genome: Almost human… Nature 418:910-912.
Deeb, S. S., Jorgensen, A. L., Battisti, L., Iwasaki, L., and Motulsky, A. G. (1994) Sequence
divergence of the red and green visual pigments in great apes and humans. Proceedings
of the National Academy of Sciences, USA 91:7262-7266.
Gagneux, P. and Varki, A. (2001) Genetic differences between Humans and Great Apes.
Molecular Phylogenetics and Evolution 18(1):2-13
Gu, J. and Gu, X. (2003) Induced gene expression in human brain after the split from
chimpanzee. Trends in Genetics 19(2):63-65
Hacia, JG (2001) Genome of the apes. Trends in Genetics 17(11):637-645.
Kaessmann, H. and Pääbo, S. (2002) The genetical history of humans and great apes. Journal
of Internal Medicine 251:1-18
Olson, M.V. and Varki A. (2002) Sequencing the chimpanzee genome: insights into human
evolution and disease. Nature Reviews Genetics (Jan) 4:20-28.
Wildman, D. E., Uddin, M., Liu, G., Grossman, L. I., and Goodman, M. (2003) Implications of
natural selection in shaping 99.4% nonsynonymous DNA identity between humans and
chimpanzees: Enlarging genus Homo. Proceedings of the National Academy of
Sciences, USA 100:7181-7188.