Genetic Variation and Human Evolution
Lynn B. Jorde, Ph.D.
Department of Human Genetics
University of Utah School of Medicine.
The past two decades have witnessed an explosion of human genetic data. Innumerable
DNA sequences and genotypes have been generated, and they have led to significant
biomedical advances. In addition, these data have greatly increased our understanding of
patterns of genetic diversity among individuals and populations. The purpose of this brief
review is to show how our knowledge of genetic variation can contribute to an
understanding of our similarities and differences, our origins, and our evolutionary
history.
Patterns of genetic diversity inform us about population history because each major
demographic event leaves an imprint on a population's collective genomic diversity. A
reduction in population size reduces genetic diversity, and an increase in population size
eventually increases diversity. The exchange of migrants between populations inevitably
results in greater genetic similarity, while isolation preserves genetic uniqueness. These
demographic signatures are passed from generation to generation, such that the
genomes of modern individuals reflect their demographic history. Thus, it is reasonable to
say that our history is written in our DNA. As we accumulate more and more data on DNA
variation, and as we develop better tools to analyze these data, our history will become
increasingly clear.
How diverse are we?
Perhaps the most widely cited statistic about human genetic diversity is that any two
humans differ, on average, at about 1 in 1,000 DNA base pairs (0.1%). Human genetic
diversity is substantially lower than that of many other species, including our nearest
evolutionary relative, the chimpanzee. Genetic diversity is a function of a population's
"age" (i.e., the amount of time during which mutations accumulate to generate diversity)
and its size. Our genetic homogeneity implies that anatomically modern humans arose
relatively recently (perhaps 200,000 years ago) and that our population size was quite
small at one time (perhaps 10,000 breeding individuals).
To put the 0.1% genetic diversity estimate into perspective, it is useful to remember that
humans have approximately 3 billion base pairs in a haploid cell. Thus, any pair of
humans differs by approximately 3 million base pairs. These differences contain much
useful information about the evolutionary history of our species. In addition, the small
proportion of differences that occur within genes can lead to critical inferences about the
effects of natural selection.
How is genetic diversity distributed within and between populations?
Human populations can be defined along geographic, political, linguistic, religious, or
ethnic boundaries. Using a common definition that groups populations into major
continents (Africa, Asia, Europe, and North and South America), many studies have
shown that approximately 90% of genetic variation can be found within these
populations, and only about 10% of genetic variation separates the populations. Thus,
the great majority of genetic differences can be found between individuals from any one
of the major continents, and, on average, only a small proportion of additional differences
will be found between individuals from two different continents. Furthermore, because
human history is a history of population movement, and because humans are
extraordinarily adept at sharing their DNA, the genetic boundaries between populations
are typically indistinct. For any given DNA sequence or gene, two individuals from
different populations are sometimes more similar to one another than are two individuals