Human evolutionary history

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Human evolutionary history

• and disease susceptibility

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How could history matter?

• Same genotype in different environment
• Well-adapted / mal-adapted locally in time/space
• Consider recently migrated individuals like
  Afro-Americans
• Recently changed culture like use of grains,
  alcohol, milk, nicotine
• Recently changed pathogen pressure

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How could history matter?

• Different allele frequencies in different
  populations
• Fitness-neutral allele diluted during migration
• Migration distance ? genetic similarity
• Adaptation to local environment
• Isolated populations become different from total
  by drift
• Jews, Gypsies, Urkers
• Old polymorphisms can be common and shared by
  many populations, new polymorphisms can be rare
  and local

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Effect of migration
Directional migration in empty space new
mutations go downstream New mutation in standing
population diffusion
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• Population differences are common
• Genotype-phenotype
• Genotype freq/distribution
• Results differ between populations
• Often more if further apart
• Pooling populations can alter outcome tests
• Be aware when designing/interpreting experiments

Evolutionary knowledge can help understand
prevalence, environmental factors, etc.
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Not all things show gradients
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Patterns of heritable diseases
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• Sickle cell anaemia
• A number of polymorphisms
• cause s.c.a (recessive)
• protect against malaria (dominant)
• s.c.a. common where malaria is/was common

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• Lactose intolerance
• Ancestral trait
• Decreased in pastoral populations
• Different genes in Africa/Europe

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K. Rostami, R. Malekzadeh, B. Shahbazkhani, M. R.
Akbari and C. Catassi, 2004
Gluten intolerance (coeliac disease) Gluten is
present in wheat, rye, spelt, .. but not in corn
or rice HLA-types DQ2 and DQ8 seem necessary for
celiac disease HLA plays a role in immunity
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Genetics and/or culture?
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Blacks in USA suffer more from hypertension than
in Africa Probable explanation Blacks are
adapted to high temperatures, low salt, high body
fluid volume differences ? Mal-adapted in
temperate climate with low sweating and
sufficient salt Multiple polymorphisms involved
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Application of evolutionary knowledge in medical
research
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Some examples

• Gene function from comparison with other species
• Gene (domain, AA) importance from conservation
• Association analysis in isolated populations
• (Association) studies take ethnicity into account