Exam and ''

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Exam and ..

• 20 questions 5 pts each
• You must answer 18 of those 20!
• You have 3 hours
• Everything since lecture 6 (including lecture 6)
• Today- you have to do my evaluations as well as
  my TAs evaluations.. Sorry about that! - )
• Read Chapter 14 know single vs complex diseases
• Office hours today at 1240-2pm

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Human variation and phenotype

• Underlying mechanisms
• Acclimatization - rapid reversible responses to
  environmental change.
• Tanning
• Developmental plasticity- environment influences
  the long-term development of an individual.
• poor nutrion to metabolism
• Adaptation to high altitude (oxygen acceptance)
• Must contain some genetic influences
• Direct responses- genetic changes which are
  directly responsible for underlying phenotypic
  variation.

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How do you uncover the culprit gene(s)?

• Teasing apart innate (genetic) basis for a
  characteristic vs. environmental basis is not
  easy
• Quantitative genetics- The study of Quantitative
  Trait Loci (QTLs) contributing to complex traits.
  It aims to decompose the total variance in a
  phenotype into various genetic and environmental
  components.
• One way would be to study twins- but this is not
  easy to completely control the environment- nor
  is it ethical to do so.
• Candidate gene approach- look for a gene which
  controls an effect (obesity, diabetes etc)

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Evolutionary genetics of pigmentation

• Skin color shows a highly non-random geographical
  distribution.
• Darkest skin in the tropics of Africa, lighter
  skin in the northern regions.
• If we think of it as a QTL the proportion of
  variation between populations is really high
• Fst 0.6 as opposed to 0.15 for neutral autosomal
  markers.
• Why such a high FST between populations?

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Evolutionary genetics of pigmentation

• Melanin - granular substance produced by
  specialized cells called melanocytes that lie at
  the boundary between the dermis and epidermis.
• Is important not only in the color of the skin
  but the color of hair and eyes.
• Melanin is concentrated in vesicles known as
  melanosomes and these are transported into
  keratinocytes.
• The number of melanocytes is similar between most
  people however the variation in skin color
  results from differences in the number and
  distribution of the melanosomes within the
  keratinocytes.
• Dark skin contains many large dark melanomsomes
  and lighter skin contains smaller and less dense
  melanosomes

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Evolutionary history of pigmentation

• What was the skin color on the ancestor of human
  and chimps?
• Likely light skin with hair
• Surprising but most primates have white skin
  protected by hair.
• It is believed that the onset of bipedalism
  required the cooling of our core temperature and
  this thus required loss of hair to keep our
  bigger brains cooler.
• Loss of hair and increase in sweat glands

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Evolutionary history of pigmentation

• Bare skin is sensitive to UV radiation, mostly in
  the form of UV-B.
• To protect the skin from UV-B skin melanization
  was strongly favored or selected for especially
  in environments in higher UV radiation
  environments.
• The most recent ancestor of modern humans is
  presumed to have had dark skin color.
• Thus to explain the variation across the globe
  today we must think in terms of loss of
  pigmentation as we move away from Africa.

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Melanins protective role

• Protection is 2 fold.
• Reduces the amount of radiation entering the
  deeper tissues by absorbing/scattering it
• Filters the byproducts of UVR damage such as free
  radicals.
• What were the selective pressures imposed by UVR?
• Short term UVR causes sunburn- this can lead to
  damage of sweat glands and overheating- light
  skin would have been selected against
• Long term UVR- causes cancer degenerative changes
  in the dermis while significant- they likely
  occur post reproductive age and thus would not
  have been selected for.
• UVR causes nutrient photodegradation in the skin-
  Many important nutrients such as carotenoids,
  flavins are sensitive to photo degradation.
  Folate- which is important for DNA metabolism,
  degrades in UVR conditions thus darker skin would
  be more favored.

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Melanins protective role

• What were the selective pressures imposed by UVR?
• Short term UVR causes sunburn- this can lead to
  damage of sweat glands and overheating- light
  skin would have been selected against
• Long term UVR- causes cancer degenerative changes
  in the dermis while significant- they likely
  occur post reproductive age and thus would not
  have been selected for.
• UVR causes nutrient photodegradation in the skin-
  Many important nutrients such as carotenoids,
  flavins are sensitive to photo degradation.
  Folate- which is important for DNA metabolism,
  degrades in UVR conditions thus darker skin would
  be more favored.
• UVR and Vitamin D synthesis- UVR plays an
  important role in the production of Vitamin D. D
  is involved in mineralization and growth of
  normal bone during infancy and childhood. Most
  vitamin D comes from UVR rather than dietary
  substances. Improper amounts of vitamin D can
  lead to skeletal irregularities in the pelvic
  region and thus poor health of newborns.

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Equator
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Genes in human pigmentation

• 100 genes identified in coat color control in
  mice
• 40 of these have been cloned- many have human
  phenotypes.
• Main pigmentation genes are MC1R mutations in
  this gene affect not only human pigmentation but
  also that of wild animals, mice and many
  domesticated animals.
• The gene is highly polymorphic with over 30
  alleles- three of which have been shown to be
  associated with red hair, fair skin and
  freckling.

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Geographic variation

• If selection has been acting on human
  pigmentation genes, then the signals of that
  selection should be apparent in patterns of
  haplotype diversity.
• 1 gene studied to date MC1R.
• This gene reveals a striking difference in the
  distribution of haplotypes between African and
  Eurasian populations.
• 5 haplotypes in Africa and NO amino acid
  substituions and Eurasia has 13 haplotypes with
  10 aa subs!!!

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Geographic variation

• If human consensus is compared with chimpanzee
  consensus they are very similar at the aa level.
• Very similar Amino Acid sequence between African
  and chimp sequences due to functional constraint
  on the protein.
• Selection to maintain dark skin in African
  populations

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