Why study human evolutionary genetics

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Chapter 1

• Why study human evolutionary genetics?

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Records of the past

• We are all fascinated with our past
• There are many records of the past we can use to
  study our history.
• Historical records
• Linguistics
• Archaeological records
• Paleontological records
• Paleoclimatology records
• Genetics records

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Each record has a certain depth
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Palimpset metaphor

• In the past when materials to note events were in
  short supply people would often write over
  existing texts.
• These overwritten texts are known as palimpsets
• Think of palimpsets in very different ways

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Historical Records

• Historical - written texts - oldest from
  Mesopotamia 4000 years ago
• Cuneiform (wedge shaped), symbols in clay
  tablets, later on papyrus
• Oral histories - harder to check factually

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Languages

• Trace ancestry of all languages (6500) back to a
  common ancestral source.
• All human languages cannot be traced back to a
  common source
• Lots of disagreement due to issues of convergence

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Archaeological records

• Physical objects or artifacts shaped or made by
  humans 2.5mya
• Stone tools, ornaments, pottery, paintings
• Middens (refuse piles), houses, landscapes
• Humans do not appear to be the only animals to
  have made tools- chimpanzees are known to flake
  rocks!

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Paleontological record

• Fossilized or non fossilized remains of living
  organisms.
• Trace fossils- indicate the presence of an
  organisms, i.e. footprint, feces,

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Paleoclimatological records

• Info on past climates aims to reconstruct
  paleoenvironments 100KYA
• Measured via radioisotopes from ice cores from
  ice sheets in Greenland, lake sediments,
  permafrost
• Recreat the biotic environment that once existed
• Geological records

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Genetic records

• Records contained within the genomes of living
  organisms today (and some extinct ones as well).
• Their inter/intra relationships can provide
  detailed info on evolutionary processes and
  relationships back to common ancestors.
• Genomes of living individuals have been passed
  down from ancestors.
• Ancient DNA from well preserved organic remains
  which may or may not have been passed down to
  living descendants.

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Genetic palimpset

• Genetic strata of the past is accessible in the
  analysis of the diversity we find in the genomes
  of humans today. We can use this to determine
• Our relationship to other species
• The origin of our species
• Prehistorical migrations
• Genealogical studies
• Paternity
• Individual identification

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Combining of records

• No single record yields all answers to the past
  so we must combine all records to come up with
  the most parsimonious answer.
• They need not tell us always the same thing

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Reconstructing Genealogy

• The number of ancestors in previous generations
  2t
• t number of generations
• Reality in the past there is some overlap
• 50 generations ago (1250 years 50 x 25 average
  life span)
• 250 1.1315 !!!!
• A weee to many ancestors in the past
• Over 200x the actual amount of people on earth.

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Gene genealogies
present
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Fallacy of contemporary ancestor

• Despite our thirst for understanding who our
  ancestors were we cannot adopt unreliable sources
  of information
• All living organisms share a common ancestor some
  time in the past.
• False statements
• Living fossils
• Humans evolved from chimpanzees
• Modern hunter-gatherers resemble humans before
  agriculture.
• Humans have NOT transcended the rest of the
  natural world! We are not MORE evolved than other
  living organisms!

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Human Chimp Mouse Fish Worm
Fly Yeast E.col
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Importance of shared Evolutionary history

• Nothing in biology makes sense except in the
  light of evolution Dobzansky.
• All our genes and all effects that they control
  have been shaped by the environmental challenges
  our ancestors faced over the last several
  millenia.
• Mouse genes that are identical to human genes
  must have been conserved over evolution for a
  purpose- so organisms such as mice, nematodes,
  zebrafish- can serve as a great model to
  understanding our history

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Structure of DNA the genome
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Chromosomes

• Telomere and centromere heavily repetitive DNA
  sequences
• Heterochromatin
• Stained at high A-T sequences (low GC) low gene
  content
• G banding
• Euchromatin- non repetitive DNA

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G-banding Low GC content
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Genes

• Sections of DNA that code for proteins
• Typically labelled single copy (paternal)
• Between 20,000 and 40,000 genes in our genome
• Expression of genes is more important than the
  code of the genes themselves.

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Functional genes, promoters, gene regulators
Phenotype, selection, regulation (expression)
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Birth of a new Gene?

• Two mechanisms
• Gene duplication
• Exon Shuffling

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• Non-coding DNA
• 98 of our genes do not code for specific gene
  products.
• 70 of our DNA is not even transcribed into RNA!

Non-coding DNA!
Population genetics, diversity estimates,
extinction
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Expression
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Repetitive DNA

• 45 of genome contains repetitive DNA sequences
• What a waste? Why ?
• Amplified things and then not removed from the
  genome- if they are not deleterious they will
  remain in our genome.
• L1
• Alu elements

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Repetitive DNA

• Microsatellites (Short Tandem Repeats) are short
  repeats of simple sequence (150bp) (interspersed
  througout the genome)
• Minisatellites repeats in size 0.1-20kb in length
  (found at chromosomal termini)
• Alu repeat most abundant sequence in the human
  genome about 750K copies ca. 300bp in length
  (interspersed througout the genome).

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Mitosis

• Mitosis- cell division in somatic cells and early
  stages of gametogenesis - post fertilization 1017
  mitotic divisions-lots of replication of DNA-
  room for mistakes!
• 2n cell - 2n daughter cells
• For all somatic cells which undergo duplication
• Results in an exact copy of DNA from previous
  cell
• Fundamentally different than gamete formation

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Meiosis

• Meiosis- 2n -gt 1n cell- halving the number of
  chromosomes- why?
• Gamete cell production - Eggs and Sperm
• 2 main differences between Mitosis and Meiosis
• Meiosis has 2 cell divisions not 1 like mitosis
• Mitosis produces identical cells to parent-
  Meiosis produces cells that are genetically
  different.

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Meiosis

• Differences between gametes happens via 2
  mechanisms
• Independent assortment-random shuffling of
  chromosomes into gametes 223
• Recombination between homologous chromosomes

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Independent assortment
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Recombination

• Recombination - allows us to produce a physical
  map of the chromosomes, or the distance between
  genes.
• Distance expressed as centiMorgans (cM)
• 1 cM 1 recombination frequency between the
  markers (genes)
• 1cM/Mb (Megabase- 1 Million base pairs)
• Recombination is not equal across chromosomes- up
  to 1000x differences!
• Hot spots and cold spots!

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Recombination

• Females have 80 recombination events making eggs
• Males have 50 recombination events
• Genetic map in females is 1.65 fold expanded
• Recombination is more frequent at the Telomeres
  (3cM/Mb) less so at the centromeres (1cm/Mb)
• 2x the rate on small chromosomes than larger ones

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Rate increase
Rate increase
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Non recombining sections

• Mitochondrial DNA is non-recombining
• Y-chromosome (most of it)

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Origins of mtDNA

• Endosymbiotic bacteria engulfed a proto
  eukaryotic cell 1.5 billion yrs ago.
• Circular genome not linear
• No histones
• Discrete origins of replication
• No introns, repeats
• 2 promoters one on each strand
• Different genetic code