Human Evolution Adaptive Evolution through Selective Sweeps Evolution of the Human Lifespan

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Human EvolutionAdaptive Evolution through
Selective SweepsEvolution of the Human Lifespan

• Presented by
• Heidi Carpenter, Melissa Pfeffer, Sarah Winks,
  Wen-Ching Lien, and Hannah Pealstrom

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Localizing Recent Adaptive Evolution in the
Human GenomeScott H. Williamson, Melissa J.
Hubisz, Andrew G. Clark, Bret A Payseur,
Carlos D Bustamante, Rasmus Nielsen

• Genomics has made it possible to look at how
  adaptation affects genetic variation
• nonsynonymous vs. synonymous mutations
• Weak negative selection against harmful mutations

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How does adaptive evolution affect DNA sequence
polymorphisms and what types of selection have
occurred?
http//upload.wikimedia.org/wikipedia/commons/thum
b/2/2e/Dna-SNP.svg/220px-Dna-SNP.svg.png
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• Recent evolution in humans
• Identify genomic locations for Selective Sweeps
  (also hitchhikers)

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• Molecular signature of a sweep

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• Location of adaptive events functional
  knowledge of genomic region
• knowledge of recent human evolution
• Important in understanding
• inherited diseases and
• infectious disease resistance

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• 1.2 million human single-nucleotide polymorphisms
  as their data
• Chinese
• European-American
• African-American
• CLR method

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Why Men Matter Mating Patterns Drive Evolution
of Human LifespanShripad D. Tuljapurkar, Cedric
O. Puleston, Michael D. Gurven

• Evolutionary theory - as we age and no longer
  reproduce, selection against harmful mutations
  weakens
• Women stop reproducing and reach menopause by age
  55, mutations should accumulate and lead to
  mortality

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• Wall of Death W. Hamilton
• In hunter-gatherer populations, 31 of people
  live past 55yrs
• In industrialized populations, life expectancy is
  75 85 yrs.

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• Ecological explanations for lifespan beyond
  female menopause
• Grandmother Hypothesis
• enhanced fitness and
• survival of young and others
• through care given by older
• women in the population.

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• This paper uses a two-sex model, because we have
  to consider that males can reproduce at high ages
  past female menopause
• Male mating patterns allow humans to avoid Wall
  of Death
• Age gaps in marriage i.e. older men younger
  women
• Serial monogamy
• Polygyny
• Gerontocracy

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• Overcome Haldanes rule problematic to be the
  heterogametic sex
• Men and their mating preferences
• are important in human evolution
• because they help increase longevity
• in the human lifespan.

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Results

• Localizing Recent Adaptive Evolution in the Human
  Genome
• Scott H. Williamson, Melissa J. Hubisz, Andrew G.
  Clark, Bret A. Payseur, Carlos D. Bustamante,
  Rasmus Nielsen

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Pigmentation

• Darkens with increasing UV intensity
  (protective),lighter skin able to produce more
  vit. D.
• Explanation of some inconsistencies (i.e.
  inuit/chukchi and nordic peoples) high seafood
  meat diet vs not.
• Evidence for recent selective sweeps in Chinese
  and Euro-american populations, some evidence of
  partial selective sweeps in african-american
  population. KITLG in particular signaling
  molecule, stimulates melanocyte proliferation,
  growth and dendricity.

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Table 2
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Heat shock proteins

• Involved in the folding/unfolding of other
  proteins
• Expression is increased cells are exposed to
  elevated temps, stress conditions (inc. immune
  assalts)
• Chinese population showed evidence of approx. 20
  selective sweeps, euro-american 14 selective
  sweeps, african american 1 selective sweep.

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Nervous system dev. and fxn.

• DAB1 (Disabled-1) gene codes for an adapter
  protein a regulator of Reelin signaling. Reelin
  controls cell positioning in the developing brain
  adult neurogenesis. In humans, Reelin mutations
  are associated with brain malformations and
  mental retardation. In mice, Dab1 mutation
  results in the scrambler mouse phenotype.
• New version of DAB1 gene shown to be universal
  among those of chinese ancestry, not found in
  other global pops.
• SV2B gene ecodes a synaptic vesicle protein with
  highest expression during brain development,
  strong evidence for selective sweep in the
  african american sample.

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Olfactory receptors

• Humans have approximately 400 functional types of
  olfactory receptor, but have about 1000 genes
  coding for olfactory receptors.
• Approximately 600 are pseudogenes or junk DNA.
• The olfactory receptor gene family in vertebrates
  has been shown to evolve by birth-and-death
  evolution, whereby new genes within the family
  are created through genomic events such as gene
  duplications or gene conversions.
• Evidence for olfactory receptor sweep observed
  mainly in the african-american sample.

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Dystrophin protein complex

• The genomic region with the strongest evidence of
  a recent selective sweep is the DTNA gene.
• DTNA encodes the dystrobrevin protein, a
  component of the dystrophin protein complex
  (DPC).
• Aside from DTNA, several other genes that
  contribute to the DPC show evidence for recent
  selective sweeps , including several syntrophin
  and sarcoglycan genes.
• The DPC primarily fuctions as a key structural
  component in the architecture of muscle tissue.
• Dystrophin and dystrophin associated proteins
  are associated with muscular dystrophy.
• There are different types of muscular dystrophy
  but the common types are X-linked ( Duchenne,
  Beckers)
• Duchenne 1 in 3500 males Beckers 1 in 30000
  males
• DMD under represented in black african population

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Immune system

• Cluster of differentiation 226 (CD226) gene
  codes for a trans-membrane protein involved in
  the cytotoxicity of natural killer cells and T
  cells
• IGJ gene codes for a Immunoglobulin J chain, a
  protein (an immunoglobulin) responsible for
  linking other immunoglobulins to each other.
• Thymic stromal lymphopoietin (TSLP) gene codes
  for a protein belonging to the cytokine family.
  It is known to play an important role in the
  maturation of T cell populations through
  activation of antigen presenting cells and
  thought to play a role in B-cell development.
  TSLP expression is linked to many disease states
  including asthma, inflammatory arthritis, atopic
  dermatitis and eczema and other allergic states.
  Autoimmune disorder/diseases and allergies.
• RAG1/RAG2 genes recombination activating genes
  (RAGs), code for enzymes which help generate
  diversity of immunoglobulins and T cells. RAG-1
  and RAG-2 are essential to the generation of
  mature B and T lymphocytes, two cell types that
  are crucial components of the adaptive immune
  system.
• Chinese population showed the most strong
  selective sweeps, european american showed fewer
  strong selective sweeps, african american
  population showed none.

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Figure 1
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CLR approach and p values

• CLR composite likelihood ratio
• Test gives a p value
• a .05
• To be statistically different p lt .05

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Centromeric Regions

• Show extreme spatial patterns
• Chromosome 16 has large affected area
• Evidence for selective sweeps on 8 chromosomes
• Suggests functional genomic elements targeted by
  selection
• European-American and Chinese very low p value
  in CLR test

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e-function-definition.html
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Recombination Hotspots

• Most recombination event occur in hotspots
• 5kb fragments with avg. distance of 50 kb between
• Recombination rate assumed to be 8-fold higher
  than background
• Calculated p values under constant recombination
  and recombination hotspots

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Recombination Model

• Figure 3. A Comparison of p Values of the CLR
  Test, Calculated from Simulations of Models
  Assuming a Constant Recombination Rate and Models
  That
• Include Recombination Hotspots
• (A) The combined sample.
• (B) The African-American sample.
• (C) The European-American sample.
• (D) The Chinese sample.
• p Values are highly consistent between constant
  recombination and hotspot models, indicating that
  the CLR test is robust to recombination rate
  variation. Note that both axes are on a log scale.

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Demographics Model

• Effects on CLR in
• presence of complex
• population demography
• Test in constant duration and varying severity
• Only testing strength of bottlenecks in
  non-African populations
• Population reductions ranging from 50 - 99

http//en.wikipedia.org/wiki/FilePopulation_bottl
eneck.svg
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Bottleneck Model
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False Discovery Rate (FDR)

• Estimates probability that they can accept the
  null hypothesis in multi-hypotheses testing
• Estimates the number of tests where null
  hypothesis is false
• Looks at the distribution of p values among tests
• Allows to see proportion of genome affected by
  selective sweeps at linked sites

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FDR Results

• Figure 6. The Fraction of Tests for Which the
  Null Hypothesis Is False, Estimated Using a FDR
  Procedure and Shown for Four Alternative
  Evolutionary Models (1) The equilibrium, random
  mating, neutral model. (2) The Marth et al. 25
  bottleneck and growth model. (3) The most
  conservative non-African bottleneck model. (4)
  The complex demographic and recombination model
  calibrated by Schaffner et al. 50.
  doi10.1371/journal.pgen.0030090.g006

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In Conclusion

• More selective sweeps in Chinese and
  European-American population than in the
  African-American population.
• Hypothesis as anatomically modern humans migrate
  out from sub-Saharan Africa, the environment they
  encountered imposed new selective pressure and
  lead to an increased rate of population-specific
  selective sweeps.

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Caveats

• The statistical power to detect selective sweeps
  is likely to be much lower in the
  African-American sample.
• Admixture of African and European lineages in the
  African-American population may weaken the signal
  of Africa-specific selective sweep
• Extensive subdivision among African population.
• Admixture between subpopulations within Africa,
  followed by admixture with European populations.
• Therefore, it is premature to conclude that the
  rate of adaptation has increased in non-African
  population.

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In conclusion (cont.)

• More evidence for selective sweeps within
  subpopulation compared to the cosmopolitan
  sample.
• Suggest that adaptation to local environments has
  been an important force in recent human evolution
• However, more evidences might due to the power
  to detect is greater in local population

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• Weak negative selection operating on the SNPs
• locally skew allele frequencies
• could mimic a selective sweep.
• but the localized weak selection does not have a
  systematic effect on the result
• Vast majority of SNPs are with no known function
• sweep they detect is population-specific.
• Greater evidence for selective sweeps in
  non-African population.

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It is complementary to previous divergence-based
approaches
Divergence-based approach Present approach
detect adaptive changes that have occurred via recurrent amino acid substitutions within a gene detect adaptive changes at all functional genomic categories.
Detect molecular adaption that has occurred at any time on the lineage separating human and chimps. detect ongoing or very recent selection(lt200,000yrs)
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More Advantages

• More powerful to investigate the adaptation of
  subpopulations to local environments at the
  molecular level.
• Fills some of the gapes in the knowledge of human
  adaption evolution.

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Further Studies

• identify the traits that have been affected by
  recent adaptation and the selective forces that
  have shapes human population.

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DiscussionWhat reasons do you think centromeric
regions would be targeted for selection? What
functional elements may they serve as?
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• Given that Muscular Dystrohpy is reported to be
  underrepresented in black African populations vs.
  all other populations, what explains this
  finding?

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• Since this paper looked at the genome from
  European-Americans instead of Europeans, and
  assuming there has been mixture of genomes within
  America, do you think there would be more or less
  evidence of selective sweeps in European
  populations compared to Chinese population
  samples?

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Why Men Matter Mating Patterns Drive Evolution
of Human Lifespan

• Shripad D. Tuljapurkar, Cedric O. Puleston,
  Michael D. Gurven

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What We Should SeeOne-Sex Female Demography

• Weakened selection with increased age
• -Increased frequency of deleterious alleles (on
  autosomal chromosomes) as selection declines with
  age
• Accumulation of mutations
• -Reduces survival at old age leading to rise in
  mortality as female reaches menopause (Age
  Specific Mortality)
• -Evolutionary Theory of selection against rare
  mutation (that reduces survival at any age) is
  proportional to female expected survival-weighted
  reproduction past specific age

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Wall of Death
S(x) Selection by age
S(0) Selection at birth
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But We DontPossible Explanations

• Ecological
• -Value transfers
• - Grandmother Advantage
• -Economic Efficiency
• not framed to track gene frequency
• OR
• Male Reproduction Mating Patterns
• -Remember reproductive potential is due to all
  reproducing individuals, whereas reproductive
  fitness is derived solely from females
• http//assets.flavorwire.com/wp-content/uploads/20
  10/08/BettyWhite-TM.jpg

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Who/What They Looked at
WomenDashed Red Men Solid Blue
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Results/Methods

• Rare autosomal mutation affecting mortality past
  age 55 of female menopause
• -Affects survival rate of both sexes at age J
  (male age)gtK (age of menopause) past last female
  reproduction
• Initial rate of increase of rare mutant allele is
  due to strength of selection
• -Female- Only Model post menopausal mutation
  does not effect population growth (Strength of
  Selection0)
• -Male- Only Model selection independent of
  mating patterns/female population
• Depends on male-to-female age-sex composition
  mating rules
• -Positive marginal fertility in males as long
  as male fertility is nonzero

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Results/Methods cont.

• Strength of selection is proportional to expected
  reproduction by males older than age K (female
  menopause)
• As long as males have fertility not equal to
  zero, and are reproducing AFTER age Jgt0
• There is selection against deleterious mutations
  acting after female menopause
• Slt0 because of older male-younger female mating
• Selection pressure persists to later age for both
  men and women

BlueTwo-sex model
Redfemale-only model
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Male Fertility Distribution

• Including male fertility effects
• shape of wall of death curvature
• Long tail w/ continued late-age fertility slows
  increase in mortality
• Comparative fertility distribution

France
Pakistan
Cameroon
Male fertility in1980 France (black), Pakistan
1984 (blue dots) and Cameroon 1964 (red dashes).
Redrawn from Paget and Timaeus 24 Cameroon's
distribution is common of high-fertility
polygynous societies. The Y-axis shows
age-specific fertility rates as a fraction of the
total fertility rate.
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Discussion

• Survival-Weighted reproduction in a sex- related
  model is related to age-specific force of
  selection
• Supply of older males in early human evolution
  influenced natural selection early humans may
  have had smaller proportion of younger males
• Some genes have beneficiality both pre- and post-
  reproduction age selection against damaging
  mutations
• Male Female Model shows selective action
  against mutations reducing survival which in turn
  delays onset of rapid senescence in both sexes

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Questions?
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Citations for Pictures

• Opening Slide
• http//www.google.com/search?qgeorgeclooneyhle
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  bih812
• http//www.biol.wwu.edu/biology/faculty.shtmlp
• http//mayasim.uoregon.edu/images/rtphoto/cpulesto
  n.jpg
• http//news.stanford.edu/news/2007/september12/gif
  s/man_tulja.jpgw300h412eiADJZT_ywJ4aMigL80sW
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  97page1tbnh180tbnw156start0ndsp21ved1t
  429,r5,s0tx112ty62
• Cameroon people http//sb.westfordk12.us/pages/6m
  web/6mss/travelpages/2/2Kevin16/images/Cameroonpeo
  ple.jpg
• Slide 6
• http//images.travelpod.com/users/travel_lover87/2
  .1259320390.5_san-bushmen.jpg
• http//www.meatradio.com/uploads/images/header_ima
  ges/Ache_331b.jpg
• http//www.nationalgeographic.com/adventure/0204/i
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  1vpy148dur384hovh180hovw279tx233ty154
  sig113909557034289598792page4tbnh157tbnw210
  start46ndsp16ved1t429,r3,s46
• http//www.psych.ucsb.edu/research/cep/grads/Sell/
  TsimaneSite.html
• http//www.happytellus.com/img/gambia/a-village_58
  64.jpg
• http//therealdeal.com/miami/wp-content/uploads/20
  12/02/canadians.jpg
• Slide 11
• http//sacred-sites.org/wordpress/wp-content/uploa
  ds/2011/07/YanomamiElder.jpg
• http//www.google.com/imgres?um1hlenclientfir
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  http//www.alien-ufos.com/armageddon-end-times/26
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  429,r11,s0

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Debate

• Considering the implications of both Ecological
  and Biological factors on lifespan after female
  menopause, which do you think has a greater
  influence men or ecology?
• hint how might asexual/sexual reproduction and
  sexual selection play a part?

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• Discuss
• What effect do you think a change in male mating
  patterns (i.e. smaller age gap, monogamy) could
  have on life expectancy?

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• As the age of first reproduction steadily
  increases for women present day, what affects on
  senescence and selection might occur?