Influence of Y Chromosome on Human Evolution

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Influence of Y Chromosome on Human Evolution

• Jordan Miller, Jessica Perry, Eric Porsch, Sean
  Scheler

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Human Evolution

• The application of genetics in the study of human
  evolution has contributed to our understanding of
  
• Population Genetics
• Trace origin and distribution of populations
• Identify individuals that belong to populations
• Origin of Humans
• Hypothesis that all contemporary humans are
  derived from an common ancestor who lived in
  Africa approximately 200,000 years ago

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Polymorphisms

• Polymorphisms are more than one form of a gene
  within a population
• Useful in population genetics
• Numerous and dispersed throughout the genome
• Basis of current genetic markers
• Restriction Fragment Length Polymorphisms (RFLPs)
• Minisatellites
• Microsatellites

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Mitochondrial DNA

• Small circular genome located within the
  mitochondria in the cytoplasm of the cell
• Codes for only 13 polypeptides
• The non-coding region of mtDNA is highly
  polymorphic

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Mitochondrial DNA

• Certain characteristics make it well-suited for
  evolutionary studies
• Strictly maternal mode of inheritance
• mtDNA variation occurs only through mutation
• High copy number
• Rapid rate of evolution
• Useful in evolutionary studies such as
• Reconstructing human origins
• Tracing population history
• Analyzing ancient DNA

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Basic Characteristics of the Y Chromosome

• Represents 2 of the human genome (60 Mb in
  length)
• Non-Recombining portion of the Y-chromosome
  (NRPY)
• Pseudoautosomal Regions
• PAR1 and PAR2
• Short Tandem Repeats (STR)
• Single Nucleotide Polymorphisms (SNP)

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Non-Recombining portion of the Y-chromosome (NRPY)

• These are the regions of the Y Chromosome that
  exclude the pseudoautosomal regions.
• NRPY makes up 95 of the Y chromosome.
• Two types of NRPY
• Non-recombining euchromatic portion of the Y
  Chromosome (NREPY).
• Non-recombining heterochromatic portion of the Y
  Chromosome (NRHPY)
• Preserves the records of mutations that have
  occurred throughout male evolution.
• This is so because the chromosome does not take
  part in recombination (the crossing over event).
• NRPY are similar to the mtDNA which records
  mutation events in females.

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Strachnan Read
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Pseudoautosomal Regions

• Are called pseudoautosomal because there is
  limited exchange of information between the X and
  Y Chromosome.
• These sequences are not X or Y linked.
• Located at the Distal ends of the chromosome.
• PAR1 and PAR2
• Helps in the correct pairing of the sex
  chromosomes in meiosis.
• The X chromosome has these regions as well.

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PAR1 and PAR2

• PAR1
• 2.6 Mb on the short arm, and contains at least 13
  genes.
• Site of obligated crossover during male meiosis
  which is important to correct segregation.
• Contains highly recombinogenic sequences.

• PAR2
• 330 kb on the long arm, only contains 4 genes.
• Obligated crossing over does not occur in the
  PAR2 region as much as the PAR1 region.
• Does not play a role in correct segregation
  unlike PAR1.

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Short Tandem Repeats (STR)

• These are sequences that are located in the NRPY.
• Also called microsatellites
• Are highly polymorphic
• Ranging from 1-6 bp
• Are very specific for particular populations.
• Useful in forensics

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Single Nucleotide Polymorphisms (SNP)

• Most frequent polymorphism found on the Y
  Chromosome.
• Can be analyzed from a low amount of DNA.
• Low mutation rate allows for paternity testing.

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Biological Functions Of theY Chromosome

• Important biological implications for
  male-specific functions
• Male fitness
• Testis determination and Male fertility
• SRY gene (short arm of the Y)
• NRY region

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Genes and mutations on PAR1,2 and NRPY regions

• SHOX (short stature homebox-containing)
• ZFY (zinc finger y)
• DBY (DEAD box, Y)
• SRY (Sex reversal Y)
• CXYorkf1 (CXYorkf1)

• Located on PAR1 (short stature)
• Turner Syndrome?
• Infertility
• Y XX male, 46 XY gonadal dysgenesis
• Unknown function

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Human Evolution and the Y Chromosome

• Always in the haploid state
• Does not undergo recombination during meiosis
• Transmitted intact through paternal lineages
• All of these features make the study of
  Y-chromosome variation extremely useful,
  especially for population histories.

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Haplogroups

• Haplotype A set of closely linked alleles that
  are inherited as a unit.
• Based on sequence variation, different Y
  chromosome haplotypes can be classified into
  haplogroups which usually correspond to each
  continent and major ethnic group.
• Thus, the genetic differences can be used to
  study relatedness of worldwide populations

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Double-Edged Sword

• Can be used successfully in paternal genealogies
• Population substructure may cause problems
• Male-specific migration
• Founder effects
• Genetic drift
• These can lead to over-representation of
  haplotypes in a given population

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Paternity Testing

• Thomas Jefferson example
• By studying a set of 19 Y-linked markers
  (biallelic, microsatellites and minisatellites),
  it was found that Thomas Jefferson and his
  slaves child share the same haplotype.
• Frequency of haplotype was less than 1 must be
  the father

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Forces Driving Y Chromosome Evolution

• Mullers ratchet
• When a deleterious mutation occurs on the NRPY,
  the mutation must be passed down to the next
  generation.
• WHY?
• Genetic hitch-hiking
• The fixation of deleterious mutations on the Y
  chromosome that are linked with other beneficial
  genes

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• Background Selection
• The fixation of deleterious mutations results in
  the removal from the population of the
  chromosomes carrying these mutations and their
  associated alleles.
• Consequence of these 3 forces?
• Reduced amount of sequence diversity
• Eventual loss of some biological functions on the
  NRPY

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An example

• Out-of-Africa Theory
• States that all humans can be traced back to a
  single common ancestor that lived in Africa and
  dispersed throughout other continents
• EVIDENCE?
• Fossils
• Molecular Genetics

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Evidence

• Original evidence came from mtDNA data, but then
  was corroborated using Y chromosome phylogenies
• Researchers found greater genetic diversity among
  African populations, than they did among any
  other worldwide populations.

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References

• Baasner A. et al. Polymorphic sites in human
  mitochondrial DNA control region sequences
  population data and maternal inheritance.
  Forensic Science International. 1998 Dec 98(3)
  169-178.
• Stoneking M and Soodvall H. Human evolution and
  the mitochondrial genome Current Opinion in
  Genetics Development. 1996 Dec 6(6) 731-736.
• Wallace DC, Brown MD, and Lott MT. Mitochondrial
  DNA variation in human evolution and disease 
  Gene. 1999 Sep 238(1)211-230.
• Quintana-Murci L. Krausz C. and McElreavey K. The
  Human Y Chromosome Function, evolution, and
  disease. Forensic Science International 2001.
  118 169-181.
• Mitchell JR. and Hammer MF. Human evolution and
  the Y chromosome. Current Opinion in Genetics
  and Development 1996 6737-742.
• Brion M et al. 29 Y-chromosome SNP analysis in
  European populations. International Congress
  Series 2004 126173-75.
• Ghiani ME et al. Y-chromosome 10 locus short
  tandem repeat haplotypes in a population sample
  from Sicily Italy. Legal Medicine 2004 689-96.
• Strachnan T. and Read AP. Human Molecular
  Genetics 3. 2004. Garland Publishing.

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Statistical Analysis

• Used in an attempt to reduce sampling variance
• H (indices of Y chromosome diversity)
• Pi (relative freq. of microsatelite)
• K (number of haplotypes)
• Same thing as expected Heterozygosity
• p22pqq21
• H1-p2q2

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Correspondence analysis

• Correspondence analysis is a multivariate
  statistical technique to identify and explain the
  factors that differentiate between people.
  Correspondence uses statistical techniques to
  identify differences and similarities between a
  set of data and this correlation is plotted on
  the chart.
• Strongest correlations become separated (patterns
  of similarity)

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Poisson Distributions

• Given a Poisson process, the probability of
  obtaining exactly n successes in N trials is
  given by the limit of a binomial distribution.

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Link to Creating Family Tree

• http//www.pbs.org/wgbh/nova/israel/familywave.htm
  l
• Go here to use only the Y Chromosome to build a
  family tree

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Typing Specifics

• 4 Dinucleotide repeat markers
• YCAIIa YCAIIb
• DYS413a DYS413b
• Biallelic polymorphism distal to pseudoautosomal
  boundary
• YAP
• 15 biallelic markers