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2012/4/29
Chapter 24
Evolutionary Genetics
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Chapter Outline
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The Emergence of Evolutionary Theory
Genetic Variation in Natural Populations
Molecular Evolution
Speciation
Human Evolution
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Darwin’s Theory of Evolution
• A species changes as a result of generations of competition among individuals.
competition among individuals.
• Within a species, individuals vary with respect to heritable characteristics that influence the ability to survive and reproduce.
• Individuals possessing characteristics that enhance survival and reproduction have more offspring than other individuals.
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Natural Selection
• Because of the unequal contribution to the next generation characteristics that enhance survival and
generation, characteristics that enhance survival and reproduction tend to become more frequent within the species.
• Over many generations, natural selection changes the characteristics of the species
the characteristics of the species.
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Artificial Selection has Changed Domesticated Species
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Finches on the Galapagos Islands
• Darwin observed several species finches on the Galapagos Islands
Galapagos Islands.
• He recognized that these species were related to each other and to birds on the South American mainland.
• This led Darwin to the view that species are not fixed entities but may change over time and may become extinct.
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Evolutionary Genetics
• Darwin’s theory did not explain the origin of variation among individuals or explain the
variation among individuals or explain the inheritance of particular variants.
• The rediscovery of Mendel’s principles in 1900 led to the discipline of evolutionary genetics through the contributions of Wright, Risher, and Haldane.
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Key Points
• Charles Darwin formulated a theory in which species evolve through natural selection.
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• After the rediscovery of Mendel’s work, Darwin’s ideas became grounded on Mendelian principles of inheritance
Mendelian principles of inheritance.
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Genetic Variation in Natural Genetic
Variation in Natural
Populations
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Naturally Occurring Phenotypic Variation
• In Drosophila, many mutant alleles have been characterized for phenotypes such as eye color and
characterized for phenotypes such as eye color and body color, but most of these alleles are not common enough to be considered part of a polymorphism.
• Light and dark forms of the peppered moth in Great Britain are due to different alleles of a single gene. Th
The status of this polymorphism has changed since f hi
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the 19th century.
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A Human Polymorphism
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Variation in Chromosome Structure
• Drosophila polytene chromosomes afford researchers an opportunity to look for variation in chromosome structure in natural populations.
• Theodosius Dobzhansky identified many rearrangements of the banding patterns in the polytene chromosomes, each consisting of one or more inversions.
• Changes in the frequencies of these patterns over time suggests that balancing selection helps to maintain these chromosome polymorphism in nature.
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Variation in Protein Structure
• Amino acid differences in proteins can be d t t d i
detected using gel electrophoresis.
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• Proteins differing in size and charge can be separated by moving them through a starch or polyacrylamide gel
polyacrylamide gel.
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Isocitrate Dehydrogenase Variability in Trillium pusillium
• Isocitrate dehydrogenase exists as a dimer.
• Electrophoresis can distinguish dimers containing El t h
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two fast‐moving subunits, two slow‐moving subunits, and a “hybrid” enzyme with one fast and one slow enzyme subunit. • The fast‐ and slow‐moving subunits are allozymes
encoded by different alleles of the same gene.
• The three types of bands on a gel correspond to the two homozygotes and the heterozygote, respectively.
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Protein Polymorphisms
• Proteins that exhibit electrophoretic variation are polymorphic if at least two of the variants have
polymorphic if at least two of the variants have frequencies greater than 1% in the population.
• Proteins that do not exhibit electrophoretic variation are monomorphic.
• The proportion of genes in a species that are polymorphic and the proportion of individuals that are heterozygous are a measure of genetic variability h
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within a population.
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Variation in Nucleotide Sequences
• DNA sequencing can be used to study genetic variation. Any DNA sequence can be analyzed.
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Polymorphisms in the Alcohol Dehydrogenase Gene of Drosophila
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• Most of the polymorphisms in the Alcohol dehydrogenase (Adh) gene are in noncoding regions (introns
regions (introns and 3
and 3' and 5
and 5' untranslated regions).
• Most of the polymorphisms in the coding region are silent and rise from the degeneracy of the genetic code.
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Key Points
• Genetic variation in natural populations can be detected at the phenotypic chromosomal
be detected at the phenotypic, chromosomal, and molecular levels.
• Classic studies established the existence of genetic polymorphisms for conspicuous phenotypic traits and for blood types.
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Key Points
• Polymorphisms in chromosome structure have been documented in various species of Drosophila by documented in various species of Drosophila
by
analyzing banding patterns in the polytene chromosomes.
• Polymorphisms in polypeptide structure have been detected by using the technique of protein gel
detected by using the technique of protein gel electrophoresis.
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Key Points
• Polymorphisms in DNA structure have been d t t db
detected by sequencing cloned or PCR‐
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amplified DNA, and by using diagnostic gene chips.
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M l l E l i
Molecular Evolution
DNA and protein sequences provide information on the phylogenetic relationships among different organisms, and on their evolutionary history.
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Molecular Evolution
• Heredity depends on the sequence of nucleotides in DNA and the transmission of DNA molecules from
DNA and the transmission of DNA molecules from parents to offspring.
• When mutations occur, modified DNA molecules are transmitted to the offspring.
• Over time, mutations accumulate and the DNA sequence is changed; chromosomal rearrangements may also occur.
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• Molecular evolution underlies the evolution of organisms.
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Evolutionary History
• Comparisons between living organisms and fossils stimulated Darwin and others to speculate about the
stimulated Darwin and others to speculate about the origin of species.
• The DNA molecules in today’s organisms are derived from their ancestors and therefore contain information about evolutionary history.
• Evolution can be studied at the molecular level by analyzing nucleotide and amino acid sequences.
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DNA and Protein Sequence Analysis vs. Traditional Methods to Study Evolution
• DNA and protein sequences follow simple rules of heredity.
• Molecular sequence data are easy to obtain and are amenable to quantitative analyses framed in evolutionary genetics theory.
• Molecular sequence data allow analysis of evolutionary relationships among organisms that are phenotypically very dissimilar.
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Molecular Phylogenies
• Evolutionary relationships among organisms are summarized in phylogenetic trees, or phylogenies.
summarized in phylogenetic
trees, or phylogenies.
• A phylogeny that shows only the relationships among organisms is an unrooted tree.
• A
A phylogeny that superimposes the relationships on phylogeny that superimposes the relationships on
a time scale to show how organisms evolved is a rooted tree.
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Phylogenetic Trees
• Lineages bifurcate to produce branches.
• The terminal branches lead to the organism being studied.
• Each bifurcation represents a common ancestor.
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Homologous Sequences
• The descendants of an ancestral DNA or protein sequence are homologous.
sequence are homologous.
• Sequences that resemble each other but are derived from different ancestral sequences are analogous.
• Construction
Construction of phylogenetic
of phylogenetic trees should be
trees should be based based
on homologous sequences.
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Steps Involved in Constructing Phylogenetic Trees
• Ali
Aligning the sequences to allow i th
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comparisons among them
• Ascertaining the amount of similarity or difference between any two sequences
• Grouping the sequences on the basis of Grouping the sequences on the basis of
similarity
• Placing the sequences at the tips of trees
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Parsimony
• The principle of parsimony is used to judge th
the merit of a tree.
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• The best tree is the one that requires the fewest mutational changes.
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Mutational
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Phylogenetic Trees of Hominids Based f H i id B d
on Mitochondrial DNA
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Rates of Molecular Evolution
• If the branch points of a tree can be linked to specific times in the evolutionary history of a ifi ti
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species, then we can determine the rate at which the sequences have been evolving.
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Phylogeny of Vertebrates Based on the Fossil Record
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Estimating the Mutation Rate
• The phylogenetic tree of vertebrates based on the fossil record is consistent with the comparisons of ‐
fossil record is consistent with the comparisons of 
globin sequences.
• To estimate the mutation rate, we need to determine that average number of amino acid changes that have occurred since any two lineages split from a common ancestor.
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• Between humans and mice, 16 of 141 amino acid sites in ‐globin differ, so the proportion of different sites is 16/141 = 0.11.
• Between humans and carp, the proportion of different sites is 68/141 = 0.48.
• Some sites could have mutated more than once, so 0.48 probably underestimates the average number of changes that have occurred since the
number of changes that have occurred since the human and carp lineages diverged. This can be adjusted using the Poisson correction.
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The Molecular Clock
• Analysis of ‐globin and other protein sequences suggests that amino acid substitutions have occurred
suggests that amino acid substitutions have occurred at a constant rate over time.
• A universal molecular clock does not apply to all evolving lines, but within some lines, local clocks may be operating
be operating.
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Using Molecular Clocks
• With a molecular clock, we can use the estimated rate of evolution to calculate the ti t d t f
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time since two lineages diverged from a common ancestor.
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• Human and kangaroo ‐globins differ in 26 of 141 sites, or 0.18, which can be corrected to 0.20 using the Poisson g
distribution.
• The estimated evolutionary rate of ‐globin for mammals is 0.74 substitutions per site every billion years.
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• The total evolutionary time since the human and kangaroo lineages split is 0 20/0 74  10‐9 = 270 my.
0.20/0.74 
270 my
• This time must be divided equally between the two lineages, so the time since the human and kangaroo lineages diverged is
human and kangaroo lineages diverged is 270my/2 = 135 my. © John Wiley & Sons, Inc.
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Variation in Evolutionary Rates
• The ‐globin polypeptide is evolving at a rate of slightly less than one amino acid substitution per site every billion years.
• Observed rates of amino acid sequence evolution range over three orders of magnitude, at rates between 0.01 and 8 amino acid substitutions per site every billion years.
• Different amino acid sites within the same polypeptide may evolve at different rates.
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Explanation of Variation in Evolutionary Rates
• Variation in evolutionary rates can be explained by the amount of
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constraint on the amino acid sequence.
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Variation in the Evolutionary Rates of DNA Sequences
• Pseudogenes (duplicated genes that do not encode functional products) have the highest evolutionary
functional products) have the highest evolutionary rates.
• Different parts of genes evolve at different rates.
In coding regions, synonymous substitutions are coding regions, synonymous substitutions are
• In
more common than nonsynonymous substitutions.
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The Neutral Theory of Molecular Evolution
• Mutation is the source of all nucleotide and amino acid substitutions that occur during evolution
acid substitutions that occur during evolution.
• Purifying selection eliminates mutations that depress fitness.
• Random genetic drift determines the fate of a selectively neutral mutation. The rate of fixation is equal to the neutral mutation rate
equal to the neutral mutation rate.
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Fixation of Selectively Neutral Mutations
• Assume that the population size is N and that in each generation, a fraction u of the 2N
generation, a fraction u
of the 2N copies of a gene copies of a gene
mutate to unique, selectively neutral alleles.
• Each generation, the number of selectively neutral mutations that appear will be 2Nu.
• The frequency of each mutation is 1/2N.
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• With random genetic drift, the probability that a neutral allele will ultimately be fixed is the allele’s current frequency, or 1/2N.
• The rate at which selectively neutral mutations are fixed is the number of new mutations that appear each generation (2Nu) times the probability that any one of them will ultimately be fixed (1/2N), or 2Nu
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 (1/2N) = u.
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• For selectively neutral mutations, the rate of molecular evolution is equal to the rate at which these mutations occur in the population.
• The rate of evolution does not depend on population size, the efficiency of selection, or the mating system.
• If the neutral mutation rate is constant, then ,
nucleotide and amino acid substitutions should occur in clocklike fashion in all evolving lineages.
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• For some positions within a sequence, nearly all mutations will be selectively neutral.
• For other positions, few or no mutations will be selectively neutral.
• The Neutral Theory explains the variation in evolutionary rates among protein and DNA regions.
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Molecular Evolution and Phenotypic Evolution
• Neutral Theory does not explain the evolution of adaptive traits
of adaptive traits.
• Adaptations evolve due to positive selection.
• The evolution of adaptations leads to the p
diversification of organisms.
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“Living Fossils” Have Changed at the Molecular Level but not at the Phenotypic Level
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Gene Duplication
• Genes often become duplicated in evolution.
• Duplications sometimes acquire different functions.
• Gene duplication can lead to phenotypic evolution.
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Gene Duplication in the Evolution of the Globin Genes
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Exon Shuffling
• Walter Gilbert hypothesized that each exon in a gene encodes a separate functional domain in the gene’ss encodes a separate functional domain in the gene
polypeptide product.
• Exons from one gene could be combined with exons from another gene to specify a a novel protein with some of the properties of each original gene product.
• DNA sequencing studies have provided support for DNA sequencing studies have provided support for
this hypothesis.
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Exon Shuffling in the Gene for Tissue Plasminogen Activator
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Changes in Gene Expression
• Spatial
Spatial and temporal changes in the and temporal changes in the
expression gene have also led to evolutionary diversification.
• In Drosophila, altering the expression of one or more homeobox gene can change one or more homeobox
gene can change
the appearance of the fly dramatically.
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Key Points
• Phylogenetic trees based on the comparison of DNA and protein sequences show the evolutionary
and protein sequences show the evolutionary relationships among organisms.
• The rate of molecular evolution can be determined by calculating the average number of amino acid or nucleotide changes that have occurred per site in a molecule since two or more evolving lineages l l i
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diverged from a common ancestor.
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Key Points
• The near uniformity of the rate of molecular evolution in different lineages is metaphorically
evolution in different lineages is metaphorically described as a “molecular clock.”
• The rate of evolution varies among different protein and DNA sequences and appears to depend on the extent to which these sequences are constrained by natural selection to preserve their function.
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Key Points
• Selectively neutral mutations are fixed in a population at a rate equal to the neutral mutation
population at a rate equal to the neutral mutation rate.
• Gene duplication and exon shuffling have played important roles in evolution.
• Changes in the spatial and temporal aspects of gene regulation may have contributed to the rapid evolution of some types of organisms.
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S i ti
Speciation
Species arise when a population of organisms splits into genetically distinct groups that can no longer interbreed with each other.
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What Is a Species?
• A species is a group of organisms that share characteristics.
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• Species have been defined in different ways.
– Traditionally, species have been defined based on phenotypic characteristics. – In evolutionary genetics, a species is a group of interbreeding, or potentially interbreeding, organisms i
is reproductively isolated from other species.
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• These two methods are not always in agreement.
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Reproductive Isolation
• Prezygotic isolating mechanisms prevent members of different groups from producing
members of different groups from producing hybrid offspring.
• Postzygotic isolating mechanisms prevent hybrid offspring from passing on their genes t
to subsequent generations.
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Prezygotic Isolating Mechanisms
• Prezygotic isolating mechanisms prevent matings
between individuals form different populations of organisms or by preventing the gametes of these
organisms or by preventing the gametes of these individuals to form zygotes.
• These mechanisms include
– Ecological isolation based on habitat preference (different habitats in the same geographical area)
– Temporal or behavioral factors (e.g., different times sexual maturity or different courtship rituals)
– Anatomical or chemical incompatibilities in reproductive organs or gametes (e.g., failure to mate successfully or to form zygotes)
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Postzygotic Isolating Mechanisms
• Postzygotic isolating mechanisms operate after hybrid zygotes have been formed.
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• Mechanisms include
– Reduction of hybrid viability (e.g., failure to survive or to reach sexual maturity)
– Impaired hybrid fertility (failure to produce p
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y(
p
functional gametes)
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Allopatric Speciation
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Sympatric Speciation
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The Genetics of Speciation
• The genetics of speciation is difficult to study because of reproductive isolation.
because of reproductive isolation.
• Closely related species of Drosophila can be crossed and sometimes produce viable hybrids.
• Hybrid inviable seems to involve the products of at least 200 genes.
• In addition to the effects of individual genes, chromosomal differences may contribute to reproductive isolation by causing sterility.
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Key Points
• In evolutionary genetics, a species is a group of populations that share a common gene pool
populations that share a common gene pool.
• The development of reproductive isolation between populations is the key event in the speciation process.
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Key Points
• Speciation may occur when the populations are geographically separated (allopatric) or when they
geographically separated (allopatric) or when they coexist in the same territory (sympatric).
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H man E ol tion
Human Evolution
Fossil evidence and DNA sequence analysis have provided information about the origin of modern humans.
about the origin of modern humans.
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Fossil Evidence of Human Evolution
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Hypotheses about Human Evolution
• The Multiregional Hypothesis proposes that modern humans evolved simultaneously in Europe, Asia, and Africa from the archaic human populations that existed on those continents.
• The Out‐of‐Africa Hypothesis proposes that humans evolve don one continent (probably Africa) and subsequently spread to the others.
• Fossil evidence cannot distinguish between these hypotheses, but they can be tested with genetic evidence.
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DNA Sequence Variation and Human Origins
• Populations that are closely related share genetic properties that distantly related
genetic properties that distantly related populations do not.
• Genes, gene products, and DNA sequences can be analyzed for variation to study relatedness and to construct phylogenetic l t d
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t t h l
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trees.
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Genetic Variation Used to Study Human Evolution
• Blood group polymorphisms
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• Allozyme polymorphisms
• Variation in DNA sequences, including nuclear DNA and mitochondrial DNA, which is transmitted exclusively through females
is transmitted exclusively through females.
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Genetic Variation in Human Populations
• Compared to other species, the human species is genetically rather uniform.
genetically rather uniform.
• Most genetic variation in humans is within rather than between populations.
• This implies that during evolutionary history, the genetically effective size of the human population was small. This suggests that drift has dominated over mutation for selectively neutral alleles. © John Wiley & Sons, Inc.
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A Coalescence Process
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A Common Ancestor
• Mitochondrial DNA sequences and DNA sequences on the Y chromosome can be analyzed and represent
on the Y chromosome can be analyzed and represent maternal and paternal common ancestors, respectively.
• The coalescent principle suggests that all modern humans are descended from maternal and paternal
humans are descended from maternal and paternal common ancestors who lived 100,000 to 200,000 years ago.
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Phylogeny of Human Populations Based on Analysis of SNPs
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Key Points
• Fossil evidence indicates that the remote ancestors of human beings evolved in Africa beginning about 4 to
human beings evolved in Africa, beginning about 4 to 5 million years ago.
• Genetic evidence indicates that modern human populations may have emerged from Africa about 100 000 to 200 000 years ago and subsequently
100,000 to 200,000 years ago and subsequently spread to other continents.
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