Transcript Document

The Human Genome and
Human Evolution
Y Chromosome
Dr Derakhshandeh, PhD
Outline
• Information from fossils and archaeology
• Neutral (or assumed-to-be-neutral) genetic
markers
– Classical markers
– Y chromosome
• Genes under selection
– Balancing selection:
• Balancing selection can arise by the heterozygotes having a selective
advantage, as in the case of sickle cell anemia
• It can also arise in cases where rare alleles have a selective advantage
– Positive selection
2
Why Y?
• "Adam passed a copy of his Y chromosome
to his sons
• The Y chromosome is paternally inherited
• the Y chromosome a father passes to his son
is, in large measure, an unchanged copy of
his own
3
4
• But small changes (called polymorphisms)
do occur
• passed down from generation to generation
5
CHROMOSOME CHANGES
• indels
– insertions into or deletions of the DNA at
particular locations on the chromosome
• YAP
– which stands for ”Y chromosome Alu
Polymorphism”
– Alu is a sequence of approximately 300 letters
(base pairs) which has inserted itself into a
particular region of the DNA
6
• Snips
–
–
–
–
"single nucleotide polymorphisms“
Stable indels and snips are relatively rare
so infrequent
they have occurred at any particular position in
the genome only once in the course of human
evolution
– Snips and stable Alus have been termed
"unique event polymorphisms" (UEPs)
7
• microsatellites
– short sequences of nucleotides (such as GATA)
– repeated over and over again a variable number
of times in tandem
– The specific number of repeats in a particular
variant (or allele) usually remains unchanged
from generation to generation
– but changes do sometimes occur and the
number of repeats may increase or decrease
8
• increases or decreases in the number of
repeats take place in single steps
• for instance from nine repeats to ten
• whether decreases in number are as
common as increases has not been
established
9
• Changes in microsatellite length occur
much more frequently than new UEPs
arise (Snips and stable Alus : "unique
event polymorphisms)
• while we can reasonably assume that a
UEP has arisen only once
• the number of repeat units in a
microsatellite may have changed many
times along a paternal lineage
10
The microsatellite data
• can facilitate the estimation of population
divergence times
• which can then be compared (and
contrasted) with estimated mutational ages
of the polymorphic markers
• the combination of these two kinds of data:
– offers a powerful tool with which to assess
patterns of migration, admixture, and ancestry
11
• minisatellites
– 10-60 base pairs long
– the number of repeats often extends to several
dozen
– Changes during the copying process take place
more frequently in minisatellites than in
microsatellites
12
the evolutionary clock
– the UEPs as the hour hand
– the microsatellite polymorphisms as
the minute hand
– the minisatellites as a sweep second
hand
13
a further benefit of using “Y
chromosome” to study evolution
• most of the Y chromosome does not
exchange DNA with a partner
• all the markers are joined one to another
along its entire length
• linkage of markers
14
The human Y chromosome
• can also be used to draw evolutionary trees
• the relationships of the Y chromosomes of
other primates
• The different polymorphic loci are
distinguished from each other by their chain
lengths
• it can be measured using an automatic DNA
sequencer
15
Gene scan output of microsatellite DNA
analysis from a single individual
The microsatellite peaks are sorted by size, the different colors
representing different microsatellites. The small red peaks are size
markers
16
new UEP arises in a certain man
• As the new UEP is copied from generation
to generation
• The UEP does not change but, albeit not
very often:
– increasing
– decreasing in length
• The longer the time since the UEP arose
– the greater will be the number of different UEP
allele
17
• Such a process:
–
–
–
–
differentiates one population from another
the more closely two populations
display common haplotype frequencies
the more closely related is their biological
history likely to be
18
IN ANCIENT TIMES
• only the analysis of DNA obtained from our
contemporaries
• suggested ways in which we might deduce
past history from an interpretation of those
data:
– DNA can be extracted from ancient remains
19
Amelogenin gene
• exists in two forms:
– the one on the X chromosome being different in
length from the one on Y
• Small portions of:
– cranial bones
– and teeth
• were crushed to powder and decalcified
20
The amelogenin gene
• is a single copy gene
• homologues of which are located on:
– Xp22.1-Xp22.3
– and Yp 11.2
21
Yp 11.2
22
• DNA was purified
• copied by PCR using primers flanking the region
• the size of the products was measured by agarose
gel electrophoresis
• Since Y chromosomes yield fragments 218 base
pairs long
• while X chromosome products contain 330 base
pairs
• they should be clearly distinguishable:
– if the specimen yields the shorter gene, it must
come from a Y chromosome fragment and thus
from a male.
23
Disadvantages
• DNA is often degraded
• so that continuous fragments are no
longer present
• cannot be copied
• substances may be present:
– inhibit both purification and
amplification
24
The first two human Y chromosome
marker
• studies appeared in 1985 (Casanova et al.
1985; Lucotte and Ngo 1985)
• It was not until almost a decade later that
Torroni and co-workers (1994a) published the
first Y chromosome data on Native Americans
• Numerous surveys of variation on the nonrecombining portion of the Y chromosome
(NRY)
25
Who are our closest living relatives?
Chen FC & Li WH (2001) Am. J. Hum. Genet. 68 444-456
26
• selected 53 autosomal / Y Ch intergenic
nonrepetitive DNA segments from the
• human genome and sequenced them in a
human, a chimpanzee, a gorilla, and an
orangutan.
27
The average sequence
• divergence was only 1.24% +/- 0.07% for
the human-chimpanzee pair
• 1.62% +/- 0.08% for the human-gorilla Pair
• and 1.63% +/- 0.08% for the chimpanzeegorilla pair
28
• Taking the orangutan speciation date as 12
to 16 million years ago
• an estimate of 4.6 to 6.2 million years for
the Homo-Pan divergence
• an estimate of 6.2 to 8.4 million years for
the gorilla speciation date
• gorilla lineage branched off 1.6 to 2.2
million years earlier than did the humanchimpanzee divergence
4.6 to 6.2 million
1.6 to 2.2 million
6.2 to 8.4 million
12 to 16 million
29
Phenotypic differences between
humans and other apes
*Carroll (2003) Nature 422, 849-857
30
Chimpanzee-human divergence
6-8
million
years
Chimpanzees
Hominids or hominins
Humans
31
Origins of hominids
• Sahelanthropus
tchadensis
• Chad (Central Africa)
• Dated to 6 – 7 million
years ago
• Posture uncertain, but
slightly later hominids
were bipedal
‘Toumai’, Chad, 6-7 MYA
Brunet et al. (2002) Nature 418, 145-151
32
Hominid fossil summary
Found only in Africa
Found both in Africa and outside, or only outside Africa
33
Origins of the genus Homo
• Homo erectus/ergaster
~1.9 million years ago
in Africa
• Use of stone tools
• H. erectus in Java ~1.8
million years ago
Nariokatome boy,
Kenya, ~1.6 MYA
34
Additional migrations out of Africa
• First known
Europeans date to
~800 KYA
• Ascribed to H.
heidelbergensis
35
Origins of modern humans (1)
• Anatomically
modern humans in
Africa ~130 KYA
• In Israel by ~90
KYA
Omo I, Ethiopia, ~130 KYA
36
Origins of modern humans (2)
• Modern human behaviour
starts to develop in Africa
after ~80 KYA
• By ~50 KYA, features
such as complex tools and
long-distance trading are
established in Africa
The first art? Inscribed ochre, South Africa, ~77 KYA
37
Expansions of fully modern humans
• Two expansions:
• Middle Stone Age
technology in Australia ~50
KYA
• Upper Palaeolithic
technology in Israel ~47
KYA
Lake Mungo 3, Australia, ~40 KYA
38
the Upper Paleolithic period
• In the Upper Paleolithic period:
– Neanderthal man disappears
– and is replaced by a variety of Homo sapiens
39
Routes of migration?
archaeological evidence
Upper Paleolithic
39 KYA
40 KYA
47 KYA
~130
KYA
50 KYA
Middle
Stone Age
40
Strengths and weaknesses of the
fossil/archaeological records
• Major source of information for most of the
time period
• Only source for extinct species
• Dates can be reliable and precise
14
– need suitable material, C calibration
required
41
Mixing or replacement?
42
Human genetic diversity is low
43
Modern human mtDNA is distinct
from Neanderthal mtDNA
Krings et al. (1997) Cell 90, 19-30
44
Nature Genetics 33, 266 - 275
(2003)
The application of molecular
genetic approaches to the study of
human evolution
L. Luca Cavalli-Sforza1 & Marcus W. Feldman2
45
• Haploid markers from mitochondrial DNA
and the Y chromosome have proven
invaluable for generating a standard model
for evolution of modern humans
• earlier research on protein polymorphisms
• Co-evolution of genes with language and
some slowly evolving cultural traits,
together with the genetic evolution
46
Evolutionary events affecting
genomic variation (1)
• All genetic variation is caused by mutations
• The most common and most useful for
many purposes are SNPs
• which can be detected by DNA sequencing
47
Evolutionary events affecting
genomic variation (2)
• Allelic frequencies change in populations owing to two
factors:
– natural selection:
– population variation among individual genotypes in
their probabilities of survival and/or reproduction,
random genetic drift
– next generation
– Both natural selection and genetic drift can
ultimately lead to the elimination or fixation of a
particular allele
• In the presence of mutation and in the absence of
selection:
– neutral conditions:
• the rate of neutral evolution of a finite
48
population is equal to the mutation rate!
Evolutionary events affecting
genomic variation (3)
• The earliest evidence of selection :
– heterozygotes of the hemoglobin A/S
• polymorphism have greater
resistance to malaria than do AA or
SS homozygotes
– G6PD locus:
• resistance to malaria
49
Evolutionary events affecting
genomic variation (4)
• Strong directional selection : for FOXP2
– a two amino-acid difference between the
human protein and in primates
– selectively important for the evolution of
speech and language in modern humans
50
Evolutionary events affecting
genomic variation (5)
• the agent of selection is not at all obvious:
– the CCR5 gene seems :
• related to HIV resistance
– mutations in the BRCA1 gene:
• produce an increased risk of female
breast cancer
51
Migration is another important factor
in human evolution that can
profoundly affect genomic variation
within a population
52
Summary tree of world populations.
Phylogenetic tree based on polymorphisms of 120 protein genes in 1,915
populations
Cavalli-Sforza & Feldman (2003) Nature Genet. 33, 266-275
53
For populations that are geographically
close, genetic and geographic distances are
often highly correlated
54
Cavalli-Sforza & Feldman (2003) Nature Genet. 33, 266-275
Dating the origin of our species
using genetic data (1)
• The mutation rate of the NRY is comparable to that of
nuclear DNA
• polymorphisms are more difficult to find but genealogies
are easier to reconstruct
• The greater length of DNA on the NRY (perhaps 30
million bases of euchromatic DNA) lower mutation rate
• Even though the NRY behaves effectively as a single
locus
• usually insufficient for evolutionary analyses
• it has provided results that are consistent across many
studies and in agreement with many archeological 55
High resolution history using
haploid markers
• SNPs on the NRY and mtDNA :
– higher resolution of population history
through the reconstruction of the
phylogenetic relationships of extant Y
chromosomes and mtDNA
• the Y Chromosome Consortium:
– the first two haplogroups (A and B) are
almost completely African and even
today represent mostly their descendants
56
Siberia
Eskimo
NRY
India
57
The migration of modern Homo sapiens.
begins with a radiation from East Africa to the rest of Africa about 100
kya and from the same area to Asia, southern and northern between 60
and 40 kya. Oceania, Europe and America were settled from Asia in
that order.
58
Cavalli-Sforza & Feldman (2003) Nature Genet. 33, 266-275
NRY
• Slow growth is indicated by the
accumulation of many mutations within a
branch, as in most descendants of
haplogroup A and B
• and in those of the earliest branches of
haplogroups C, D, E and F
•
59
NRY
• By contrast, when there are many branches (called
a starburst) after a specific mutation or group of
mutations, we can infer rapid growth
• The major expansions are those of haplogoup F
(seven branches) after an initial lag in population
growth, and even more remarkable is the later
expansion of haplogroup K (nine branches).
60
haplogroup K (nine branches)
• These began in the last 40 kya and led
to the major settlement of all
continents from Africa, first to Asia,
and from Asia to the other three
continents.
61
mtDNA
• The tree of mtDNA is more bushy, but
there are more haplogroups because of
the higher mutation rate!
62
mtDNA
63
mtDNA
• The earliest branches all remain in
Africa
• in both trees they clearly refer to the
slowly growing hunter-gatherers
• In both trees the major growth in
Africa is due to a late branch, taking
place in the second part of the last
100,000 years and clearly connected
with the expansion to Asia
64
Language families of the world
65
Phylogeographic studies
• Analysis of the geographical distributions of
lineages within a phylogeny
• Nodes or mutations within the phylogeny
may be dated
• Extensive studies of mtDNA and the Y
chromosome
66
Phylogenetic trees commonly
indicate a recent origin in Africa
90 (50 - 130) KYA, Hammer and Zegura
59 (40 - 140) KYA, Thomson et al.
90
69 (56 - 81) KYA, Hammer and Zegura
40 (35 - 89) KYA, Thomson et al.
80
KYA
70
60
50
40
30
20
10
0
A
B C D E F* G H
I
J K* L M N O P* Q R
Y chromosome
67
Y haplogroup distribution
A
B C D E F* G H
I
J K* L M N O P* Q R
68
Jobling & Tyler-Smith (2003) Nature Rev. Genet. 4, 598-612
69
70
71
An African origin
A
B C D E F* G H
I
J K* L M N O P* Q R
72
SE Y haplogroups
A
B C D E F* G H
I
J K* L M N O P* Q R
73
NW Y haplogroups
A
B C D E F* G H
I
J K* L M N O P* Q R
74
Did both migrations leave
descendants?
• General SE/NW genetic distinction fits twomigration model
– Basic genetic pattern established by initial
colonisation
• All humans outside Africa share same subset
of African diversity (e.g. Y: M168, mtDNA: L3)
– Large-scale replacement, or migrations were
dependent
• How much subsequent change?
75
Fluctuations in climate
4
Ice ages
0
-2
-4
-6
Antarctic
ice core data
Temperature difference (C)
2
-8
-10
100
90
80
70
60
50
Greenland ice core data
KYA
40
30
20
10
0
76
Possible reasons for genetic change
• Adaptation to new environments
• Food production – new diets
• Population increase – new diseases
77
Debate about the PaleolithicNeolithic transition
• Major changes in food production, lifestyle,
technology, population density
• Were these mainly due to movement of
people or movement of ideas?
• Strong focus on Europe
78
Estimates of the Neolithic Y
contribution in Europe
• ~22% (=Eu4, 9, 10, 11);
Semino et al. (2000)
Science 290, 1155-1159
• >70% (assuming Basques
= Paleolithic and
Turks/Lebanese/ Syrians =
Neolithic populations);
Chikhi et al. (2002) Proc.
Natl. Acad. Sci. USA 99,
11008-11013
79
The genetic legacy of Paleolithic Homo
sapiens sapiens in extant Europeans: a Y
chromosome perspective (1)
• It was derived from 22 markers of the
nonrecombining Y chromosome (NRY)
• Ten lineages account for >95% of the 1007
European Y chromosomes
• Geographic distribution and age estimates
of alleles are compatible with two
Paleolithic and one Neolithic migratory
episode (Semino et al. (2000)
80
The genetic legacy of Paleolithic Homo
sapiens sapiens in extant Europeans: a
Y chromosome perspective (2)
• that have contributed to the modern
European gene pool
• A significant correlation between the NRY
haplotype data and principal components
based on 95 protein markers was observed
• indicating the effectiveness of NRY
polymorphisms in the characterization of
human population composition and history
(Semino et al. (2000)
81
More recent reshaping of diversity
• ‘Star cluster’ Y haplotype originated in/near Mongolia ~1,000 (700-1,300) years ago
• Now carried by ~8% of men in Central/East Asia, ~0.5% of men worldwide
• Suggested association with Genghis Khan
Zerjal et al. (2003) Am. J. Hum. Genet. 72, 717-721
82
Mongolia (1)
(Zerjal et al. (2003) Am. J. Hum. Genet. 72, 717-721)
• It was found in 16 populations
• throughout a large region of Asia
• stretching from the Pacific to the Caspian
Sea
• present at high frequency:
– ∼8% of the men in this region carry it
– ∼0.5% of the world total
• behavior
83
Mongolia (2)
(Zerjal et al. (2003) Am. J. Hum. Genet. 72, 717-721)
• The pattern of variation within the lineage:
– it originated in Mongolia ∼1,000 years ago
• Such a rapid spread cannot have occurred by
chance
• it must have been a result of selection
• The lineage is carried by likely male-line
descendants of Genghis Khan
• propose that it has spread by a novel form of
social selection
84
Is the Y a neutral marker?
• Recurrent partial deletions
of a region required for
spermatogenesis
• Possible negative selection
on multiple (14/43)
lineages
Repping et al. (2003) Nature Genet. 35, 247-251
85
1.6-Mb deletion (1)
• Polymorphism for a 1.6-Mb deletion of the
human Y chromosome
• persists through balance between:
– recurrent mutation
– and haploid selection
Repping et al. (2003) Nature Genet. 35, 247-251
86
AZF
87
1.6-Mb deletion (2)
• Many human Y-chromosomal deletions:
– severely impair reproductive fitness
– precludes their transmission to the next
generation
– ensures their rarity in the population
Repping et al. (2003) Nature Genet. 35, 247-251
88
1.6-Mb deletion (3)
• 1.6-Mb deletion that persists over generations
• It is sufficiently common to be considered a
polymorphism
• They hypothesized that this deletion might affect
spermatogenesis
• because it removes almost half of the Y
chromosome's AZFc region (1.6 Mb)
• a gene-rich segment that is critical for sperm
production1
89
gr/gr deletion Y chromosomes
• lower penetrance with respect to spermatogenic failure
than previously characterized Y-chromosomal deletions
• it is often transmitted from father to son
• the existence of this deletion:
–
–
–
–
as a polymorphism
reflects a balance between haploid selection
and homologous recombination
which continues to generate new gr/gr deletions
Repping et al. (2003) Nature Genet. 35, 247-251
90
Selection in the human genome
time
Neutral
Negative
(Purifying,
Background)
Balancing
Positive
(Directional)
Bamshad & Wooding (2003) Nature Rev. Genet. 4, 99-111
91
Selection in the human genome (1)
• Natural selection leaves signatures in our genome
that can be used to identify the genes that might
underlie variation in disease resistance or drug
metabolism
• Evidence of positive selection acting on genes is
beginning to accumulate
92
Selection in the human genome (2)
• Demographic processes should affect all
loci in a similar way, whereas the effects of
selection should be restricted to specific loci
93
Demographic changes
Population has expanded in range and numbers
94
The Prion protein gene and
human disease
• Prion protein gene PRNP linked to ‘proteinonly’ diseases e.g. CJD, kuru
• A common polymorphism, M129V,
influences the course of these diseases
• the MV heterozygous genotype is protective
• Kuru acquired from ritual cannibalism was
reported (1950s) in the Fore people of
Papua New Guinea, where it caused up to
1% annual mortality
95
Creutzfeldt-Jakob Disease (CJD)
•
•
•
•
a neurodegenerative disease called Kuru
found in cannibalistic Pacific Islanders
a disorder diagnosed in one person per million
common symptoms:
– gait disorders
– jerky movements
– dementia that lead to death months after the first
appearance of symptoms
96
Balancing selection at PRNP
• Deep division between the M and V lineages, estimated at
500,000 years
• Kuru imposed strong balancing selection on the
Fore
• essentially eliminating PRNP 129 homozygotes
• Worldwide PRNP haplotype diversity and coding
allele frequencies :
– strong balancing selection at this locus
– during the evolution of modern humans
97
Effect of positive selection
Neutral
Selection
Derived allele of SNP
98
What changes do we expect?
• New genes
• Changes in amino-acid sequence
• Changes in gene expression (e.g. level,
timing or location)
• Changes in copy number
99
How do we find such changes?
• Chance
– φhHaA type I hair keratin gene inactivation in
humans
• Identify phenotypic changes, investigate
genetic basis
• Identify genetic changes, investigate
functional consequences
100
Human type I hair keratin
pseudogene φhHaA
• This mutant protein is unable to activate
hair keratin gene expression
• the nude phenotype
• has functional orthologs in the chimpanzee
and gorilla:
– evidence for recent inactivation of the human
gene after the Pan-Homo divergence
– 5. 5 million years ago
101
Inheritance of a language/speech
defect in the KE family
Autosomal dominant inheritance pattern
102
Lai et al. (2000) Am. J. Hum. Genet. 67, 357-367
A forkhead-domain gene is mutated
in a severe speech and language
disorder
• the gene FOXP2
• encodes a putative transcription factor
• Containing:
– a polyglutamine tract
– a forkhead DNA-binding domain
• disrupted by the translocation or point mutation
• the KE family that alters an invariant amino-acid
residue in the forkhead domain
103
Mutation and evolution of the
FOXP2 gene
Chr 7
7q31
Nucleotide substitutions
FOXP2 gene
silent
replacement
Enard et al. (2002) Nature 418, 869-872
104
Positive selection at the FOXP2 gene
Constant rate of amino-acid replacements?
replacement
(non-synonymous)
silent
dN
(synonymous)
dS
Orang
Gorilla
Chimp
Human
Positive selection in humans?
• Resequence ~14 kb
of DNA adjacent to
the amino-acid
changes in 20
diverse humans,
two chimpanzees
and one orang-utan
Human-specific increase in dN/dS ratio (P<0.001)
Enard et al. (2002) Nature 418, 869-872
105
A gene affecting brain size
Microcephaly (MCPH)
• Small (~430 cc v ~1,400
cc) but otherwise ~normal
brain, only mild mental
retardation
• MCPH5 shows Mendelian
autosomal recessive
inheritance
• Due to loss of activity of
the ASPM gene
ASPM-/ASPM-
control
Bond et al. (2002) Nature Genet. 32, 316-320
106
Evolution of the ASPM gene (1)
Summary dN/dS values
Sliding-window dN/dS analysis
0.62
0.52
0.53
1.44
0.56
Orang
Gorilla
0.56
Chimp
Human
Human-specific increase in dN/dS ratio (P<0.03)
107
Evans et al. (2004) Hum. Mol. Genet. 13, 489-494
What changes?
• The Drosophila homolog of ASPM codes for a
microtubule-binding protein that influences
spindle orientation and the number of neurons
asp
Microtubules
DNA
do Carmo Avides and Glover (1999) Science 283, 1773-1735
• Subtle changes to the function of well-conserved
genes
108
Genome-wide search for protein
sequence evolution
• 7645 human-chimp-mouse gene compared
• Most significant categories showing positive
selection include:
–
–
–
–
Olfaction: sense of smell
Development: e.g. skeletal
Hearing: for speech perception
brain size: IQ
Clark et al. (2003) Science 302, 1960-1963
109
Gene expression differences in human
and chimpanzee cerebral cortex
• Affymetrix oligonuclotide array (~10,000) genes
• 91 show human-specific changes, ~90% increases
Increased expression
Decreased expression
Caceres et al. (2003) Proc. Natl. Acad. Sci. USA 100, 13030-13035
110
Copy number differences between
human and chimpanzee genomic DNA
Human male reference genomic DNA hybridised with female chimpanzee genomic DNA
111
Locke et al. (2003) Genome Res. 13, 347-357
Selection at the CCR5 locus
• CCR532/CCR532 homozygotes are
resistant to HIV and AIDS
• The high frequency and wide distribution of
the 32 allele suggest past selection by an
unknown agent
112
The Role of the Chemokine
Receptor Gene CCR5 and Its Allele (
del32 CCR5)
• Since the late 1970s
• 8.4 million people worldwide
• including 1.7 million children, have died of
AIDS
• an estimated 22 million people are infected
with human immunodeficiency virus (HIV)
113
CCR5 and Its Allele ( del32 CCR5)
monocyte/macrophage (M),
T-cell line (Tl)
a circulating T-cell (T)
114
Lactase persistence
• All infants have high lactase enzyme
activity to digest the sugar lactose in milk
• In most humans, activity declines after
weaning, but in some it persists:
LCT*P
115
Molecular basis of lactase persistence
• Lactase level is controlled by a cis-acting element
• Linkage studies show association of lactase
persistence with the T allele of a T/C polymorphism
14 kb upstream of the lactase gene
Enattah et al. (2002) Nature Genet. 30, 233-237
116
The lactase-persistence haplotype
• The persistenceassociated T allele
occurs on a
haplotype (‘A’)
showing over > 1 Mb
• Association of lactase
persistence and the A
haplotype is less clear
outside Europe
117
Selection at the G6PD gene by malaria
• Reduced G6PD enzyme activity (e.g. A allele)
confers some resistance to falciparum malaria
Extended haplotype homozygosity at the A allele
Sabeti et al. (2002) Nature 419, 832-837
118
Final words
Is there a genetic continuum between us and our
ancestors and the great apes?
If there is, then we can say that:
these [i.e. microevolutionary] processes
are
genetically sufficient to fully account
for human
uniqueness
119