Abstract
In
Charles Darwin’s tree model for life’s evolution, natural selection
adaptively modifies newly arisen species as they branch apart from their
common ancestor. In accord with this Darwinian concept, the
phylogenomic approach to elucidating adaptive evolution in genes and
genomes in the ancestry of modern humans requires a well supported and
well sampled phylogeny that accurately places humans and other primates
and mammals with respect to one another. For more than a century, first
from the comparative immunological work of Nuttall on blood sera and now
from comparative genomic studies, molecular findings have demonstrated
the close kinship of humans to chimpanzees. The close genetic
correspondence of chimpanzees to humans and the relative shortness of
our evolutionary separation suggest that most distinctive features of
the modern human phenotype had already evolved during our ancestry with
chimpanzees. Thus, a phylogenomic assessment of being human should
examine earlier stages of human ancestry as well as later stages. In
addition, with the availability of a number of mammalian genomes,
similarities in phenotype between distantly related taxa should be
explored for evidence of convergent or parallel adaptive evolution. As
an example, recent phylogenomic evidence has shown that adaptive
evolution of aerobic energy metabolism genes may have helped shape such
distinctive modern human features as long life spans and enlarged brains
in the ancestries of both humans and elephants.
Charles
Darwin proposed that natural selection favors inherited modifications
that better adapt the organisms of a species to the environment of that
species (1).
Darwin also proposed the tree model for life’s evolution. In this
model, natural selection adaptively modifies newly arisen species as
they branch apart from their common ancestor (1).
Although there is now evidence that symbiotic merges produced the first
eukaryotes and that prokaryotic species engage in reticulate evolution (2⇓–4),
Darwin’s model of tree-like branching appears to hold for the evolution
of primates and other vertebrates. Having deduced that species share
common ancestors, Darwin also reasoned that a truly natural system for
classifying species would be genealogical, i.e., species should be
classified according to how recently they last shared a common ancestor.
The hierarchical ranking in such a genealogical system could then be
used to indicate how relatively close or distant in geological time
extant species are from their last common ancestor (LCA).
In
accord with this Darwinian framework, the phylogenomic approach to
elucidating adaptive evolution in the ancestry of modern humans involves
identifying the changes in genes and genomes on a phylogenetic tree
that accurately places humans within the order Primates and, more
widely, within the class Mammalia. Viewing the ancestries of many
mammals, not just the ancestry of modern humans, could provide examples
of convergent adaptive evolution, which may point to specific categories
of genetic changes that are associated with important phenotypic
changes. This phylogenomic approach could help identify the positively
selected genetic changes that shaped such distinctive modern human
features as prolonged prenatal and postnatal development, lengthened
life spans, strong social bonds, enlarged brains, and high cognitive
abilities. In this article, we first briefly sketch out the historical
background of ideas and findings that have led to phylogenomic studies
of human evolution. We then highlight the concepts that motivate our own
efforts and discuss how phylogenomic evidence has enhanced our
understanding of adaptive evolution in the ancestry of modern humans.
Darwin’s Views
In The Descent of Man, and Selection in Relation to Sex (5), Charles Darwin suggested that Africa was the birthplace for humankind. The following five passages encapsulate for us Darwin’s thinking about the place of humans in primate phylogeny and about the uniqueness of modern humans.- If the anthropomorphous apes be admitted to form a natural subgroup, then as man agrees with them, not only in all those characters which he possesses in common with the whole Catarhine group, but in other peculiar characters, such as the absence of a tail and of callosities, and in general appearance, we may infer that some ancient member of the anthropomorphous subgroup gave birth to man (ref. 5, p. 160).
- It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man’s nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere (ref. 5, p. 161).
- In regard to bodily size or strength, we do not know whether man is descended from some small species, like the chimpanzee, or from one as powerful as the gorilla; and, therefore, we cannot say whether man has become larger and stronger, or smaller and weaker, than his ancestors. We should, however, bear in mind that an animal possessing great size, strength, and ferocity, and which, like the gorilla, could defend itself from all enemies, would not perhaps have become social: and this would most effectually have checked the acquirement of the higher mental qualities, such as sympathy and the love of his fellows. Hence it might have been an immense advantage to man to have sprung from some comparatively weak creature (ref. 5, p. 65).
- As far as differences in certain important points of structure are concerned, man may no doubt rightly claim the rank of a Suborder; and this rank is too low, if we look chiefly to his mental faculties. Nevertheless, from a genealogical point of view it appears that this rank is too high, and that man ought to form merely a Family, or possibly even only a Subfamily (ref. 5, p. 158).
- Nevertheless the difference in mind between man and the higher animals, great as it is, certainly is one of degree and not of kind (ref. 5, p. 130).
Darwin’s
application of the theory of evolution by natural selection to
discussions of our own origins and place within nature laid the
foundation for modern phylogenetic and phylogenomic studies of human
evolution. He proposed that humankind originated from man-like apes
(first quote) in Africa and that humans are most allied to chimpanzees
and gorillas (second quote). Further, Darwin seems to have thought that
our progenitors were more like chimpanzees than gorillas (third quote).
Darwin challenged the then orthodox view that a whole taxonomic order,
the Bimana, should consist of only one species, our own Homo sapiens.
Instead, Darwin noted that genealogically, we humans should have no
more than a family or even just a subfamily to ourselves (fourth quote),
suggesting that Darwin might have been willing to have a family
Hominidae that grouped modern humans with man-like apes. Moreover,
Darwin also commented on the most widely cited example of human
uniqueness, the modern human mind. He postulated that the difference
between the modern human mind and the mind of other higher animals was
one of degree not of kind (fifth quote). Nearly a century after Darwin
first proposed the theory of evolution by natural selection, molecular
evolution emerged as a scientific field and molecular methods began to
be used toward the study of human evolution. Molecular evidence inferred
from proteins and DNA data generated during the past 50 years have
vindicated Darwin’s foresightedness and have decisively established that
among living species modern humans have their closest kinship to common
and bonobo chimpanzees.
Use of Molecular Methods to Infer Our Place in Nature
More than 100 years ago, Nuttall (6)
observed that rabbit antiserum produced against human whole-blood serum
yielded larger precipitates when mixed with serum from human,
chimpanzee, or gorilla blood than from orangutan, gibbon, or other
mammalian blood. Although Nuttall did not comment on the possible
phylogenetic and taxonomic significance of his antihuman serum
cross-reacting more strongly with chimpanzee and gorilla sera than with
Asian ape sera, he did foresee a promising future for molecular studies
of evolution (6).
By
the middle of the 20th century, molecular biologists had established
that DNA contained the genetic information for an organism and that
nucleotide sequences in genes encoded the amino acid sequences of
proteins. Immunologists could then deduce that a protein’s antigenic
divergencies among species reflected amino acid sequence divergencies,
the source of which were nucleotide sequence substitutions. An
immunological method that was much improved over Nuttall’s was used to
examine protein divergencies among primate and other mammalian species (7⇓⇓⇓–11).
The observed protein divergencies, interpreted as genetic divergencies, challenged the reigning view (12)
that the human lineage diverged markedly from the ancestral ape state
to occupy an entirely new structural–functional adaptive zone. Whereas
the then-prevailing view placed chimpanzees and gorillas with orangutans
in the family Pongidae, with humans alone among living species in the
family Hominidae (12),
the immunologically detected genetic affinities showed humans,
chimpanzees, and gorillas to be highly similar and more closely related
to one another than to orangutans or other primates, thus supporting
chimpanzees and gorillas being grouped with humans in the family
Hominidae (9⇓–11).
The indicated genetic kinship between chimpanzees and gorillas was not
any closer than the close kinship of either to humans. Indeed some
immunological results placed chimpanzees closer to humans than to
gorillas (e.g., Fig. 4 in ref. 10), and they also suggested that rates of molecular evolution had slowed in hominoid lineages (7⇓⇓–10).
Thus, these first substantial molecular data did not support the claim
that the human lineage had diverged radically from an ancestral ape
state. Instead, in their proteins, humans, chimpanzees, and gorillas
diverged only slightly from one another. The degrees of interspecies
antigenic divergence of serum albumin challenged the conventional view
that many millions of years of evolution separated modern humans from
our nearest nonhuman relatives (13, 14).
Instead when these immunologic divergence data were analyzed by a
molecular clock model the LCA of humans, chimpanzees, and gorillas was
placed at only 5 Mya (13, 14).
The determination of the actual amino acid sequences of proteins began in the 1950s (15)
and, in the ensuing decades, provided important information about human
evolution. Phylogenetic analysis of hemoglobin amino acid sequences
pointed to the possibility that chimpanzees and humans were more closely
related to each other than either was to gorillas (16⇓–18). This analysis grouped chimpanzee and gorilla with human rather than with orangutan hemoglobin (17, 18) and showed human and chimpanzee hemoglobin to be identical and slightly divergent from gorilla hemoglobin (16⇓–18).
Estimates
of interspecies genetic similarities were also obtained by DNA–DNA
hybridization data. An initial set of such data reported in 1972 (19),
similar to the hemoglobin amino acid sequence data, suggested that
instead of a human–chimpanzee–gorilla trichotomy, humans and chimpanzees
shared the more recent common ancestor. During the 1980s, extensive
DNA–DNA hybridization data clearly placed chimpanzees closer to humans
than to gorillas (20, 21).
Direct measurements of interspecies genetic similarities were provided
by the actual nucleotide sequences of orthologous DNAs, each set of
these DNA orthologues apparently having descended from the same genomic
locus in the LCA of the examined contemporary species. By the late 1980s
and early 1990s, phylogenetic analysis of such data greatly
strengthened the evidence that chimpanzees (common and bonobo) have
humans, not gorillas, as their closest relatives (22⇓–24).
With
the advent of next-generation sequencing technologies, genomic-level
sequence data have provided strong evidence that chimpanzees are our
closest living relatives and only slightly diverge from us (25⇓⇓⇓⇓–30).
Large amounts of nucleotide sequence data have also been used to infer
the evolutionary relationships among almost all extant primate genera (26, 31) and among the major clades of placental mammals (32⇓–34).
These data reveal that rates of molecular evolution were slower in apes
than in Old World monkeys and, within the ape clade, slower in
chimpanzees than in gorillas and orangutans and slowest in the human
lineage (27, 35).
This slowdown can be attributed to the decreased annual mutation rates
that must have resulted from lengthened generation times. There may also
have been selection for more efficient mechanisms of DNA repair and
maintenance of genome integrity (36).
A
number of recent studies have used fossil calibration points and a
variable-rate molecular clock to infer divergence dates across primate
phylogeny (e.g., refs. 31, 37⇓–39).
Dates inferred from the fossil record and molecular data suggest the
human–chimpanzee LCA is more recent than the LCA age for the species of a
strepsirrhine genus (either lemuriform or lorisiform) and is close to
the LCA age for the species of an Old World monkey genus such as Macaca or Cercopithecus or a New World monkey genus such as Ateles or Callicebus.
This objective view of our species recalls Darwin’s vision of our place
in a genealogical classification of primates. However, these data
suggest that, rather than having a mere subfamily to ourselves, we
modern humans should perhaps have no more than a genus or just a
subgenus to ourselves, i.e., common and bonobo chimpanzees and modern
humans would be the only extant members of either subtribe Hominina or
genus Homo (30, 40, 41). The rules (42)
for such an age-based genealogical classification are that each taxon
should represent a clade, and clades at an equivalent evolutionary age
should be assigned the same taxonomic rank. An intragenus
sister-grouping of humans and chimpanzees is concordant with the ages of
origin of many other mammalian genera (43)
and captures the close genetic correspondence of humans to chimpanzees.
In accord with this close correspondence, chimpanzees are highly
social, have simple material cultures, inhabit a wide range of habitats
that range from forests to savannas, and have the ability to use
rudimentary forms of language (44⇓⇓⇓⇓–49).
Phylogenomic Assessment of Being Human
The extensive sequencing of genomes from primates (Fig. 1)
and other vertebrates makes possible a phylogenomic search for the
genetic basis of modern human traits. The close genetic correspondence
of chimpanzees to humans and the relative shortness of our evolutionary
separation from chimpanzees suggest that most of the adaptive evolution
that produced the distinctive modern human phenotype had already
occurred by the time of the LCA of chimpanzees and humans. Thus, an
assessment of the genetic underpinnings of being human should not just
focus on the terminal human lineage but should also encompass earlier
periods of human ancestry (Fig. 2).
Moreover, there are other mammals with aspects of their phenotypes
(e.g., enlarged brains) that are similar to aspects of the distinctive
modern human phenotype. Examining the ancestries of these mammals is a
further way to assess the genetic underpinnings of distinctive modern
human phenotypic features and suggests that all such features are not
necessarily unique to modern humans.
Fig. 1.
Summary
of primate genome sequencing projects based on the National Human
Genome Research Institute list of the status of approved sequencing
targets (current as of December 15, 2009). Species shown in purple (+)
are completed, those in pink (^) are in progress, and that in green (*)
has not yet been started. **Sequencing of the Neanderthal genome is
currently in progress, although not listed by the National Human Genome
Research Institute. Nodes of particular interest for examining the
evolutionary origins of distinctive human traits are noted by a black
oval.
Fig. 2.
Lineages
of interest when examining the evolutionary origins of distinctly human
traits using currently available high-quality genomic data.
Phylogenomic Assessment of Human Brain Evolution Reveals Adaptive Evolution in Multiple Stages of Human Ancestry
Expanded
cognitive abilities are hallmarks of modern humans. Why such abilities
were selected for in modern humans and in the human lineage, and how
they are maintained, is of great interest. As noted by Darwin more than
135 years ago, differences observed between the modern human mind and
the mind of our closest living relatives can be more appropriately
characterized as differences in degree, not differences in absolute
kind. As such, we expect that the roots of the adaptive evolution that
led to the modern human mind trace back to ancient stem lineages in
primate and mammalian phylogeny. For example, humans have a phenomenal
ability to design and use complex tools, but this ability depends on the
opposable thumb, which had evolved in the early primates, as attested
to by its presence in slow loris and other primate species.
A
striking morphological feature that separates modern humans from other
primates is our enlarged cerebral cortex. An initial enlargement of the
cerebral cortex in the stem lineage of the anthropoid infra-order
Catarrhini was followed by further marked enlargements in the hominid
lineage to the chimpanzee/human LCA. After a period of stasis, a further
marked expansion occurred during the past 3 million years in the
terminal descent to modern humans. This last neocortical expansion
resulted from more rapid and prolonged growth of brain mass. Whereas the
chimpanzee brain reaches 40% of its adult size by the end of fetal
life, the modern human brain at birth has reached only 30% of its adult
size (50). Nevertheless, although far from its adult size, the newborn human brain is still larger than the newborn chimpanzee brain (50).
Anthropoid
primates have large brains relative to body size, invasive hemochorial
placentation, and long gestations. During this long gestation, the fetal
brain consumes approximately 65% of the fetal body’s total metabolic
energy (51).
The invasive hemochorial placenta facilitates the transfer of nutrients
from mother to fetus. Among anthropoids, modern humans have the largest
brain, the most invasive placentation, and the longest gestation. In
the earlier ancestry of humans, the threat of destructive maternal
immune attacks on the fetus would have necessitated the evolution of
mechanisms for immune tolerance at the maternal–fetal interface. Genes
that code for galectins, proteins that promote immune cell death, may
have provided the anthropoid fetus with an additional immune tolerance
mechanism for averting maternal immune attacks (52). Anthropoid primates have placental-specific galectins that induce apoptosis of T lymphocytes (52).
These genes originated from gene duplications that occurred in the
anthropoid stem lineage, and then in that lineage, regulatory evolution
of these genes produced placental-specific expression. Moreover, there
was also positive selection for amino acid replacements in the placental
galectins of the common ancestor of anthropoids, of catarrhines, and of
humans. This adaptive evolution contributed to distinctive but not
unique modern human features such as lengthened gestation and increased
brain-to-body size ratio. Paradoxically, because of the selection that
brought about distinctive modern human features, which also include
prolonged postnatal development and longer generation times, we are
genetically closer to the human/chimpanzee LCA than are chimpanzees (27, 32, 35).
Potential
genetic correlates to increased brain size in the primate lineage that
descended to humans is provided by the evolutionary history of Abnormal
Spindle-Like Microcephaly-Associated (ASPM) and microcephalin (MCPH1),
two genes that have mutant forms associated with the severe reduction
of brain size that characterizes microcephaly in humans (53, 54).
During descent of the ape stem portion of the primate lineage to humans
(approximately 25 to 6 Mya), positive selection acted on
microcephalin’s protein-coding sequence, and during the past 6 million
years in descent from the chimpanzee/human LCA to modern humans,
positive selection acted on ASPM’s protein-coding sequence (55⇓⇓⇓–59).
Language
is also considered to be a distinctive human trait. There is evidence
of accelerated evolution in the human terminal of the protein-coding
sequence of Forkhead Box P2 (FOXP2) (60⇓–62). This gene encodes a transcription factor that influences the expression levels of many brain-expressed genes. FOX2P mutants have been found in humans with language dysfunction (63⇓–65), suggesting that adaptive evolution of FOXP2 may have contributed to the origin of modern human spoken language abilities (60, 61).
This adaptive evolution may have occurred in archaic humans ancestral
to both Neanderthals and modern humans, an inference drawn from the
finding that Neanderthal FOXP2 has the same two amino acid replacements
that distinguish modern human FOXP2 from the orthologous chimpanzee
protein (66). The chimpanzee FOXP2 patterns of brain transcriptional regulation differ somewhat from the modern human FOXP2 patterns (67),
although there is no direct evidence that the two amino acid difference
of chimpanzee FOXP2 from modern human FOXP2 causes language
dysfunction. In addition to evidence suggesting FOXP2 has evolved adaptively in humans, five of the genes that FOXP2 regulates had themselves been under positive selection (67). Several genes involved in the development of the auditory system also show evidence of adaptive evolution in modern humans (68).
A
number of recent studies have examined gene expression in the brain
transcriptomes of different primate species. More ex-pression changes
were observed in the human brain than in other primate brains (69). In general, the majority of these changes involved increased expression (70). Among the genes found to be up-regulated in modern humans are genes involved in neuronal activity and metabolic processes (70, 71). Genes involved in oxidative phosphorylation (electron transport) are especially up-regulated in humans (71).
Most recently, Nowick and colleagues suggested that major differences
in expression of brain-expressed genes observed between human and
chimpanzee may be coordinated by a small number of transcription factors
that show differential expression between humans and chimpanzees (72). Interestingly, many of these transcription factors are associated with pathways involved in energy metabolism (72).
In
addition to changes in gene expression level, gene duplication events
during human ancestry may have also contributed significantly to our
brain evolution. All mammals possess a gene that encodes glutamate
dehydrogenase 1 (GLUD1). Whereas GLUD1 is localized to both the
mitochondria and cytoplasm where it functions in the metabolism of
glutamate, a retrotransposon-mediated duplication event in the hominoid
ancestor approximately 18 to 25 Mya (73) resulted in a second GLUD-encoding gene (GLUD2) that is targeted specifically to the mitochondria (74).
Glutamate is the most common neurotransmitter in the brain. It is
believed that positively selected amino acid substitutions in GLUD2 allow for more efficient energy metabolism of glutamate in the brain (74⇓–76).
Aerobic Energy Metabolism Genes and Brain Evolution
Neurons are the most energy-demanding cells of the modern human body (77).
The proliferation and pruning of neurons and their dendrites and the
formation of the synaptic connections involved in learning are all
energy-intensive processes. Thus it was not unexpected that aerobic
energy metabolism (AEM) genes were found to be major targets of positive
selection in the adaptive evolution of enlarged brains. This finding
was made in a phylogenomic study that examined protein-coding sequence
evolution during human ancestry (78).
In the time between the Old World monkey–ape LCA and the
chimpanzee–human LCA, the most favored targets of positive selection
were brain-expressed genes that code for mitochondrial functioning
proteins, e.g., proteins of the oxidative phosphorylation pathway (78, 79). Although not brain-specific, many of these AEM genes are highly expressed in the adult human brain (78).
Moreover, these genes not only show evidence of adaptive evolution on
the lineage to the LCA of humans and chimpanzees, but also on both the
terminal human and terminal chimpanzee lineages. Considering that
mitochondria play an essential central role in the aerobic production of
energy, it may be inferred that the adaptive evolution of AEM genes
improved the molecular machinery that facilitates the functioning of a
high energy–demanding encephalized brain.
Phylogenomic
analysis of approximately 15,000 human coding sequences confirmed that
AEM genes were favored targets of positive selection in the ape stem
period of human ancestry (i.e., between 25 Mya and 6 Mya), with 52 AEM
genes (cellular component GO:0005739; mitochondrion) in the most
enriched cluster of genes showing the signatures of positive selection,
i.e., faster rate of nonsynonymous substitutions (dN) than synonymous
(dS) (79).
In the human terminal lineage (from 6 Mya to present), there were also
many positively selected AEM genes but not significantly more than
expected for any category of genes in the human genome. However, when
these analyses were confined to only those positively selected genes
that also show brain expression levels equivalent to or greater than the
median of all modern human brain–expressed genes (80),
the most enriched clusters in the ape stem and human terminal lineages
consisted of 20 and 23 AEM genes, respectively. Of these brain expressed
AEM genes, 14 and 10 in the ape stem and human terminal lineage,
respectively, were involved in oxidative phosphorylation (Kyoto
Encyclopedia of Genes and Genomes pathway map00190; oxidative
phosphorylation). For more detailed information about these data and the
methods used to infer enrichment for Gene Ontology terms and Kyoto
Encyclopedia of Genes and Genomes pathways, refer to Goodman et al. (79).
If
the evolutionary origins of enlarged hominid brains depended on
adaptively evolved AEM genes, then other large-brained mammals should
also have in their ancestry AEM genes as principal targets of positive
selection. An opportunity to test this hypothesis was provided by the
addition of two afrotherian genomes to the growing set of publically
available sequenced genomes. These two afrotherian genomes are from a
large-brained mammal, the African savanna elephant (Loxodonta africana) and a small-brained mammal, the lesser hedgehog tenrec (Echinops telfairi).
The clade Afrotheria, within which are elephants and tenrecs, is
anciently separated from the clade Euarchontoglires, within which are
humans and mice (Fig. 3A).
Although elephants and tenrecs are phylogenetically closer to each
other than to humans or mice, elephants resemble modern humans by having
such features as large brains, empathetic social bonds, high
intelligence, and prolonged development and long life spans (Fig. 3B; as discussed in ref. 79).
In contrast, tenrecs, as insectivore-grade mammals, have small, poorly
encephalized brains and short life spans. The phylogenomic patterns of
adaptive evolution are more similar between elephant and human than
between either elephant and tenrec lineages or human and mouse lineages,
with adaptively evolved AEM genes being especially well represented in
the elephant and human patterns (Fig. 3C) (79).
In correlation with brain oxygen consumption and brain mass being
largest in elephants and next largest in humans, positively selected AEM
genes were most evident in the elephant lineage (indeed more
overrepresented than any other gene category), next most evident in the
human lineage, and not evident (i.e., not overrepresented) in tenrec and
mouse lineages or in the other examined mammalian pair (the two
laurasiatherians Bos taurus and Canis familiaris).
Fig. 3.
An
example of convergent patterns of adaptive evolution in two
large-brained taxa (elephants and humans). All data presented and images
are adapted from previously published work (79). (A) Species phylogeny based on DNA and fossil evidence (32⇓–34, 84). Lineages of interest are highlighted. (B)
Life history and phenotype variables among study taxa. Values given are
averages. More information and references for these values can be found
in Table S1 of ref. 79. (C) Lineage protein-coding sequence evolution for 501 mitochondria-related genes.
The Human Brain, Different by Degree and Not Kind
Darwin’s
insight that the modern human mind does not differ in kind but rather
in degree from other mammalian minds, in our opinion, should serve as
the main guidepost for pursuing a phylogenomic search for the genetic
roots of the modern human mind. The prospect that high-quality genome
sequences will be obtained from thousands of different mammals (81)
promises to make possible such a phylogenomic search. Key to the search
will be dense representation of the species and genera in each extant
mammalian order. The phylogenetic tree of mammals inferred from genome
sequences can then be used to uncover in each evolved lineage the
genetic changes that had occurred between ancestral and descendent
genomes. Of particular interest will be those adaptive genetic changes
in protein-coding sequences, promoters, and other regulatory sequences.
Phylogenomic
research provides an opportunity to identify those parallel or
convergent patterns of adaptive genetic evolution that correlate with
parallel or convergent patterns of adaptive phenotypic evolution. As an
example, brain size increased in parallel in the stem catarrhines and
stem platyrrhines (82). Encephalization then increased further in ape ancestry, in some Old World monkeys and some New World monkeys (e.g., Cebus) (83).
In addition to humans, a number of primate species also exhibit a great
deal of phenotypic and behavioral plasticity, including chimpanzees,
baboons, macaques, and capuchins. Parallel or convergent patterns of
adaptive genetic evolution among these species might help elucidate
mechanisms contributing to enhanced brain plasticity in modern humans
during childhood when the capacity for learning is greatest.
Nevertheless, the search for genetic correlates of distinctive human
phenotypic features should explore the possibility that some molecular
aspects of modern human brain plasticity might be uniquely human. The
hypothesis could be tested that adaptive evolution in our recent
ancestry increased the diversity of macromolecular specificities
involved in neuronal connectivity and neural plasticity. In testing this
hypothesis, genes such as those concerned with cell–cell interaction,
adhesion, and receptor–ligand binding and their cis-regulatory motifs
should be examined. However, we would not be surprised if phylogenomic
studies reveal that the genetic underpinnings for the basic mechanisms
of brain plasticity are essentially the same as in other catarrhine
primates and that the modern human mind differs from the other species
primarily because of the modern human brain’s larger number of neurons
and dendritic connections and much longer periods of postnatal
development in a social nurturing environment.
A Modern Voyage
With
the advent of large-scale sequencing technologies and new bioinformatic
tools for processing genomic sequence data, we are poised to embark on a
new voyage of exploration and inquiry just as Darwin did in 1831. The
last decade in particular has seen exponential growth in genome sequence
collection and characterization. As we work toward a more complete
understanding of genome structure, biology, and evolution, we become
better able to develop and test hypotheses concerning a number of
fundamental questions in evolutionary biology and human evolution. At
the forefront of our interests are those molecular mechanisms and
adaptations that have resulted in the modern human mind.
Acknowledgments
We
thank Derek Wildman and Larry Grossman for insightful discussion. This
study was supported by National Science Foundation Grants BCS0550209 and
BCS0827546.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: mgoodwayne@aol.com.
- Author contributions: M.G. and K.N.S. designed research; M.G. analyzed data; and M.G. and K.N.S. wrote the paper.
- The authors declare no conflict of interest.
- This article is a PNAS Direct Submission.
- This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “In the Light of Evolution IV: The Human Condition,” held December 10–12, 2009, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. The complete program and audio files of most presentations are available on the NAS Web site at www.nasonline.org/SACKLER_Human_Condition.
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