The Evolutionary Persistence of Genes That Increase Mental Disorders Risk

Author(s): Matthew C. Keller

Source: Current Directions in Psychological Science, Vol. 17, No. 6 (Dec., 2008), pp. 395-399
Published by: Sage Publications, Inc. on behalf of Association for Psychological Science
Stable URL: https://www.jstor.org/stable/20183330
Accessed: 24-03-2025 14:33 UTC

REFERENCES
Linked references are available on JSTOR for this article:
https://www.jstor.org/stable/20183330?seq=1&cid=pdf-reference#references_tab_contents
You may need to log in to JSTOR to access the linked references.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide
range of content in a trusted digital archive. We use information technology and tools to increase productivity and
facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected].

Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at
https://about.jstor.org/terms

Sage Publications, Inc., Association for Psychological Science are collaborating with
JSTOR to digitize, preserve and extend access to Current Directions in Psychological
Science

This content downloaded from 104.51.24.182 on Mon, 24 Mar 2025 14:33:48 UTC
All use subject to https://about.jstor.org/terms
 CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE

The Evolutionary Persistence of

Genes That Increase Mental
Disorders Risk
Matthew C. Keller

Department of Psychology and Institute for Behavioral Genetics, University of Colorado at Boulder

ABSTRACT?Natural selection constantly removes those at a cost to the old tend to spread throughout the population,
genetic variants (al?eles) that even slightly decrease average making anyone, should they live long enough, susceptible to
reproductive success. Yet, given the high heritabilities and diseases of old age.
prevalence rates of severe mental disorders, human popu However, certain human maladies do not fit so easily into the
lations seem to be awash in deleterious al?eles. Evolutionary adaptive framework provided by Darwinian medicine. Perhaps
genetics offers an illuminating framework for understand this is best exemplified by the most severe mental disorders (see
ing why mental disorder risk al?eles have persisted despite Table 1), which seem to be neither defenses, mismatches, nor
natural selection, and this framework can help guide future age-related trade-offs. Unlike diseases that reflect age-related
research in behavioral and psychiatric genetics. trade-offs, the mental disorders in Table 1 tend to strike in childhood
to the early 30s, periods that precede or are coterminous with
KEYWORDS?mental disorders; genetics; evolution; mutation
best estimates of when ancestral humans were reproducing. Nor do
selection; balancing selection; schizophrenia
the mental disorders in Table 1 fit the profiles of diseases primarily
caused by mismatches between ancestral and modern environ
Despite the praise heaped upon the human design by theologians, ments. Diseases caused by such mismatches tend to be highly
philosophers, and evolutionists over the years, several aspects of variable across time and between cultures and should be virtually

it appear decidedly suboptimal. Humans suffer from myriad absent in traditional societies lacking the novel (moderating) envi
ronmental factors. While data on mental disorder rates in the few
seeming design flaws, from fever and vomiting to nearsightedness
and back pain to Alzheimer's and heart disease. The last 30 years remaining traditional societies are lacking and much needed, what

has seen an awakening in our scientific understanding of these evidence we do have implies that the rates of mental disorders in

diseases and susceptibilities?not just in terms of their proximate Table 1 (with the probable exception of autism) are paradoxically
medical causes but also in the deeper sense of why they have high the world over, from the United States to Palau, China to

evolved despite?or because of?natural selection. Botswana, and India to Argentina (e.g., for schizophrenia, see Saha,
Darwinian medicine has made it clear that many such diseases Chant, Welham, & McGrath, 2005).

and susceptibilities are best understood in the context of evolu Finally, the mental disorders listed in Table 1 share little simi

tionary adaptations (Nesse & Williams, 1994). Unpleasant as they larity to known defenses, such as fever and nausea, which are
may be, fever, nausea, diarrhea, and coughing are bodily defenses reliably triggered by environmental threats and which subside

crafted by natural selection to deal with infections and toxins when threats have passed. It is possible that certain reactions, the

(though these symptoms may sometimes be co-opted by pathogens extreme forms of which are deemed mental disorders, represent

for their own selfish ends). Nearsightedness, obesity, and heart adaptive defenses. For example, Keller and Nesse (2006) hypoth
disease probably reflect mismatches between the environments our esized that normal depressive reactions?the types that most
bodies evolved to deal with and modern ones that pose novel people experience following deaths, failures, and so forth?serve

challenges. Age-related diseases such as Alzheimer's likely reflect specific adaptive functions in the situations that arouse them,

the fact that genes with "antagonistic" effects that benefit the young much as other unpleasant defenses such as normal fever or pain
serve situation-specific functions. Persistent depressive reactions
(clinical depression) may represent either extreme/intractable
Address correspondence to Matthew C. Keller, Department of Psy
chology, Muenzinger Hall, 345 UCB, Boulder, CO, 80309; e-mail: situations (perhaps more common in modern environments) or
matthew. c. keller @gmail. com. dysregulated neurological systems (which may have strong genetic

Volume 17?Number 6 Copyright ? 2008 Association for Psychological Science 395

This content downloaded from 104.51.24.182 on Mon, 24 Mar 2025 14:33:48 UTC
All use subject to https://about.jstor.org/terms
 Evolution, Genetics, and Mental Disorders

TABLE 1
Genetic Basis, Fitness Effects, and Prevalence Rates of a Small Subset of Single-Locus Disorders and Severe Mental Disorders

Modern fertility Lifetime prevalence

Disorder Genetic basis estimates per 100,000 in U.S.

Disorders caused by mutations at a single locus

Platyspondylic skeletal dysplasia Dominant mutations at 12ql3 unknown (very low) <1
Granulomatous disease Type I Recessive mutations at 7qll.23 unknown (low) <1
Apert's syndrome Dominant mutations at 10q26 unknown (very low) 1.5
Achondroplastic dwarfism Dominant mutations at 4q unknown (low) 2-4
Severe mental disorders
Autism unknown; h = .90 unknown 200 (variable)
Bipolar disorder unknown; h2 2* .60 63% (2 studies) 800
Schizophrenia unknown; h2 9? .80 47% (12 studies) 800
Mental retardation unknown; h = .65 80% (3 studies) 2,000

Note. Genetic basis and prevalence estimates obtained from Online Mendelian Inheritance in Man (n.d.) for single-locus disorders and from the National Institute
of Mental Health (1998) for severe mental disorders. Modern fertility estimates are the average fertility estimates (percentage of those with the disorders compared
to control samples) from all available studies from 1960 to 2005. Shown in parentheses are the numbers of studies on which estimates are based (for severe mental
disorders) or the subjective judgments of these estimates (for single-locus disorders), h = heritability estimate.

underpinnings, requiring an evolutionary explanation for why such et al., 2005). Moreover, mental disorders account for nearly two
genes exist; see below). However, the mental disorders in Table 1 thirds of the total disease burden among reproductively aged
are not reliably triggered by environmental factors, and they tend persons, and almost every investigation on the topic has found that
to persist, often for life, rather than to subside. Moreover, whereas the severest of them are associated with profound social impair
virtually everyone has the capacity to have a fever or feel sad ments and reductions in reproductive success (Table 1).
given the "right" situation, it is very unlikely that more than a small Why were the al?eles that predispose to severe mental disor
minority of people have the capacity to develop autism or schizo ders (hereafter, risk al?eles) not purged long ago by natural
phrenia, for example, no matter what their circumstances. selection? If, over all the environments and all the genomes an
In short, the adaptive explanations that elucidate many other al?ele finds itself in, it has an even slightly negative or positive
seeming human design flaws fail when it comes to severe mental effect, it will either go extinct or reach fixation, respectively?
disorders. At its core, this is because traditional Darwinian and will confer no heritability to traits. This happens surpris
medicine explanations explain universal adaptive capacities, ingly rapidly, within tens to hundreds of generations for even
not heritable differences in risk. small positive or negative fitness effects. So the paradox boils
down to this: Why do seemingly detrimental (but the paradox is
THE EVOLUTIONARY PARADOX OF SEVERE every bit as salient if they are beneficial) risk al?eles hang around
MENTAL DISORDERS at intermediate frequencies, where they confer heritability to
mental disorders? Some simple resolutions to this paradox?that
One of the most robust findings in modern psychiatric research ancestral humans reproduced earlier than modern ones do, that
has been that common, severe mental disorders are moderately risk al?eles are strongly epistatic (moderated by other al?eles)
to highly heritable (Table 1), meaning that differences in genetic
and hidden from selection, that mental disorders were benign
variants (al?eles) between people cause differences in risk. From ancestrally?do not hold up well to theoretical and empirical
an evolutionary perspective, this heritability and commonality scrutiny (reviewed in Keller & Miller, 2006). Three mechanisms
poses a paradox. Natural selection constantly removes from the better grounded in modern evolutionary genetics?each of
population al?eles that tend to decrease, even imperceptibly, which leaves different, albeit messy, signatures in the genome?
their carriers' fitness (expected number of surviving offspring). are reviewed below.
Therefore, one might expect heritable disorders either to be rare
or else not truly harmful to fitness. Yet severe mental disorders POTENTIAL RESOLUTIONS TO THE PARADOX
are puzzlingly common from an evolutionary perspective, being
hundreds and even thousands of times more prevalent than the Mutation-Selection
2,000 or so single-locus diseases known to harm fitness (Table 1). Mutations are copying errors that occur during DNA replication.
Severe mental disorders have a cumulative prevalence of some These can be substitutions of a single base pair (point mutations)
6% in the United States (Kessler, Chiu, Dernier, & Walters, or deletions, duplications, inversions, or translocations of many
2005), and nearly 50% of people meet criteria for a less severe base pairs in a row. Of evolutionary relevance are those mutations
mental disorder such as depression during their lifetimes (Kessler that occur when sperm or egg cells are created. These mutations

396 Volume 17?Number 6

This content downloaded from 104.51.24.182 on Mon, 24 Mar 2025 14:33:48 UTC
All use subject to https://about.jstor.org/terms
 Matthew C. Keller

can be passed on to fertilized ova. If so, they will be copied into others too anxious or not anxious enough, and so forth. But some
every cell in the offsprings body, including the offspring's people inherit an especially high "load" of mutations (from hun
own sperm or egg cells and thus potentially transferred to any dreds of small-effect ones to a single large-effect one) that disrupt
descendant thereafter. This is how new mutations are "introduced" particular neurodevelopmental pathways, increasing the risk
into a population. Very rarely, through blind luck, new mutations of aberrant behaviors and psychiatric categorization. According
happen to increase their carriers' average reproductive success, to mutational models, mental disorders are not "natural kinds"
and over time can spread through a population, forming the genetic with clear boundaries and common causes, but rather are umbrella

basis of new, universal adaptations. Almost always, however, concepts covering a heterogeneous group of similar-appearing
mutations that affect organic machinery degrade rather than phenotypes.
improve its tightly coordinated performance. The empirical evidence that mutations play at least some role
Mutation-selection models describe the equilibrium between in the etiology of severe mental disorders is compelling (Table 2).
new mutations being introduced into the population and their Also telling is what has not been found. Despite 20 years of gene
removal, usually many generations later, by natural selection. hunting, scientists have not found clear links between specific
Across individuals at a given time, a gene harbors one or a few al?eles and severe mental disorders, which might suggest that
functionally equivalent "normal" allele(s) at a very high frequency many different risk al?eles exist, no one of which accounts for
and many different rare, deleterious mutations. While each indi much population risk?exactly what would be predicted from a
vidual deleterious mutation is destined for eventual extinction, mutational model. However, methods to find risk al?eles to date

new ones are constantly arising, creating an equilibrium in the have been less than optimal. The next 5 years, when results from
population between normal al?eles (which most people have at a a large number of whole-genome association studies will be
given gene) and rare, deleterious mutations (which a tiny minority released, will clarify whether many different, individually rare
of people have at that gene). These mutations create maladaptive al?eles (consistent with mutation-selection balance) or a handful
noise?and heritability?in traits. of individually common al?eles (consistent with either of the
After years of being discounted as a major force, many evolu evolutionary processes reviewed next) are the most important in
tionary geneticists now consider mutation selection to be the explaining the heritability of mental disorders.
principal factor explaining the heritability of complex traits (Houle,
1998). The key insight was to realize that although mutations are
rare per gene, hundreds or even many thousands of genes can in Evolutionary Time Lags
fluence complex traits, and so the cumulative number of mutations Mutation-selection is unlikely to be the sole explanation for the
affecting such traits could be high enough to explain their herita heritability of severe mental disorders, nor is it inconsistent with
bility. This insight has, in turn, been used as a basis for resolving the other processes. One class of explanation that may be particu
paradox of common, heritable mental disorders (Gangestad & Yeo, larly important is evolutionary time lags. When environments
1997; Keller & Miller, 2006; McClellan, Susser, & King, 2007). change quickly, as many aspects of human environments have,
Supporting this view are findings indicating that the number of there can be mismatches such that ancestral al?eles are poorly
genes harboring deleterious mutations is quite large: Proper adapted to current environments. Given the increasing aware
cellular functioning is disrupted by the action of some 500 old, ness that allelic effects can depend on the environmental context
slightly deleterious mutations passed down from great, great... (Moffitt, Caspi, & Rutter, 2005), al?eles that were once neutral or
grandparents (Fay, Wyckoff, & Wu, 2001) as well as one or two adaptive may be today's risk al?eles.
new deleterious mutations that arose for the first time in the The ancestral-susceptibility model (Di Rienzo & Hudson,
parent's egg or sperm cells (Eyre-Walker & Keightley, 1999). Of 2005) proposes that many current risk al?eles are ancestral and
course, these are just averages; some people inherit many more are being driven to extinction due to rapid changes in human
mutations than average and some many fewer, and mutations environments. Consistent with this, rates of allelic substitution
vary enormously in their effect sizes, creating individual (reflecting natural selection) are over 100 times higher in the last
differences in the degree to which organs (including the brain) 10,000 years than they were during most of human evolution
are disrupted by them. The phenotypic effects of these mutations (Hawks, Wang, Cochran, Harpending, & Moyzis, 2007). Several
range from the drastic and tell-tale, causing the single-gene risk al?eles for common diseases, such as Alzheimer's and
disorders so successfully mapped by geneticists, to individually hypertension, are ancestral (Di Rienzo & Hudson, 2005), and Lo
small, unnoticeable ones, which tend to be more common because et al. (2007) found that schizophrenia risk al?eles in the GABA
they are removed more slowly by selection. A receptor ?2 gene have been under recent negative selection.
The variation in the cumulative effect of mutations might serve Another type of time-lag explanation involves the coevolution
as an important substrate to the heritability of mental disorders. between pathogens and their hosts (Gangestad & Yeo, 1997).
By this view, mutations that degrade the brain's performance Pathogens rapidly evolve new adaptations to better thrive in
differentiate everyone on a panoply of behavioral dimensions, human bodies. This causes many different defense al?eles?some
making some people slow at learning, others bad at remembering, better than others?to exist in the population at a given time.

Volumel7?Number 6 397

This content downloaded from 104.51.24.182 on Mon, 24 Mar 2025 14:33:48 UTC
All use subject to https://about.jstor.org/terms
 Evolution, Genetics, and Mental Disorders

TABLE 2
Strength of Various Lines of Evidence Consistent With a Mutational Role in the Risk of Four Mental Disorders

Evidence Interpretation SZ MR BD AU
Indirect Methods
Low modern fitness Traits whose genetic variation is maintained by mutation-selection
should demonstrate low fitness, although modern and ancestral fitness
have unknown relationships.
Brain trauma Major phenotypic disruptions increasing mental-disorder risk is consistent
with the hypothesis that genetic disruptions (mutations) can do likewise.
Paternal age effects New mutations accumulate in sex (sperm/egg) cells as males (but not as
females) age.
Known parental Natural selection weeds out deleterious mutations with dominant or additive
inbreeding effects, leaving extant deleterious mutations skewed toward recessivity;
by increasing homozygosity, inbreeding reveals their full harmful effects.
Direct (molecular) methods
Chromosomal These can be considered mutations of large effect, affecting multiple genes at
** ***
abnormalities once, causing more pronounced phenotypic effects than point mutations
and making them easier to detect in pedigrees.
Rare deletions and Like new or rare point mutations, new or rare deletions and duplications are
duplications likely to be deleterious to fitness.

Note. Numbers of stars (0 to 3) represent the author's appraisal of strength of evidence for various lines of evidence for mutation-selection maintaining the genetic
variation in schizophrenia (SZ), mental retardation (MR), bipolar disorder (BD), and autism (AU). It is unknown whether a paucity of evidence reflects null and
unreported findings or little investigation. For technical reasons, it is not yet possible to directly assess the impact of point mutations, but this is not the case for
deletions and duplications.

Pathogens, which can affect neurodevelopment, are known risk Although balancing selection has been a favored explanation
factors for several mental disorders. For example, several studies for the persistence of risk al?eles, my own view is that its popu
have found that childhood Streptococcal infections are weakly larity outstrips its support. One type of evidence for balancing
associated with adult obsessive-compulsive disorder (Kim et al., selection would come from finding high-frequency al?eles?
2004). If resistance to Streptococcal infections is heritable, then a prediction from practically every model of balancing selec
part of the heritability of obsessive-compulsive disorder could be tion?that affect mental disorder risk. Gene-mapping studies
due to Streptococcal-human coevolution. This example illustrates have not had much success yet matching specific al?eles to
that the risk al?eles responsible for the heritability of mental dis severe mental disorders, however, which suggests (but does not
orders need not directly increase mental-disorder risk. Rather, prove) that such risk al?eles are individually rare rather than
they may make one vulnerable to factors such as pathogens that common. Moreover, a recent whole-genome scan designed to
do increase risk. detect signatures of ancient balancing selection in humans
discovered no loci under balancing selection apart from those
few already known to exist (Bubb et al., 2006).
Balancing Selection Another type of evidence consistent with the balancing-selection
Balancing selection occurs when natural selection actively hypothesis would be finding that relatives of those with mental
maintains two or more equally fit al?eles at a gene. This usually disorders have some sort of fitness advantage. This might suggest
occurs because the fitness of the al?eles increases as they become that low doses of risk al?eles (typically found in relatives) have
rarer: If one al?ele drifts to a lower frequency than its equilibrium positive effects that counterbalance their high-dose negative
value, its fitness increases, which then nudges its frequency back effects. Several studies on schizophrenia have looked at this issue,
toward the equilibrium. H?t?rozygote advantage?in which indi and although mixed, the weight of evidence indicates that relatives
viduals who are h?t?rozygote {Ad) at a gene have higher fitness than of schizophrenics have equal or lower fitness than average, not
those with either homozygote (A4 or aa)?is a special case of this higher fitness as required by balancing-selection arguments (Keller,
process. For example, individuals in equatorial Africa who are 2008). Nevertheless, modern reproductive success may correlate
heterozygous at the ?-hemoglobin locus are protected against poorly with ancestral reproductive success. More intriguing support
malaria, whereas homozygous individuals are either vulnerable to comes from studies showing that schizotypy (a personality dimen
malaria or at risk of sickle-cell anemia. Each al?ele?as well as sion, the extreme of which may constitute schizophrenia) is higher
sickle-cell anemia?is maintained in equatorial Africa because if among highly creative individuals (Nettle & Clegg, 2006). One
one al?ele becomes infrequent by chance, it more often finds itself interpretation is that low doses of schizophrenia risk al?eles
paired with the opposite al?ele, increasing its fitness and frequency. increased creativity and fitness in ancestral environments.

398 Volume 17?Number 6

This content downloaded from 104.51.24.182 on Mon, 24 Mar 2025 14:33:48 UTC
All use subject to https://about.jstor.org/terms
 Matthew C. Keller

CONCLUSIONS Gangestad, S.W., & Yeo, R.W. (1997). Behavioral genetic variation,
adaptation and maladaptation: An evolutionary perspective.
Trends in Cognitive Sciences, 1, 103-108.
Why do the al?eles that predispose to severe mental disorders
Hawks, J., Wang, E.T., Cochran, G.M., Harpending, H.C., & Moyzis,
exist? We don't yet know, but mutation selection, time lags, and
R.K. (2007). Recent acceleration of human adaptive evolution.
balancing selection probably all play roles to different degrees.
Proceedings of the National Academy of Sciences, USA, 104,
My own view is that mutation-selection explanations enjoy the 20753-20758.
strongest support to date, but the weight of evidence may shift as Houle, D. (1998). How should we explain variation in the genetic
new data become available. Given the rapidity with which the variance of traits? Gen?tica, 102, 241-253.

genetic code is being deciphered and the increasing ability to Keller, M.C. (2008). Problems with the imprinting hypothesis of schizo

test evolutionary hypotheses using genetic data, it is likely that,

phrenia [commentary]. Behavioral and Brain Sciences, 31,
273-274.
within the next 10 to 20 years, we will have a good understanding
Keller, M.C, & Miller, G. (2006). Resolving the paradox of common,
of why the al?eles that increase risk for severe mental disorders
harmful, heritable mental disorders: Which evolutionary genetic
have persisted over evolutionary time. Stay tuned. models work best? Behavioral and Brain Sciences, 29, 385-452.
Keller, M.C, & Nesse, R.M. (2006). The evolutionary significance of
depressive symptoms: Different adverse situations lead to different
Recommended Reading depressive symptoms patterns. Journal of Personality and Social
Barton, N.H., & Keightley, P.D. (2002). Understanding quantitative Psychology, 91, 316-330.
genetic variation. Nature Reviews Genetics, 3,11?21. A very good, Kessler, R.C, Chiu, W.T., Dernier, 0., & Walters, E.E. (2005). Preva
accessible review of how evolutionary geneticists explain herita lence, severity, and comorbidity of 12-month DSM-IV disorders in
bility in traits. the National Comorbidity Survey Replication. Archives of General
Gangestad, S.W., & Yeo, R.W. (1997). Behavioral genetic variation, Psychiatry, 62, 617-627.
adaptation and maladaptation: An evolutionary perspective. Kim, S.W., Grant, J.E., Kim, S.I., Swanson, T.A., Bernstein, G.A.,
Trends in Cognitive Sciences, 1, 103-108. An early paper intro Jaszcz, W.B., et al. (2004). A possible association of recurrent
ducing the mutation-selection view of mental disorder risk. streptococcal infections and acute onset of obsessive-compulsive
Keller, M.C., & Miller, G. (2006). Resolving the paradox of common, disorder. Journal of Neuropsychiatry and Clinical Neuroscience,
harmful, heritable mental disorders: Which evolutionary genetic 16, 252-260.
models work best? Behavioral and Brain Sciences, 29,385-452. A Lo, WS., Xu, Z, Yu, Z, Pun, F.W, Ng, S.K., Chen, J, et al. (2007). Positive
thorough overview of the topics in this article, including critical selection within the schizophrenia-associated GABA(A) receptor
commentaries. beta2 gene. PLoS ONE, 2, e462.
Mealey, L. (1995). The sociobiology of sociopathy: An integrated evolu McClellan, J.M, Susser, E, & King, M.C (2007). Schizophrenia: A
tionary model. Behavioral and Brain Sciences, 18, 523-599. A common disease caused by multiple rare al?eles. British Journal of
well-reasoned paper arguing that balancing selection has main Psychiatry, 190, 194-199.
tained sociopathy. Moffitt, T.E, Caspi, A, & Rutter, M. (2005). Strategy for investigating
Nesse, R.M., & Williams, G.C. (1994). Why we get sick: The new science interactions between measured genes and measured environ
of Darwinian medicine. New York: Times Books. A user-friendly ments. Archives of General Psychiatry, 62, 473-481.
book that introduced Darwinian medicine to the mainstream. National Institute of Mental Health. (1998). Genetics and Mental Disorders:
Report of the National Institute of Mental Healths Genetic Workgroup
(NIH Publication No. 98-4268). Bethesda, MD: Author.
REFERENCES Nesse, R.M, & Williams, G.C. (1994). Why we get sick: The new science
of Darwinian medicine. New York: Times Books.
Bubb, K.L., Bovee, D., Buckley, D., Haugen, E., Kibukawa, M., Paddock, Nettle, D, & Clegg, H. (2006). Schizotypy, creativity and mating suc
M., et al. (2006). Scan of human genome reveals no new Loci under cess in humans. Proceedings of the Royal Society of London, Series
ancient balancing selection. Genetics, 173, 2165-2177. B, 273, 611-615.
Di Rienzo, A., & Hudson, R.R. (2005). An evolutionary framework for Online Mendelian Inheritance in Man. (n.d.). Baltimore, MD: McKusick
common diseases: The ancestral-susceptibility model. Trends in Nathans Institute of Genetic Medicine, Johns Hopkins University;
Genetics, 21, 596-601. and Bethesda, MD: National Center for Biotechnology Information,
Eyre-Walker, A., & Keightley, P.D. (1999). High genomic deleterious National Library of Medicine. Retrieved October 13, 2007, from
mutation rates in hominids. Nature, 397, 344-347. http://www.ncbi.nlm.nih.gov/omim/

Fay, J.C., Wyckoff, G.J., & Wu, C. (2001). Positive and negative selection Saha, S, Chant, D, Welham, J, & McGrath, J. (2005). A systematic review
on the human genome. Genetics, 158, 1227-1234. of the prevalence of schizophrenia. PLoS Medicine, 2, 413-433.

Volume 17?Number 6 399

This content downloaded from 104.51.24.182 on Mon, 24 Mar 2025 14:33:48 UTC
All use subject to https://about.jstor.org/terms