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Proc Natl Acad Sci U S A. 2001 May 22; 98(11): 6233–6240. doi: 10.1073/pnas.101109298. | PMCID: PMC33451 |
Copyright © 2001, The National Academy of Sciences Evolution Evolution of genome–phenome diversity under
environmental stress Eviatar Nevo* Institute of Evolution, University of Haifa, Haifa 31905, Israel Accepted March 5, 2001. The genomic era revolutionized evolutionary biology. The enigma of
genotypic-phenotypic diversity and biodiversity evolution of genes,
genomes, phenomes, and biomes, reviewed here, was central in the
research program of the Institute of Evolution, University of Haifa,
since 1975. We explored the following questions. (i) How
much of the genomic and phenomic diversity in nature is adaptive and
processed by natural selection? (ii) What is the origin
and evolution of adaptation and speciation processes under
spatiotemporal variables and stressful macrogeographic and
microgeographic environments? We advanced ecological genetics into
ecological genomics and analyzed globally ecological, demographic, and
life history variables in 1,200 diverse species across life, thousands
of populations, and tens of thousands of individuals tested mostly for
allozyme and partly for DNA diversity. Likewise, we tested thermal,
chemical, climatic, and biotic stresses in several model organisms.
Recently, we introduced genetic maps and quantitative trait loci to
elucidate the genetic basis of adaptation and speciation. The
genome–phenome holistic model was deciphered by the global regressive,
progressive, and convergent evolution of subterranean mammals. Our
results indicate abundant genotypic and phenotypic diversity in nature.
The organization and evolution of molecular and organismal diversity in
nature at global, regional, and local scales are nonrandom and
structured; display regularities across life; and are positively
correlated with, and partly predictable by, abiotic and biotic
environmental heterogeneity and stress. Biodiversity evolution, even in
small isolated populations, is primarily driven by natural selection,
including diversifying, balancing, cyclical, and purifying selective
regimes, interacting with, but ultimately overriding, the effects of
mutation, migration, and stochasticity. Ecological Genomics: Extension of Ecological Genetics Long-Term Research Program in the Institute of
Evolution. The genomic revolution has
dramatically opened wide horizons for evolutionary studies, linking
molecular and organismal organizational levels. Here, I primarily
review the 1975–2000 research program in the Institute of Evolution,
University of Haifa. This program involves biodiversity evolution, from
bacteria to mammals, of genes, genomes, phenomes, populations,
species, ecosystems, and biota as well as their intimate reciprocal
interaction with spatiotemporal variables and the stressful physical
and biotic environments resulting in adaptation and speciation. Our model organisms represent diverse taxa across life, from bacteria
to mammals, in an attempt to unravel regularity, convergence, and
divergence of genotypic and phenotypic patterns: Nostoc
linckia (cyanobacterium); Sordaria fimicola
(coprophilous fungus); Triticum dicoccoides and
Hordeum spontaneum (wild cereals); Drosophila
melanogaster (fruit fly); Spalax ehrenbergi
superspecies (blind subterranean mole rats); Acomys
cahirinus and Apodemus mystacinus (aboveground
rodents). We also studied globally and regionally the population
genetics of 1,200 species from bacteria to mammals, primarily based on
literature data and species richness of 3,000 species in the two
“evolution canyons” (ECs). The aforementioned model organisms comprise haploids and diploids,
inbreeders and outbreeders, as well as sedentary and migratory
organisms. Our ecological theaters include global (the entire planet),
regional (Israel and the Near East Fertile Crescent), and local
(several microsites in the Galilee Mountains Neve-Yaar, Yehudiyya,
Tabigha, and Ammiad) studies, and the model system in the Carmel and
Galilee Mountains. The environmental stresses analyzed include thermal, chemical,
climatic, and biotic, studied in the field and under critical
laboratory conditions. The biological systems include phenotypes
(morphological, physiological, and behavioral) and genotypes (proteins
and DNA, coding and noncoding levels). We have attempted a holistic,
integrative analysis of the organism–environment interaction in the
twin evolutionary processes of adaptation and speciation. Major problems of evolutionary biology await solutions. They can
be resolved in a genomic era, when complete prokaryote and eukaryote
genomes are available for comparative analysis ( 1). A major unresolved
question is how much of the coding and noncoding genome diversity, the
latter comprising >95% in eukaryotes, affects the twin evolutionary
processes of adaptation and speciation. Furthermore, how much of this
diversity in coding and particularly noncoding genomes, often called
“junk” DNA, contributes to regulation and differential fitness of
organisms and is subjected to natural selection? What proportion of
observed genic and nongenic diversity is maintained by selection? How
much of the diversity in noncoding DNA is adaptive and regulates gene
expression, transcription, translation, recombination, and repair? The
adaptive nature of the noncoding genome now turns out to be one of the
most intriguing questions in evolutionary genetics, as was the case
with the coding genome during the last decades of the 20th century. Methods and Ecological Testing Theaters. To answer the problems of diversity in the coding and noncoding genome,
it is not sufficient to measure their genetic diversity. The estimates
of molecular diversity derived from PCR-based techniques—such as
amplified fragment length polymorphism (AFLP), microsatellites (short
sequence repeats or SSR), single nucleotide polymorphism (SNP) and
sequence comparisons—are several-fold higher than enzymatic diversity.
The elucidation and significance of molecular diversity need critical
examination, experiments, and mapping that relate to coded allozymes
but particularly to noncoding DNA diversity and to explanatory attempts
of DNA linguistics (ref. 2; V. M. Kirzhner, A. B. Korol, A.
Bolshoy, and E.N., unpublished work). Essentially, we are attempting to elucidate the reciprocal
relationships between organism and environment. This strategy has been
adopted by the school of ecological genetics ( 4). This strategy guiding
the research program of the Institute of Evolution (1975–2000) across
life and diverse ecogeographical theaters, coupled with observations
and critical experiments, proved successful at global ( 5), regional
( 6), and local ( 7, 8) scales (reviewed in refs. 9– 12) at the allozyme
diversity level. The strategy has now been extended into the DNA coding
and noncoding genomes, thereby advancing the science of ecological
genomics. The major questions for allozymes, and now for the DNA coding
and noncoding genome, relate to the organism–environment interaction.
Is the diversity random or nonrandom? How does differential stress and
niche-width affect genomic and phenomic diversity? What are the
genome–phenome relationships? Does speciation necessarily entail large
genomic changes? Allozyme Diversity and Evolution. Darwin introduced natural selection as the major mechanism of
evolution. But what proportion of all genomic and phenomic evolutionary
change results from natural selection? The most striking
population-genetic feature is the great and widespread allozyme
diversity in nature across unrelated organisms from bacteria to mammals
( 9– 12, 16– 18). Can the study of origin and dynamics of genotypic and
phenotypic diversity, within and between populations, demonstrate that
natural selection is indeed the mechanism underlying the genetic and
organismal basis of evolutionary change? What is the proportion of adaptive coding genetic diversity in nature?
Does most genetic diversity originate by random transitory lethal
mutations constantly removed by purifying directional selection, as
proposed by the neutral theory of molecular evolution ( 13) accentuating
the Wrightian idea ( 14) of random genetic drift in small populations?
Are most genetic polymorphisms neutral, linked (that is,
“hitchhiked”) to only a few selected loci across the genome? Or,
by contrast, does spatiotemporal balancing natural selection maintain
diversity within populations and diversify it between populations,
thereby causing adaptive evolution and speciation ( 9– 12, 16– 18)? Or
is the theory of nearly-neutral alleles ( 19) the satisfactory solution? These questions remained largely controversial in the classical review
of Lewontin ( 15). Our evidence (reviewed in refs. 5– 12) and that of
others ( 16– 18) suggest that most isozyme and allozyme diversity in
natural populations is apparently maintained by some kind of natural
selection. The observation of significant linkage disequilibrium within
and between populations reinforces the importance of natural selection
in the maintenance of genetic polymorphisms in nature, at single,
double, and multilocus structures. Does the adaptive nature of the
large proportion of allozyme polymorphisms represent only small genome
fractions, or is it relevant to the >95% of the noncoding genome?
This question now becomes a major, still largely unresolved issue of
biological evolutionary theory. I first briefly review the allozymic
evidence, before focusing on the current debate about the noncoding
genome, still called unjustifiably by many “junk” DNA, divided
into regulatory and random regions. Allozymic Diversity Patterns at Global, Regional, and Local
Geographic Scales. We analyzed 1,200 species, thousands of populations, and tens of
thousands of individuals for allozymic diversity encoded by 20–50
enzymatic loci in three natural genetic laboratories: (i)
global, across the planet (1,100 species); (ii) regional,
Near East (33 species) and Israel (38 species); and (iii)
local, four microsites in Israel (29 species). Genetic diversity varied by different degrees between and within the
numerous species tested at both the protein and DNA levels. Genetic
organization in nature, at all descending scales, global, regional, and
local, is nonrandom and heavily structured. Genetic organization
frequently displays parallel and repetitive trends in unrelated taxa,
positively correlated with, and predictable by, abiotic and biotic
ecological heterogeneity (that is, spatiotemporal variation in
niche-width) and environmental stress, and is often negatively
correlated with population size ( 11). These results are inconsistent
with the predictions of the neutral theory of molecular evolution ( 13)
and seem to be primarily driven by natural selection. Critical
laboratory experiments with marine organisms subjected to pollution
cause fast differential mortality of allozyme genotypes, indicating
that they are selected by the environment ( 20). The Adaptive Evolution of Enzyme Kinetic Diversity. Kinetic studies of hemoglobin, haptoglobin, transferrin proteins, and
at least a dozen enzyme polymorphisms typically reveal biochemical
kinetic differences among the gene products of alternative genotypes at
a locus ( 16). These include single gene effects, such as lactate
dehydrogenase in killifish, leucine aminopeptidase in blue mussel, and
phosphoglucose isomerase in Collias butterflies. Similar
results were obtained with alcohol dehydrogenase in fruit flies,
salamanders, and barley; glutamate-pyruvate transaminase in copepods;
as well as esterase, glucose-6-phosphate, 6-phosphogluconate
dehydrogenase, and superoxide dismutase in fruit flies ( 16). In all
these cases, biochemical-kinetic studies reveal differences among
phenotypes, either within or across species, that have measurable
effects of alternative genotypes on the physiology of whole
individuals. These genotypes result in differential fitness
distinguished by natural selection in keeping with their alternative
spatiotemporal environments ( 16). Genome and Phenome Evolution of Subterranean Mammals at Global,
Regional, and Local Scales. I exemplify genome and phenome evolution in one of nature's best
studied long-term (about 45 million years old), global evolutionary
experiment of mammals adapting to life underground (see figure 2.1 in
ref. 21). The global adaptive convergence of subterranean mammals
currently involves three orders: rodents, insectivores, and marsupials,
which include 11 families, 50 genera, and several hundreds of species.
This global evolutionary process followed the stepwise climatic cooling
and drought, which in turn was followed by biotic extinction in the
transition from the middle Eocene to the early Oligocene. This period
witnessed 10 million years (45–35 Ma = million years ago) of
profound change in earth's geology, climate, and biota. The earth
changed from the Mesozoic “hot house”—i.e., from a warm,
equable, mostly subtropical world that persisted from the Mesozoic to
the early Cenozoic—to the Neogene (Miocene to present) “cold
house.” The ecological theater of open country biotas that opened up
progressively in the Cenozoic, following the Eocene–Oligocene
transition, was associated with increasing aridity, colder climate, and
terrestrialism. This climatic change set the stage for a rapid
evolutionary play of recurrent Neogene adaptive radiations of unrelated
mammals on all continents into the subterranean ecotope. Subterranean Ecotope. The subterranean ecotope is relatively simple, stable, specialized, low
or medium in productivity, predictable, and discontinuous. Its major
evolutionary determinants are specialization, competition, and
isolation ( 21). This ecotope involves the herbivorous (rodents) and
insectivorous (insectivores and marsupials) niches. All subterranean
mammals share molecular and organismal convergent adaptations to their
common unique ecology. By contrast, they display divergent adaptations
to their separated niches of herbivory and insectivory and to their
different phylogenies. The remarkable adaptive evolution of
subterranean mammals involves structural and functional regression and
progression changes caused by colonizing the underground ecotope. It is
a triumphant example of the comparative method in evolutionary biology
demonstrating global convergent evolution caused by similar underground
ecological constraints and stresses at both the molecular and
organismal levels, causing distant organisms to converge adaptively
( 21). Adaptationist Program. The evidence derived from the global convergence of subterranean
mammals ( 21) and regional divergence ( 22, 23) corroborates evolutionary
theory. Convergent evolution and adaptations to life underground
remarkably substantiate a critical adaptationist program, which is the
only viable program to explain biological evolution. No alternative
model can explain the evolution of subterranean mammals with the
stresses of life underground. The descriptive evidence and analytical
results across subterranean mammals indicate a massive global genotypic
and phenotypic convergence. The adaptive mosaic evolution of the
Spalax eye presents an outstanding example of coupled
regression (reduction) and progression (expansion) caused by molecular
and organismal selective evolutionary tinkering underground.
Remarkably, the genetic basis of eyes and brains seems to be
conservative across the animal kingdom, generated by Pax-6
homologues and a cascade of homeotic genes. Similar morphological,
physiological, and behavioral adaptive regressions and progressions are
demonstrated by the auditory system and the massive brain
reorganization. Notably, both the cerebellum, underlying digging, and
the neocortex, underlying the extensive, unique physiology and behavior
of subterranean mammals, relate to brain reorganization through
neuroanatomical evolutionary tinkering ( 21). Allozymic Diversity. The controversy about allozyme heterozygosity in subterranean mammals
was first reviewed across 243 small mammals (111 aboveground and 132
subterranean); the conclusion was that subterranean mammals are indeed
less heterozygous presumably because of the relatively narrow
microclimatic niche underground ( 21). This conclusion is supported by a
broader perspective at global, regional, and local scales in more than
1,200 species analyzed allozymically at the interface between genetics
and ecology ( 11). The levels of genetic diversity in nature, including
the narrow niche subterranean ecotope, are positively correlated with
niche-width and often negatively correlated with effective population
size, negating neutrality and substantiating selection as the best
explanatory mechanism responsible for both the protein and DNA levels
of molecular evolution. This phenomenon holds true in subterranean
mammals and elsewhere ( 11). Microgeographic Critical Tests in Nature Microsite ecological contrasts are excellent critical tests for
evaluating the dynamics of genome and phenome evolution and assessing
the relative importance for adaptation and speciation of the
evolutionary forces causing differentiation ( 7, 8). The latter involve
mutation (in the broadest sense, including recombination), migration,
chance, and selection. At a microsite, mutation, which is usually
considered a clockwise neutral process, is expected to be similar
across the microsite. Migration, which operates for any organism at the
microsite, even sessile organisms, is expected to homogenize allele
frequencies. Stochasticity is not expected to result in repetitive,
ecologically correlated patterns. Selection seems to be the only
evolutionary force expected to result in repeated ecologically
correlated patterns ( 5). In 1977, at the Institute of Evolution, we embarked on a series of
microsite studies comparing sharply contrasting ecological alternative
patterns of temperatures (cold vs. hot in balanids, sessile
crustaceans; e.g., ref. 24); aridity index (high vs. low in wild
cereals; e.g., refs. 8, 11, 25, and 31); lithology (igneous, volcanic,
and sedimentary rocks; e.g., refs. 26, 31, and 32); soil types (terra
rossa, rendzina, and basalt in wild cereals; e.g., refs. 26, 31, and
32); topography ( 27); and chemical [nonpolluted vs. polluted
environments with inorganic heavy metals (Hg, Cd, Zn, Pb, Fe) and
organic (detergents and oil) pollutants in marine organisms; e.g., ref.
20]. The aforementioned studies demonstrated differential viability of
allozyme genotypes where allozyme diversity and divergence were
selected at a microscale or under critical empirically contrasting
conditions and ecologies. Will the noncoding genome also display ecological correlates at
regional and local scales? The answer is emphatically yes for
outbreeding mammals (e.g., ref. 28) and inbreeding wild cereals (e.g.,
refs. 29– 33). Microscale Molecular Population Genetics of Wild Cereals at Four
Israeli Microsites. We used three molecular marker systems that included allozymes,
randomly amplified polymorphic DNAs (RAPD), and microsatellites (SSR)
to detect molecular diversity and divergence in three populations of
wild emmer wheat ( T. dicoccoides); these populations were
from Ammiad, Tabigha, and Yehudiyya microsites in northern Israel, and
these microsites displayed topographic, edaphic, and climatic
ecological contrasts, respectively ( 29– 33). Likewise, we examined
molecular diversity with RAPD and SSR markers in wild barley, H.
spontaneum, in the Tabigha microsite north of the Sea of Galilee,
and in Neve-Yaar, Lower Galilee; the latter microsite represented a
mosaic of microniches of sun, shade, rock, deep soil, and their
combinations. The three marker systems represented protein-coding
(allozyme) regions and noncoding (most of RAPDs) and short repetitive
DNA elements (most of SSRs), hence providing comprehensive coverage of
the wild wheat and barley genomes. At each microsite, we identified
nonrandom divergence of allozyme, RAPD, and SSR diversities.
Significant niche-specific (high frequency in niche type) and
niche-unique (limited to a niche type) alleles and linkage
disequilibria abounded, allowing classification into niches of either
coded or noncoded markers ( 29– 33). At Ammiad, the three marker systems used in wild wheat showed
dramatically different levels of gene diversity ( He) and
genetic distance: SSR > RAPD > allozymes. The gene
differentiation ( Gst) order was allozymes > SSR
> RAPD. Remarkably, the three marker systems revealed similar trends
of diversity and divergence. All three molecular markers displayed
nonrandom allele distributions, habitat-specific and habitat-unique
alleles, and linkage disequilibria ( 29– 33). The subpopulations in the
drier habitats showed higher genetic diversities in the three marker
systems ( 33). The genetic distances among the four subpopulations
tended to increase with the difference of soil moisture after the early
rain of the growing season. These results may suggest that ecological
selection, probably through aridity stress, acts both on structural
protein coding and on presumably partially regulatory noncoding DNA
regions (SSR and RAPD), resulting in microscale adaptive patterns.
Similar microscale molecular (allozymes, RAPDs, SSRs) divergence was
found in two populations of wild barley ( H. spontaneum) at
Tabigha and Neve-Yaar (ref. 11; E. D. Owvor, A. Beharav, T.
Fahima, V. M. Kirzhner, A. B. Korol, and E.N., unpublished
work; and Q. Huang, Y. C. Li, and E.N., unpublished work). Regional Edaphic Selection. The three wild emmer microsites can be classified into two groups
according to their soil types: the terra rossa group (Ammiad + the
terra rossa part of Tabigha) and the basalt group (Yehudiyya + basalt
part of Tabigha). Significant SSR diversity was found between the two
edaphic groups at the regional scale ( 31). In particular, soil-specific
and soil-unique alleles were observed across the Tabigha
microgeographic site and the Ammiad and Yehudiyya regional microsites,
6–8 km away. Permutation tests suggested that the observed
soil-specific and soil-unique alleles were unlikely to occur by chance.
The results indicate that edaphic selection may cause the SSR
divergence in T. dicoccoides between the two edaphic groups
over the entire regional analysis. One of the SSR loci studied (GWM601)
maintained the same allele in the three populations of T.
dicoccoides and its descendant cultivated wheat Triticum
aestivum, suggesting that balancing selection may protect this
locus from any change ( 31). Ecological-Genetic Perspective of SSR Evolution. We reviewed the evidence from a literature survey related to the
importance of functional SSRs, particularly in regulation of gene
activity (transcription and translation), chromatin organization,
genome size, recombination, DNA replication, cell cycle, etc. We also
assembled the ecological-genetic perspectives of SSR evolution based on
other studies besides our wild cereal studies ( 30– 33). We argued that
some SSRs may be of great importance in the process of population
adaptation to environmental stress and that random SSR size expansions
or compressions are selected against. We suggested that balancing and
diversifying ecological selection seem to shape allele-size frequency
distribution and constrain repeat sizes at both the upper and lower
thresholds of SSR (Y. C. Li, A. B. Korol, T. Fahima, A.
Beiles, and E.N., unpublished work; see also ref. 2). The Evolutionary Model of EC: Life's Microcosm. Local, microcosm, and natural laboratories, designated by us as the EC
model, reinforce studies of regional and global macrocosm ecological
theaters across life ( 7, 8). They present sharp ecological contrasts at
a microscale, permitting the pursuit of observations and experiments
across diverse prokaryote and eukaryote taxa sharing a sharp
microecological subdivision. Likewise, they generate theoretical,
testable, and predictable models of biodiversity and genome evolution
and permit the examination of the mode and tempo of adaptation and
speciation. The south-facing slopes (SFS) in canyons north of the
equator receive higher solar radiation than on the nearby north-facing
slopes (NFS; ref. 34). This solar radiation is associated with higher
temperature and drought on the more stressful SFS, causing dramatic
physical and biotic interslope divergence, which may have originated
several million years ago, after mountain uplifts (Fig.
; see also supplemental Fig. 5; refs. 7
and 8). These canyons are extraordinary natural evolutionary
laboratories. If rocks, soils, and topography are similar on the
opposite slopes (50–100 m apart at bottom), microclimate remains the
major interslope divergent factor. Even strongly sedentary organisms
can migrate between slopes. The interslope divergence of biodiversity
(i.e., genes, sequences, genomes, populations, species, ecosystems, and
biota) can be examined within each species distributed on both slopes.
This intraspecific interslope divergence can be compared in many
species across life from prokaryotic bacteria through eukaryotic lower
and higher plants, fungi, and animals ( 7, 8).
These genomic and phenomic multiple taxa interslope comparisons permit
slope-convergent and interslope-divergent generalizations of
organism–environment relationships across life and of the relative
importance of evolutionary forces operating in adaptation and
speciation. In a structural and functional genomic era, all available
complete genomes or those partially sequenced, including stress genes,
are comparable by microarray technology on both slopes along with their
proteomes and phenomes, i.e., at the interrelated molecular and
organismal levels. These long-lived natural evolutionary laboratories
permit in-depth stress studies of genome evolution in adaptation and
speciation in close sympatry and under critical tests of past, present,
and future divergence. Moreover, future critical tests are feasible by
transplant experiments assessing interslope differential fitness and
the dissection of quantitative traits loci by genetic mapping of
families whose parents originated from the opposite slopes. These tests
permit us to focus directly on sets of naturally occurring candidates
and variant fitness genes and traits, which could also be tested
directly by site-specific mutagenesis to assess the importance of
specific amino acids in the function of particular proteins. Finally,
diverse problems like sex and social evolution, among others, as well
as the similar and/or different adaptive strategies between
prokaryotes and eukaryotes can be critically studied at a microsite. ECs I and II: Carmel and Galilee. We opened two long-term research projects in EC I in Lower Nahal Oren,
Mt. Carmel (refs. 7 and 8; Fig. ; supplemental Fig. 4), and EC II in
Lower Nahal Keziv, Upper Western Galilee (ref. 35; supplemental Fig.
5). EC II is 38 km northeast of EC I. In both canyons, we seek local,
regional, and global generalizations across life and organizational
molecular (proteins and DNA) and organismal (morphological,
physiological, and behavioral) levels. Our work at EC I started in 1991
( 7, 8) and at EC II in 1998 ( 35). I summarize our findings below. Species richness. To date, we have identified more than 2,000 species in EC I and more
than 1,000 species in EC II, in an area of 7,000
m 2 in each. The SFS is significantly richer in
species (in both canyons) of “terrestrial” taxa, and the NFS is
richer in “humid” taxa, reflecting locally global patterns (refs.
7 and 8; supplemental Fig. 5; M. Finkel, O. Fragman, and E.N.,
unpublished work). Genetic diversity. Genetic diversity (both of allozymes and DNA) was higher on the
more heterogeneous and stressful SFS in 11 of 14 model organisms (Fig.
; refs. 7 and 8). Remarkably, heritable
mutation rates in the coprophilous fungus S. fimicola were
3-fold higher, and male recombination in D. melanogaster was
4-fold higher on the stressful SFS than on the milder NFS ( 8).
In EC I, we tested, genotypically and phenotypically, two
phylogenetically and biologically very distant organisms, the sessile,
predominantly inbreeding plant wild barley, H. spontaneum,
and the vagile and outbreeding drosophilid fruit fly, Z.
tuberculatus, a very recent colonizer of Israel. The genomes of
these extremely different organisms were tested by AFLP for genetic
diversity at 357 and 345 genetic markers (presumed gene loci),
respectively (E.N., Z. Lu, and T. Pavlicek, unpublished work). We found
in both organisms parallel genetic patterns reflecting the opposite
canyon slopes (Fig. ) with significantly
higher AFLP genetic polymorphism in subpopulations on the ecologically
more stressful, warmer, and drier SFS. Likewise, both organisms
displayed higher viability in response to severe drought stress on the
more arid and climatically fluctuating SFS. Our results suggest the
following. (i) Microclimatic selection is the major
evolutionary interslope fast-acting diverging force on genotypes and
phenotypes, overriding migration and genetic drift. (ii)
Ecological stress can generate global-scale adaptive evolutionary
genome and phenome strategies at both microscales and macroscales,
reinforcing homeostasis and fitness and suggesting continuity
between microevolution and macroevolution.
Extraordinary HIP1 Genome Diversity in a Cyanobacterium N.
linckia. We demonstrated ( 36) in the cyanobacterium N. linckia
from EC I a distinct interslope divergence in AFLP ( 36) and a dramatic
interslope intergenic genetic divergence (Fig. ) of a highly iterated
decameric palindrome (HIP1; refs. 37– 41). The highly stressful
subpopulations 1 and 2, representing the climax of solar radiation,
high temperature, and lowest humidity on SFS, also represent the climax
of size-intergenic HIP1 diversity, (i.e., polymorphism in the size of
intergenic genomic spacing between HIP1 decamers, whose average
distance is about 1.2 kbp ( 39). Hypothetically, HIP1 may be involved in
stability, gene regulation, bacterial chromosome organization, and
genomic rearrangements ( 37– 40), although these assignments await
future demonstration. HIP1 may enhance genome plasticity, increase
genetic diversity, and increase gene rearrangements ( 40) by
intrachromosomal and interchromosomal recombination caused by
replication slippage. We hypothesized, but still seek experimental
evidence, that HIP1 size-intergenic polymorphism is dramatically
selected by spatiotemporal variable climatic stresses at a microscale
as an adaptive strategy to cope with fluctuations of desiccation,
temperature, and solar radiation. The HIP1 size-intergenic polymorphism
may reorganize and increase the genome diversity of N.
linckia and other cyanobacteria, thereby reinforcing their
adaptation to multiple ecological stresses. Haploid sedentary N.
linckia exemplifies the extreme selection of higher genetic
polymorphism caused by microclimatic stress in EC I. Is the extreme
divergence related to the lack of meiotic recombination and absolute
sedentariness in Nostoc? Genome Evolution of Wild Barley by BARE-1 Retrotransposons in EC I. A critical test of the “junk” DNA hypothesis was conducted by
tracking BARE-1 retrotransposon dynamics in wild barley, H.
spontaneum, in EC I ( 42). Genomes abound with “selfish,”
self-replicating retrotransposons “parasitizing” the host DNA.
The BARE-1 retrotransposon constitutes a major, dispersed, active
component of Hordeum genomes, and the BARE-1 copy number is
positively correlated with genome size ( 43). The number of full-length
BARE-1 retrotransposon copies in individuals of H.
spontaneum in EC I ranges from 8.3 ×
10 3 to 22.1 × 10 3 per
haploid genome (i.e., 3-fold variation at a microsite!). What drives
this astonishing local variation? Is it randomly distributed or
ecologically structured? The replicative spread of retrotransposons in
the genome creates new insertion polymorphisms, increasing
retrotransposon numbers and potentially both their share of the genome
and genome size. We examined genome size and BARE-1 insertion patterns and copy
number in wild barley, H. spontaneum, in EC I ( 42). On both
slopes, but especially on the drier SFS, a simultaneous increase in the
BARE-1 copy number and a decrease in the relative number lost through
recombination, as measured by the abundance of solo long terminal
repeats, seem to have driven the BARE-1 share of the genome upward with
the height and dryness of the slope ( 42). The lower recombinational
loss would favor maintenance of more full-length copies, enhancing the
ability of the BARE-1 family to contribute to genome size growth. These
local data are consistent with regional trends for BARE-1 in H.
spontaneum across Israel along a southward transect of increasing
aridity ( 43). This local and regional pattern of BARE-1 may reflect
adaptive selection for increasing genome size through retrotransposon
activity, because larger genomes may cope more effectively with aridity
stress ( 42). Thus, transposable elements may assume new host
mutualistic functions ( 44). Genome Evolution: Adaptive Strategies Against Physical Stresses. Can microscale patterns reflect macroscale adaptive patterns? We tested
interslope genotypic and phenotypic adaptive complexes in diverse
organisms in EC I, from cyanobacteria to mammals. Here, I outline the
adaptive complexes of several model organisms. Morphophysiological, behavioral, and life-history drought-resistant
complex adaptive strategies to the xeric SFS, as compared with those to
the mesic NFS, have been described for wild barley H.
spontaneum ( 45, 46), three woody species ( Olea
europaea, Ceratonia siliqua, and Pistacia
lentiscus; ref. 47), land snails ( 48, 49), D.
melanogaster ( 50), and mammalian rodents ( A. cahirinus
and A. mystacinus; ref. 51). Preliminary findings in spiny
mice, A. cahirinus, showed a desert pattern of basic
metabolic rate lower by 20% on the xeric SFS than on the mesic
NFS. † These xeric adaptations involve
genetic (described earlier) anatomical, ecophysiological, and
behavioral traits to cope with the higher drought on the SFS.
Phenotypic adaptations are intimately coupled with genotypic
adaptations as complex adaptive strategies against single or
combinatorial physical ecological stresses of higher solar radiation,
temperature, and drought on the SFS. Incipient Sympatric Speciation. Interslope adaptive complexes are prerequisites for speciation. Indeed,
we have preliminary evidence for the fruit fly D.
melanogaster ( 52) and the soil fungus S. fimicola ( 53)
of incipient interslope sympatric speciation. Drosophila. Adaptive ecological differentiation of natural populations of D.
melanogaster, D. simulans, and another drosophilid,
Z. tuberculatus, in EC I is well established ( 3). The
fitness complex of D. melanogaster includes oviposition
temperature preferences, tolerance to high temperature, drought stress
and starvation, and different longevity patterns ( 50). This remarkable
differentiation has evolved despite short interslope distances (only
100–400 m), enabling easy dispersal. We hypothesized that interslope
microclimatic differences caused strong diversifying selection for
stress tolerance, accompanied by behavioral differentiation (habitat
choice and reduced migration rate), reinforced by sexual isolation. We
found highly significant mate choice by flies from different slopes of
the canyon, with preference for sexual partners originating from the
same slope ( 52). Preliminary unpublished results (E.N. and T. Pavlicek,
unpublished work) suggest no or low interslope migration as found also
in rodents in EC I ( 11). S. fimicola. Remarkably, we found similar hints of incipient sympatric speciation in
the soil fungus S. fimicola ( 53). Fertility diminished
slightly for interslope strains compared with intraslope crosses. There
was no crossfertility between strains from widely separated areas in
Israel, America, and Canada ( 53). Crossfertility declines with
ecogeographic distance. We are currently testing other taxa between the
slopes for incipient sympatric speciation ( Nostoc,
Lotus, etc.). If substantiated, the EC model may be
embryonic evolutionary cradles of the twin evolutionary processes of
adaptation and speciation across life. Summary of Evidence. The evidence across life, involving numerous species, populations, and
individuals, displays massive genetic polymorphic correlations and
parallelisms to environmental heterogeneity and stress. Generally,
genome and phenome diversity are nonrandom and correlated with stress
and higher environmental heterogeneity or niche width ( 54). Genetic
diversity is partly correlated with, and predictable by, a few
ecological (primarily climatic) variables. These correlations largely
characterize global, regional, and local scales ( 11). Evolutionary Forces and Adaptive Complexes. The aforementioned genomic and phenomic patterns over many unrelated
species, subdivided into ecological contrasts at macroscales and
microscales, strongly implicate natural selection in population and
species differentiation. Various forms of selection, primarily
diversifying, balancing, and cyclical selection regimes are massively
involved, singly or in combination, in genotypic and phenotypic
structure and differentiation of populations and species, at various
life cycle stages of organisms. Natural selection seems to overrule
mutation, migration, and stochasticity in orienting evolution. Natural Selection. Theoretically, spatiotemporal variations of diversifying selection
could maintain genetic polymorphism (55–67). Polymorphism maintenance
may be reinforced by two loci and multilocus structures ( 61– 64) and by
habitat selection ( 67). Heterosis cannot explain multiallele
polymorphism ( 68). Stabilizing Cyclical Selection. Stabilizing selection with a cyclically moving optimum may efficiently
protect polymorphism for linked loci, additively affecting the selected
trait (refs. 61– 64 and references therein). Unequal gene action
and/or dominance effects for one or both loci may lead to local
polymorphism stability with substantial polymorphism attracting domain.
“Supercycles,” with a period comprising hundreds of forced
oscillation periods, could substantiate polymorphism and increase the
range of temporal variation of allele frequencies. A multilocus system
subjected to stabilizing and cycling selection represents a previously
uncharacterized evolutionary mechanism that may increase genetic
diversity over long-term periods ( 63) and contribute to overcoming
massive extinctions. Selection vs. Random Drift. Appreciable polymorphism can be preserved in small, long-isolated
shrinking populations consisting of several dozens or a hundred
individuals, such as in the blind subterranean mole rat,
Spalax ( 66). Current theoretical models predict fast gene
fixation in small panmictic populations without selection, mutation, or
gene inflow. Using simple multilocus models, we demonstrated that
moderate stabilizing selection (with stable or fluctuating optimum) for
traits controlled by additive genes could oppose random fixation in
such isolates for thousands of generations ( 66). We also showed that in
selection-free models, our multichromosome models challenge the
hitchhiking hypothesis ( 69) of polymorphism maintenance for many
neutral loci because of close linkage with a few selected loci. The major conclusion resulting from this modeling is that both
mechanisms (stabilizing selection or cyclical selection) can maintain
polymorphism for many semidominant loci for thousands of generations,
despite a small population size. This negates both Wrightian prediction
on the role of genetic drift in small populations ( 14) and the even
more extreme predictions of the neutral theory ( 13) about random
fixation and low H in small populations. These genetic drift
and neutral scenarios ignore the role of ecological selection in
maintaining genetic polymorphism and predict an unrealistic
straightforward demographic positive correlation between effective
population size and H, regardless of ecological factors. Our
conclusion about the selection in small populations ( 66) is quite
robust in respect to concrete configurations of the selected loci
within and between chromosomes. Strong selection (more than 10% per trait) may be a common phenomenon
in nature, as first emphasized by Ford ( 4). This type of selection
could have important evolutionary consequences in the case of small
peripheral populations ( 66). Our modeling clearly demonstrates that
moderate or strong selection in a small population can oppose random
drift and maintain polymorphism for thousands of generations. These
results are significant for the theories of adaptation and speciation,
particularly for peripatric speciation ( 70). Genetic Interaction Between Species: Biotic Drive of Polymorphism. A simple model of genetic interaction between multiple species governed
by abiotic and biotic selection for multilocus quantitative traits was
recently suggested. The maintenance of polymorphism may result not only
from abiotic, but most importantly, from biotic genetic interaction of
species (host–pathogen, symbionts, competitors) that are governed by
mutual selection for additively controlled quantitative traits ( 71).
Polymorphism seems to be more naturally promoted by unequal gene
effects than by equal gene effects and deviation from purely additive
within-locus schemes of gene action. This new model of species coevolution is based on selection for
quantitative traits, complementing the gene-for-gene concept by a
multilocus trait-for-trait analogue, based on Mendelian formulation
(ref. 71 and references therein). Trait-for-trait interspecies
interaction can promote polymorphism in a species experiencing
selection pressures from other members of the community if at least one
of the following conditions holds: ( i) nonequal effects of
the additive genes controlling the selected trait; ( ii)
dominance deviation from the purely intralocus additivity scheme,
preserving additivity across loci; and ( iii) disturbance of
the log concavity/log convexity of the fitness function of the
considered species. These results may be considered an extension of the
idea of coevolution mediated by selection for qualitative traits, which
was first used in the framework of Lande's quantitative genetic model
( 72). Genetic Diversity Promoted by Ecological Diversity and Stress. The foregoing discussion on both coding and noncoding sequences
suggests several explanations for the maintenance of genetic diversity
subjected to environmental diversity and stress. Spatial and temporal
variation, which predominate in nature, are of prime importance in
maintaining genetic diversity in natural populations. This
ecological–genetic pattern is true, because different genotypes
display varying fitnesses in variable environments and stresses.
Recombination frequencies and mutation rates tend to increase under
stressful conditions ( 73, 74). Rates of evolutionary change are
therefore enhanced in adverse environments. We also showed this
environmental–genetic relationship under controlled laboratory
experiments in the case of mercury pollution ( 75), under regional
aridity stress across the physically stressful environment in
Israel ( 10– 12), and locally in EC because of high solar radiation,
heat, and drought on the SFS ( 7, 8). Genetic polymorphisms at the protein and DNA levels are enhanced under
both environmental stress and genomic stress, as was extensively
documented above. This ecological–genomics pattern could increase
diversity under stressful conditions ( 74). Heterosis may increase
diversity with stress up to high but not extreme levels ( 75).
Environmental heterogeneity and stress cultivate genetic polymorphisms,
particularly in dynamically cycling environments that can generate
complex supercycles, T cycles, and chaotic-like behavior. This mode of
multilocus dynamics far exceeds the potential for maintaining genetic
polymorphism attainable under ordinary selection models, including
heterosis. It may represent a previously uncharacterized evolutionary
mechanism that can assist, in combination with mutation, in maintaining
and increasing genetic polymorphism in single species over long periods
of time, without frequency- and/or density-dependent selection ( 63).
Models of sexual reproduction as an adaptation to resist parasites may
contribute to sex evolution, recombination, and polymorphism ( 76).
Finally, our model of genetic interaction among multiple species
governed by abiotic and biotic selection for multilocus quantitative
traits ( 71), provides additional biotic mechanisms for the promotion of
genetic diversity in nature caused by species' dynamic interactions. The enigma of genetic diversity and genome–phenome organization
and evolution in nature has been fruitfully explored by using modern
molecular techniques. Genotypic and phenotypic diversity has been found
in all species at the protein, DNA, and organismal levels.
Genome–phenome organization in nature is nonrandom, heavily
structured, and correlated with abiotic and environmental diversity and
stress. Deciphering the origin and maintenance of genetic diversity
will be enhanced through investigations focusing on the interface
between ecology and genomics. Critical tests and strong inferences in
nature of abiotic and biotic factors include transplant experiments at
microscales ( 46, 77) and macroscales, to unravel genome organization
and fitness in contrasting and changing environments and to relate
genomics to phenomics. Reassuringly, DNA polymorphisms (RAPDs, AFLPs, SSRs, and SNPs) and the
noncoding genome largely mirror protein (isozyme) polymorphisms are
subjected to natural selection and can be used to highlight genome
structure and evolution. The focus of evolutionary biology is the
organism–environment interaction involving genomes, phenomes, and
biomes, across the tree of life. The noncoding and regulatory genome
should become a central target in understanding evolution. Prospects. What next? Modern molecular techniques, bioinformatics, and
computational techniques make detailed structural–functional genome
analysis possible. The following aspects could be advanced. (i) Probing genomic architecture and dynamics of genes and
intergenic spacers can be facilitated by applying novel DNA polymorphic
molecular markers (RAPD-PCR, AFLP, SSR, or SNP) and sequence
polymorphism, elucidating cell cycling and the evolutionary history of
life as well as bridging genotypes and phenotypes. These techniques can
probe the entire genome, both coding and noncoding regions, especially
in the era of complete comparative and functional genomics. ( ii) Genome sequence variation and marker polymorphism of
stress alleles (i.e., alleles correlated with specific stresses, such
as solar radiation, temperature, drought, salinity, chemical pollution,
and resistances to pathogens and parasites) and SNPs could be probed,
to decipher their biochemical physiology, “chromosome ecology”
( 65), and regulation. ( iii) Testing biomolecular signatures, such as the relative
abundance or “genomic signature” of oligonucleotides, and
analyzing sequence compositional spectra and distribution heterogeneity
of specific signals (methylase targets, telomeric repeats,
microsatellites and minisatellites, palindromes, recombinational hot
spots, mobile elements, and codon usage bias; e.g., ref. 1) provide
powerful tools for comparative ecological-genomic and evolutionary
analysis in diverse taxa across life sharing ecological stresses. These
techniques coupled with transgenics could contribute to evaluating the
function of stress alleles and their control elements under the same
and different stresses. ( iv) From DNA sequencing or structural genomics to
functional genomics: systematic genome mapping, sequencing,
functioning, and experimentation by RNA and DNA microarray chip
technologies offer biology with enormous opportunities and permit
identification and genotyping of mutations and polymorphisms, allowing
better insight into structure-function interaction of genome complexity
under differential stresses ( 78). The completion of sequencing genomes
of many viruses, chloroplasts, mitochondria prokaryotic bacteria,
eukaryotic budding yeast, the nematode
Caenorhabditis elegans, the fruit
fly Drosophila, the higher plant Arabidopsis
thaliana, the important crop rice, Oryza sativa, and
the human genome has permitted the understanding of biodiversity in
molecular terms (e.g., ref. 79 in mammals). Ecological genetics
advanced by Ford ( 4) could now develop into the new science of
ecological genomics, interacting with comparative structural and
functional genomics. What physiological challenges need to be analyzed to reveal the
functions of uncharacterized genes uncovered by sequencing? A promising
approach is to reveal the role of abiotic and biotic ecological factors
in the primary organization and diversity of genomes and their
phenomic–biomic interactions. ( v) Higher resolution
physical maps of chromosomes and genomes of model organisms, including
expressed sequence tags and sequence tagged sites, derived from genetic
mapping of quantitative trait loci by using the new quantitative trait
loci mapping strategy of correlated multitrait complexes ( 80, 81),
and identification of candidate genes, can help unravel the
genetic basis of complex patterns of adaptation and speciation and
substantiate biotechnology. (vi) Identifying, and estimating the kind, degree, and stage
of operation of the following evolutionary forces: natural selection,
migration, mutation, recombination, DNA repair, and mobile elements
operating on the coding and noncoding genome. Molecular diversity
studied under ecological stress allows substantial advances in
understanding genome–proteome–phenome and biome structure, function,
dynamics, and evolution, thereby highlighting the molecular-genetic
basis of adaptation and speciation, i.e., of life's evolution. I thank Sam Karlin, Abraham Korol, and Avigdor Beiles for their
comments on this paper; the University of Haifa for enabling me and my
colleagues to conduct these studies; and all of the many foundations
that financed our efforts to understand genome and phenome diversity
and differentiation in nature. | | EC | evolution canyon | | | AFLP | amplified fragment
length polymorphism | | | SNP | single nucleotide polymorphism | | | SSR | short
sequence repeats | | | RAPD | randomly amplified polymorphic DNA | | | SFS | south-facing slope | | | NFS | north-facing slope |
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