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Results for “balancing selection”

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PubMed2005

Evaluating outlier loci and their effect on the identification of pedigree errors.

Homozygosity outlier loci, which show patterns of variation that are extremely divergent from the rest of the genome, can be evaluated by comparison of the homozygosity under Hardy-Weinberg proportions (the sum of the squares of allele frequencies) with the expected homozygosity under neutrality. Such outlier loci are potentially under selection (balancing selection or directional selection) when genome-wide effects (such as bottleneck and rapid population growth) are excluded. Outlier loci show skewed allele frequencies with respect to neutrality and may therefore affect the identification of pedigree errors. However, choosing neutral markers (excluding outlier loci) for the identification of pedigree errors has been neglected thus far. Our results showed that 4.1%, 5.5%, and 1.5% of the microsatellite markers, Illumina single-nucleotide polymorphisms (SNPs), and Affymetrix SNPs, respectively, on the autosomes appear to be under balancing selection (p or=40%) appear to be under balancing selection. Pedigree structure errors in 15 of 143 pedigrees were detected using microsatellite markers from the autosomes and/or selected SNPs from chromosomes 1 to 18 of the Illumina and/or selected SNPs from chromosomes 1 to 16 of the Affymetrix. Outlier loci did not make a major difference to the identification of pedigree errors. The Collaborative Study on the Genetics of Alcoholism data has pedigree errors and some of them may be due to sample mix up.

Alcoholism↗

PubMed2006

The molecular signature of selection underlying human adaptations.

In the last decade, advances in human population genetics and comparative genomics have resulted in important contributions to our understanding of human genetic diversity and genetic adaptation. For the first time, we are able to reliably detect the signature of natural selection from patterns of DNA polymorphism. Identifying the effects of natural selection in this way provides a crucial piece of evidence needed to support hypotheses of human adaptation. This review provides a detailed description of the theory and analytical approaches used to detect signatures of natural selection in the human genome. We discuss these methods in relation to four classic human traits--skin color, the Duffy blood group, bitter-taste sensation, and lactase persistence. By highlighting these four traits we are able to discuss the ways in which analyses of DNA polymorphism can lead to inferences regarding past histories of selection. Specifically, we can infer the importance of specific regimes of selection (i.e. directional selection, balancing selection, and purifying selection) in the evolution of a trait because these different types of selection leave different patterns of DNA polymorphism. In addition, we demonstrate how these types of data can be used to estimate the time frame in which selection operated on a trait. As the field has advanced, a general issue that has come to the forefront is how specific demographic events in human history, such as population expansions, bottlenecks, and subdivision of populations, have also left a signature across the genome that can interfere with our detection of the footprint of selection at particular genes. Therefore, we discuss this general problem with respect to the four traits reviewed here, and describe the ways in which the signature of selection can be teased from a background signature of demographic history. Finally, we move from a discussion of analyses of selection motivated by a "candidate-gene" approach, in which a priori information led to the analysis of specific gene, to discussion of "genome-scanning" approaches that are directed at discovering new genes that have been under positive selection. Such scans can be designed to detect those genes that have been positively selected in our divergence from chimpanzees, as well as those genes that have been under selection as human populations have migrated, differentiated, and adapted to specific geographic environments. We predict that both approaches will be applied in the future, enabling a greater insight into human species-wide adaptations, as well as the specific adaptations of human populations.

Animals↗

PubMed1992

A comprehensive study of genic variation in natural populations of Drosophila melanogaster. V. Structural-functional constraints on protein molecules and enzymes and the levels and patterns of variation among genes.

Ever since isozyme-allozyme polymorphisms were detected there has been an incessant effort to relate the amount of observed protein variation to various aspects of molecular structure and function. Structural-functional constraints can limit the amount of overall genic variation, and the observed variation can be due to neutral mutation and random genetic drift, mutation-selection balance, or balancing selection. The present analysis of structural-functional constraints on gene-enzyme variation in natural populations of Drosophila melanogaster shows that while both subunit size and substrate group show significant effects on number of alleles and mean heterozygosity, only substrate group affects population structure significantly. Subunit structure (monomer vs. multimer), IUB enzyme class (e.g., transferase, lyase), and tolerance of null alleles showed no significant effect on level or pattern of variation. While partly interdependent, these results suggest that efforts should be made to distinguish between constraints arising from molecular structure and physiological function.

Animals↗

PubMed1995

Gene conversion vs point mutation in generating variability at the antigen recognition site of major histocompatibility complex loci.

In order to assess the roles of gene conversion followed by natural selection and balancing selection for point mutations in polymorphisms at major histocompatibility complex (MHC) loci, DNA sequences of several mammalian taxa were analyzed. Synonymous and nonsynonymous diversities were estimated separately for the antigen recognition site (ARS) and the remaining region of class I and class II genes. In some sequence pairs, the number of nonsynonymous substitutions exceeds that of synonymous substitutions at the ARS. This result indicates that some kind of balancing selection for point mutation is operating. In other sequence pairs (particularly of bovine and of rabbit), the number of synonymous substitutions at the ARS exceeds the same number at the remaining region. This result indicates that gene conversion involving a short region followed by natural selection is important. In general, a combination of gene conversion, point mutation, natural selection and random drift is thought to have contributed to polymorphisms.

Animals↗

PubMed2004

Epidural neostigmine combined with sufentanil provides balanced and selective analgesia in early labor.

BACKGROUND: This study evaluated the efficacy of an epidural single dose of neostigmine combined with sufentanil to provide selective and balanced analgesia at the beginning of labor. METHODS: After informed consent, 125 healthy parturients were randomly allocated to receive, after a test dose, a single injection of either epidural sufentanil 20 micrograms (minimal analgesic dose) or 10 micrograms or a combination of sufentanil 10 micrograms with neostigmine 250, 500, or 750 micrograms in a total volume of 12 ml. Pain scores were recorded at regular intervals to determine onset and duration of analgesia. Maternal and fetal vital parameters as well as side effects were closely monitored. RESULTS: Parturients did not differ concerning demographic data. Epidural neostigmine 500 micrograms with sufentanil 10 micrograms produced effective analgesia (visual analog scale <30 mm within 10 min in 72% parturients and within 15 min in 85% parturients; average duration of 119 min, confidence interval 96-142 min) that was as effective as epidural sufentanil 20 micrograms. Epidural combination with neostigmine 250 micrograms was ineffective, whereas 750 micrograms did not produce higher effect than 500 micrograms. No motor block was recorded. Maternal and fetal vital parameters remained stable during labor. CONCLUSIONS: Epidural combination of neostigmine 500 micrograms (e.g., 6-7 micrograms/kg) with sufentanil 10 micrograms provides similar duration of analgesia as epidural sufentanil 20 micrograms and allows effective and selective analgesia devoid of side effects in the first stage of labor.

Adult↗

PubMed1998

Effects of ZD7114, a selective beta3-adrenoceptor agonist, on neuroendocrine mechanisms controlling energy balance.

Selective beta3-adrenoceptor agonists increase energy expenditure by increasing non-shivering thermogenesis in brown adipose tissue. The aim of this study was to investigate how changes in energy balance affect energy intake and interaction of peripheral metabolic feedback signals with central neuroendocrine mechanisms participating in the control of body energy balance. Expression of preproneuropeptide Y (preproNPY) mRNA in the arcuate nucleus and preprocorticotropin-releasing factor (CRF) mRNA in the paraventricular nucleus were measured by in situ hybridisation technique after 1 day, 1 and 5 weeks of treatment with ZD7114 ((S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2-methoxyet hyl)phenoxyacetamide, 3 mg kg(-1) day(-1) in drinking water) in obese fa/fa Zucker rats. In addition, expression of leptin mRNA in epididymal fat and serum levels of leptin were analysed. Food intake, body weights, binding of GDP to brown adipose tissue mitochondria, plasma insulin and glucose were also measured. Treatment with ZD7114 significantly reduced weight gain and activated brown adipose tissue thermogenesis, but had no effect on food intake. Expressions of preproNPY or preproCRF mRNAs were similarly not changed by treatment with ZD7114. Furthermore, ZD7114 had no effect on plasma insulin or leptin and the expression of leptin mRNA in epididymal fat. However, statistically significant correlations were found between preproNPY and preproCRF mRNA expressions and brown fat thermogenic activity and plasma insulin levels in the ZD7114 treated rats, but not in the control rats. It is concluded that treatment with ZD7114 markedly activated brown fat thermogenesis, but did not affect neuropeptide Y (NPY) and CRF gene expression per se. However, the correlation analyses suggest that ZD7114 may modulate feedback connections of brown adipose tissue thermogenesis and plasma insulin with the hypothalamic neuroendocrine mechanisms integrating body energy balance.

Adipose Tissue, Brown↗

PubMed2001

Geographic heterogeneity in natural selection on an MHC locus in sockeye salmon.

Balancing selection maintains high levels of polymorphism and heterozygosity in genes of the MHC (major histocompatibility complex) of vertebrate organisms, and promotes long evolutionary persistence of individual alleles and strongly differentiated allelic lineages. In this study, genetic variation at the MHC class II DAB-beta1 locus was examined in 31 populations of sockeye salmon (Oncorhynchus nerka) inhabiting the Fraser River drainage of British Columbia, Canada. Twenty-five percent of variation at the locus was partitioned among sockeye populations, as compared with 5% at neutral genetic markers. Geographic heterogeneity of balancing selection was detected among four regions in the Fraser River drainage and among lake systems within regions. High levels of beta1 allelic diversity and heterozygosity, as well as distributions of alleles and allelic lineages that were more even than expected for a neutral locus, indicated the presence of balancing selection in populations throughout much of the interior Fraser drainage. However, proximate populations in the upper Fraser region, and four of six populations from the lower Fraser drainage, exhibited much lower levels of genetic diversity and had beta1 allele frequency distributions in conformance with those expected for a neutral locus, or a locus under directional selection. Pair-wise FST values for beta1 averaged 0.19 and tended to exceed the corresponding values estimated for neutral loci at all levels of population structure, although they were lower among populations experiencing balancing selection than among other populations. The apparent heterogeneity in selection resulted in strong genetic differentiation between geographically proximate populations with and without detectable levels of balancing selection, in stark contrast to observations at neutral loci. The strong partitioning and complex structure of beta1 diversity within and among sockeye populations on a small geographic scale illustrates the value of incorporating adaptive variation into conservation planning for the species.

Alleles↗

PubMed1991

Perturbation-reperturbation test of selection vs. hitchhiking of the two major alleles of Esterase-5 in Drosophila pseudoobscura.

A perturbation-reperturbation tests selective neutrality of 100/100/100/100/100 and 106/100/100/100/100, the two most common alleles at the highly polymorphic X-linked locus Esterase-5 in Drosophila pseudoobscura. A total of 22 replicate populations are set up in cages, 11 start at a high frequency of 76% (U) and 11 at a low frequency of 21% (N) of the 106 allele. Allele frequencies change directionally and decrease in both U and N populations as groups and reach equilibria of 60 and 14%, respectively, after 200-300 days. These changes suggest natural selection. A hypothesis of balancing selection accounts for the pattern and predicts a dynamic equilibrium. A rival neutral hypothesis accounts for the pattern equally well by postulating hitchhiking and breakup of linkage leaving the Est-5 variants to drift at neutral equilibria. A reperturbation of allele frequencies in each population, creating 22 additional reperturbed populations EN and EU, with the original populations as controls, directly addresses the question of balancing selection or hitchhiking and breakup of linkage effects. Allele frequencies do not change directionally among the reperturbed populations as a group. The hypothesis of balancing selection is rejected in favor of the hypothesis of initial hitchhiking and dissipated linkage effects. The power of the experimental design to detect selection is studied by simulation. Within the limits of power set by the design, it is concluded that the 100 and 106 are iso-fitness alleles of Est-5 under the environmental conditions of the laboratory populations. The requirements of a method of perturbation and reperturbation are discussed.

Alleles↗

PubMed2005

Molecular population genetics of herbivore-induced protease inhibitor genes in European aspen (Populus tremula L., Salicaceae).

Plants defend themselves against the attack of natural enemies by using an array of both constitutively expressed and induced defenses. Long-lived woody perennials are overrepresented among plant species that show strong induced defense responses, whereas annual plants and crop species are underrepresented. However, most studies of plant defense genes have been performed on annual or short-lived perennial weeds or crop species. Here I use molecular population genetic methods to survey six wound-inducible protease inhibitors (PIs) in a long-lived woody, perennial plant species, the European aspen (Populus tremula), to evaluate the likelihood of either recurrent selective sweeps or balancing selection maintaining amino acid polymorphisms in these genes. The results show that none of the six PI genes have reduced diversities at synonymous sites, as would be expected in the presence of recurrent selective sweeps. However, several genes show some evidence of nonneutral evolution such as enhanced linkage disequilibrium and a large number of high-frequency-derived mutations. A group of at least four Kunitz trypsin inhibitor genes appear to have experienced elevated levels of nonsynonymous substitutions, indicating allelic turnover on an evolutionary timescale. One gene, TI1, has enhanced levels of intraspecific polymorphism at nonsynonymous sites and also has an unusual haplotype structure characterized by two divergent haplotypes occurring at roughly equal frequencies in the sample. One haplotype has very low levels of intraallelic nucleotide diversity, whereas the other haplotype has levels of diversity comparable to other genes in P. tremula. Patterns of sequence diversity at TI1 do not fit a simple model of either balancing selection or recurrent selective sweeps. This suggests that selection at TI1 is more complex, possibly involving allelic cycling.

Base Sequence↗

PubMed1999

Evolution of HLA class II molecules: Allelic and amino acid site variability across populations.

Analysis of the highly polymorphic beta1 domains of the HLA class II molecules encoded by the DRB1, DQB1, and DPB1 loci reveals contrasting levels of diversity at the allele and amino acid site levels. Statistics of allele frequency distributions, based on Watterson's homozygosity statistic F, reveal distinct evolutionary patterns for these loci in ethnically diverse samples (26 populations for DQB1 and DRB1 and 14 for DPB1). When examined over all populations, the DQB1 locus allelic variation exhibits striking balanced polymorphism (P < 10(-4)), DRB1 shows some evidence of balancing selection (P < 0.06), and while there is overall very little evidence for selection of DPB1 allele frequencies, there is a trend in the direction of balancing selection (P < 0.08). In contrast, at the amino acid level all three loci show strong evidence of balancing selection at some sites. Averaged over polymorphic amino acid sites, DQB1 and DPB1 show similar deviation from neutrality expectations, and both exhibit more balanced polymorphic amino acid sites than DRB1. Across ethnic groups, polymorphisms at many codons show evidence for balancing selection, yet data consistent with directional selection were observed at other codons. Both antigen-binding pocket- and non-pocket-forming amino acid sites show overall deviation from neutrality for all three loci. Only in the case of DRB1 was there a significant difference between pocket- and non-pocket-forming amino acid sites. Our findings indicate that balancing selection at the MHC occurs at the level of polymorphic amino acid residues, and that in many cases this selection is consistent across populations.

Alleles↗

PubMed1998

Migration versus mutation in the evolution of recombination under multilocus selection.

We use modifier theory to compare the evolution of recombination under mutation-selection and migration-selection balance models. Recombination between loosely linked loci subject to weak multilocus selection is controlled by the genotype at a selectively neutral modifier locus. We show that the success of a new modifier depends on the sign and amount of epistasis as well as on the linkage of the modifier locus to the loci under selection. With both migration and mutation, for recombination to increase requires negative (synergistic) epistasis. When epistasis is sufficiently weak, increased recombination is always favoured under mutation-selection balance and never under migration-selection balance. With stronger negative epistasis, there exists a critical recombination value. In this case, a recombination-increasing allele invades the population under mutation-selection balance if its recombination rate with the major loci is less than the critical recombination value, whereas with weak migration it must be above this value. These results are the same for haploid and diploid populations.

Biological Evolution↗

PubMed2005

Duloxetine: a balanced and selective norepinephrine- and serotonin-reuptake inhibitor.

PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, drug interactions, dosage and administration, cost, and place in therapy of duloxetine for major depression, pain from diabetic peripheral neuropathy, and stress urinary incontinence are reviewed. SUMMARY: Duloxetine is a balanced selective serotonin and norepinephrine-reuptake inhibitor available in the United States for the treatment of major depressive disorder (MDD) and diabetic peripheral neuropathic pain (DPNP). Duloxetine has also been used for the treatment of stress urinary incontinence (SUI). Absorption of duloxetine begins two hours after oral administration, reaching a maximum plasma concentration in six hours. Half-life and volume of distribution are 12 hours and 1640 L, respectively. The recommended dosage of duloxetine is 40-80 mg daily, depending on the indication, preferably split into two doses per day. For the treatment of major depression, duloxetine has achieved remission rates similar to that of existing selective serotonin-reuptake inhibitors (SSRIs). For SUI and pain associated with diabetic peripheral neuropathy, duloxetine has not demonstrated equivalence or superiority to existing therapies. The adverse effects of duloxetine are similar to those of traditional SSRIs. Nausea is common and has been cited as the primary reason for discontinuation of duloxetine in trials. Increases in blood pressure have been mild, but caution should be used in patients with hypertension. Patients with a creatinine clearance of <30 mL/min and patients with hepatic impairment should avoid duloxetine. Duloxetine should not be recommended as first-line therapy for SUI or DPNP. For MDD, duloxetine may be a useful alternative for patients who do not benefit from or are unable to tolerate other antidepressant therapy. CONCLUSION: Duloxetine has been approved for the treatment of MDD and pain associated with diabetic peripheral neuropathy in adults.

Adrenergic Uptake Inhibitors↗

PubMedDate not supplied

Locus-specific genetic diversity between human populations: an analysis of the literature.

The debate over classification of the human species according to racial or continental lines has involved reports on genetic differences in allele frequencies of a number of loci with important biomedical functions. Such differences are in contrast with the fact that, for human beings, intrapopulation genetic diversity is larger than that seen between populations. In an attempt to address the hypothesis that certain genes show high interpopulation diversity due to selective pressure, the literature was surveyed to quantify such diversity using Wrights Fst statistic. The gene-specific Fst values were then compared to pairwise population values of Fst taken over a large number of genes, which presumably reflect mostly neutral mechanisms of genetic diversity such as drift. The results showed that the majority of pairwise population values of Fst for over 30 genes of biomedical significance were either below or within the expected limits of Fst based on published values. These results do not support the idea that positive or diversifying natural selection plays an important role in increasing genetic diversity, even in genes that might be expected to be subject to selection pressure. Balancing selection, whereby the degree of genetic diversity is actually lower than that expected, appears to occur more frequently for these genes. The fact that allele frequency differences between populations might be "statistically significant" does not therefore necessarily imply a degree of genetic diversity greater than would be expected due to nonselective mechanisms.

Chromosome Mapping↗

PubMed2005

Natural selection on protein-coding genes in the human genome.

Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection. The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly, with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection, and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations. Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees.

Amino Acid Substitution↗

PubMed2005

Prospects for identifying functional variation across the genome.

The genetic factors contributing to complex trait variation may reside in regulatory, rather than protein-coding portions of the genome. Within noncoding regions, SNPs in regulatory elements are more likely to contribute to phenotypic variation than those in nonregulatory regions. Thus, it is important to be able to identify and annotate noncoding regulatory elements. DNA conservation among diverged species successfully identifies noncoding regulatory regions. However, because rapidly evolving regulatory regions will not generally be conserved across species, these will not detected by using purely conservation-based methods. Here we describe additional approaches that can be used to identify putative regulatory elements via signatures of nonneutral evolution. An examination of the pattern of polymorphism both within and between populations of Drosophila melanogaster, as well as divergence with its sibling species Drosophila simulans, across 24.2 kb of noncoding DNA identifies several nonneutrally evolving regions not identified by conservation. Because different methods tag different regions, it appears that the methods are complementary. Patterns of variation at different elements are consistent with the action of selective sweeps, balancing selection, or population differentiation. Together with regions conserved between D. melanogaster and Drosophila pseudoobscura, we tag 5.3 kb of noncoding DNA as potentially regulatory. Ninety-seven of the 408 common noncoding SNPs surveyed are within putatively regulatory regions. If these methods collectively identify the majority of functional noncoding polymorphisms, genotyping only these SNPs in an association mapping framework would reduce genotyping effort for noncoding regions 4-fold.

Animals↗

PubMed2000

Selection-mutation balance in polysomic tetraploids: impact of double reduction and gametophytic selection on the frequency and subchromosomal localization of deleterious mutations.

We modeled the behavior of recessive mutations with deleterious effects to either the sporophyte or the gametophyte, or both, in polysomic tetraploid populations by allowing for varying levels of double reduction, mutation, and self-fertilization. Double reduction causes a decrease of the equilibrium frequencies of deleterious alleles, and it has much more influence on genes subjected to gametophytic selection than on genes solely under sporophytic selection. With gametophytic selection, low frequencies of double reduction are enough to reduce equilibrium frequencies severalfold. Double reduction occurs when sister alleles migrate to the same gamete during meiosis. It depends on the frequency at which a locus recombines with its centromere, and on the frequency of multivalent formation. Therefore, a greater accumulation of deleterious mutations should occur on polysomic chromosomes with a prevalence of bivalent pairing and in chromosomal regions between centromeres and proximal chiasmata. Proximal loci should have a greater impact in reducing the fitness of a polyploid population being inbred. This prediction can explain observations that homozygosities at different subchromosomal regions have distinct effects on inbreeding depression in polyploids. Furthermore, even mildly deleterious alleles can lead to large amounts of inbreeding depression because of their high equilibrium frequencies. Molecular studies correlating level of heterozygosity and degree of heterosis should take into account this nonuniform distribution of deleterious alleles in polyploid genomes. Preservation or enhancement of heterozygosity would be more critical at proximal regions than at other chromosome regions in polysomic polyploid species.

Alleles↗

PubMed1994

On the distribution of the mean and variance of a quantitative trait under mutation-selection-drift balance.

The distributions of the mean phenotype and of the genetic variance of a polygenic trait under a balance between mutation, stabilizing selection and genetic drift are investigated. This is done by stochastic simulations in which each individual and each gene are represented. The results are compared with theoretical predictions. Some aspects of the existing theories for the evolution of quantitative traits are discussed. The maintenance of genetic variance and the average dynamics of phenotypic evolution in finite populations (with Ne < 1000) are generally simpler than those suggested by some recent deterministic theories for infinite populations.

Chromosome Mapping↗

PubMed2004

[Nucleotide polymorphism in the drought induced transcription factor CBF4 region of Arabidopsis thaliana and its molecular evolution analyses].

Intraspecific nucleotide polymorphism in the drought induced transcription factor CBF4 region of Arabidopsis thaliana was analyzed with 17 core accessions growing in different ecoclimate. High density of single nucleotide polymorphism (SNP) and insertion/deletion (Indel) were found, on average 1 SNP per 35.8 bp and 1 Indel per 143 bp. Nucleotide polymorphism in non-coding region was three times higher than that in coding region. In coding region of CBF4, SNP frequency is one SNP per 96.4 bp, one nonsynonymous mutation was detected from 25 av, 203 av and 244 av accessions, which is the 205th site amino acid variation: gly <--> val caused by the 1034th site (corresponding to 19,696 site nucleotide of GenBank No. AB015478 as 1) nucleotide variation: G <--> T. Statistical result of nucleotide diversity showed that linkage disequilibrium (LD) existed in large-scale region of CBF4 and recombination event was also detected in 5' non-coding region. Identical to the results of other genes of Arabidopsis, different regions of the gene were seemingly under different selective pressures. Balancing selection resulted in high nucleotide diversity in 3' non-coding region, and the neutral mutation hypothesis can explain the DNA polymorphism in coding region, whereas, nature positive selection in the population affected nucleotide variation in 5' non-coding region of gene.

Arabidopsis↗