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1.
Nucleotide polymorphism at the pantophysin (Pan I) locus in walleye pollock, Theragra chalcogramma, was examined using DNA sequence data. Two distinct allelic lineages were detected in pollock, resulting from three amino acid replacement mutations in the first intravesicular domain of the protein. The common Pan I allelic group, comprising 94% of the samples, was less polymorphic (pi = 0.005) than the uncommon group (pi = 0.008), and nucleotide diversity in both was higher than for two allelic lineages in the related Atlantic cod, Gadus morhua. Phylogenetic analyses of Pan I sequences from these two species did not clearly resolve orthology among allelic groups, in part because of recombination that has occurred between the two pollock lineages. Conventional tests of neutrality comparing polymorphisms within and between homologous regions of the Pan I locus in walleye pollock and Atlantic cod did not detect the effects of selection. This result is likely attributed to low levels of synonymous divergence among allelic lineages and a lack of mutation-drift equilibrium inferred from nucleotide mismatch frequency distributions. However, the ratio of nonsynonymous to synonymous substitutions per site (dN/dS) exceeded unity in two intravesicular domains of the protein and the influence of positive selection at multiple codon sites was strongly inferred through the use of maximum-likelihood analyses. In addition, the frequency spectrum of linked neutral variation showed indirect effects of adaptive hitchhiking in pollock resulting from a selective sweep of the common allelic lineage. Recombination between the two allelic classes may have prevented complete loss of the older, more polymorphic lineage. The results suggest that recurrent sweeps driven by positive selection is the principle mode of evolution at the Pan I locus in gadid fishes. 相似文献
2.
More than 6000 cod Gadus morhua , sampled in coastal and offshore waters stretching from the Barents Sea down to the North Sea, were analysed for frequencies of alleles at the scnDNA pantophysin locus ( Pan I)[formerly called synaptophysin ( Syp I)]. The significant allele frequency difference between the two major stocks of cod in Norway, north‐east Arctic cod (NEAC) and Norwegian coastal cod (NCC), was upheld in all years of the investigation (1993 to 2001), and applied both to larval cod and post‐juveniles of various ages. On a north‐south axis, the appearance of a latitudinal cline of post‐juvenile (≥1 year) allele frequencies was exposed. The intermediate allele frequencies in coastal areas of northern Norway, seem to a large extent to be caused by intermingling of the two stocks, although the existence of populations of coastal cod with alternative Pan I frequencies could not be ruled out. The role of selection is yet unresolved. Depth of the sampling location seemed to have an effect on the allele frequencies and their temporal stability, while there was no indication of seasonal variation in the frequencies. Breeding structure was the most likely cause for upholding the extreme divergence in Pan I frequencies between NEAC and NCC. 相似文献
3.
We used the polymerase chain reaction (PCR) and direct DNA sequencing to study genetic variation within and among populations of Atlantic cod, Gadus morhua , in the western North Atlantic. In a 307 bp region of the mitochondrial cytochrome b gene, 24 variable nucleotide positions define 24 genotypes, which differ by from one to six nucleotide substitutions. Greenland cod ( G. ogac ) differs from the most similar G. morhua genotype by an additional 12 nucleotide substitutions. Silent transitions dominate both intra- and interspecific comparisons, however four nucleotide substitutions within morhua result in amino acid replacements. Direct sequencing of DNA reveals substantially more of the genetic variation that exists within and between species than do previous indirect methods based on restriction fragment length polymorphisms, and thus has far greater potential to quantify such differences as may exist among fish stocks. Preliminary experiments also indicate that automation of DNA sequencing provides an efficient, rapid, and accurate means for detection of genetic variation in natural populations offish. 相似文献
4.
Variation at seven microsatellite loci was compared with variation observed at Pan I, a single copy nuclear DNA gene coding for pantophysin, in 14 samples of Atlantic cod ( Gadus morhua ) stretching from Spitsbergen to the North Sea. Population structuring indicated by the two types of markers was concordant and in agreement with the traditional grouping of cod in the study area into three main populations: north-east Arctic cod (NEAC), Norwegian coastal cod (NCC) and North Sea cod (NSC). Microsatellites, however, revealed genetic heterogeneity not only within NCC, as did Pan I, but also within NEAC and NSC, which appeared to be homogenous when analysed for Pan I. Moreover, microsatellites displayed lower levels of differentiation than Pan I between NEAC and two other groups. Differences in the magnitude of differentiation for the two types of markers may be attributable to higher levels of polymorphism and alleged selective neutrality of microsatellites. Isolation by distance was clearly apparent for microsatellites but was less evident for Pan I, indicating that environmentally induced selection appears to shape the patterns of genetic differentiation for this marker. Even though the population structure of north-east Atlantic cod, as revealed by microsatellites and Pan I, appears to be maintained largely by restricted gene flow, selection acting on a recent historical time scale probably contributes to the observed geographic pattern of Pan I frequencies. 相似文献
5.
Moreno-Estrada A Casals F Ramírez-Soriano A Oliva B Calafell F Bertranpetit J Bosch E 《Molecular biology and evolution》2008,25(1):144-154
The human olfactory receptor (OR) repertoire is reduced in comparison to other mammals and to other nonhuman primates. Nonetheless, this olfactory decline opens an opportunity for evolutionary innovation and improvement. In the present study, we focus on an OR gene, OR5I1, which had previously been shown to present an excess of amino acid replacement substitutions between humans and chimpanzees. We analyze the genetic variation in OR5I1 in a large worldwide human panel and find an excess of derived alleles segregating at relatively high frequencies in all populations. Additional evidence for selection includes departures from neutrality in allele frequency spectra tests but no unusually extended haplotype structure. Moreover, molecular structural inference suggests that one of the nonsynonymous polymorphisms defining the presumably adaptive protein form of OR5I1 may alter the functional binding properties of the OR. These results are compatible with positive selection having modeled the pattern of variation found in the OR5I1 gene and with a relatively ancient, mild selective sweep predating the "Out of Africa" expansion of modern humans. 相似文献
6.
Positive and negative selection on the human genome. 总被引:42,自引:0,他引:42
The distinction between deleterious, neutral, and adaptive mutations is a fundamental problem in the study of molecular evolution. Two significant quantities are the fraction of DNA variation in natural populations that is deleterious and destined to be eliminated and the fraction of fixed differences between species driven by positive Darwinian selection. We estimate these quantities using the large number of human genes for which there are polymorphism and divergence data. The fraction of amino acid mutations that is neutral is estimated to be 0.20 from the ratio of common amino acid (A) to synonymous (S) single nucleotide polymorphisms (SNPs) at frequencies of > or =15%. Among the 80% of amino acid mutations that are deleterious at least 20% of them are only slightly deleterious and often attain frequencies of 1-10%. We estimate that these slightly deleterious mutations comprise at least 3% of amino acid SNPs in the average individual or at least 300 per diploid genome. This estimate is not sensitive to human population history. The A/S ratio of fixed differences is greater than that of common SNPs and suggests that a large fraction of protein divergence is adaptive and driven by positive Darwinian selection. 相似文献
7.
为研究鸡MHC B-LBⅡ基因的遗传多态性,首先在8个中国地方鸡种(藏鸡、仙居鸡、北京油鸡、固始鸡、斗鸡、丝羽乌骨鸡、白耳鸡和狼山鸡)B-LBⅡ基因第二外显子扩增了一长度为 175 bp 的 DNA 片段并进行 SSCP 基因型分析;在8 个地方鸡种共 467 个个体中检测到 37 个 PCR-SSCP 基因型;从被检样品中筛选出不同基因型的个体,并在其 B-LBⅡ基因组中扩增了一个包括其第二外显子和第二内含子在内长度为374 bp的片段,通过克隆和测序获得了该片段的核苷酸序列。经序列分析,在前述地方鸡种被筛选出的 30 个无血缘关系的个体中发现了 31 个 B-LBⅡ新等位基因,并参照哺乳动物 MHC II 类 B 等位基因命名规则进行了命名。对这 31 个 B-LBⅡ新等位基因长度为 374 bp 的 DNA 片段进行比对表明,在其第二外显子序列上共有 68 个多态性变异位点,其中简约性信息位点 51 个,单变异位点 17 个,具有丰富的遗传多态性。在这些多态性变异位点中,出现在遗传密码子第一和第二位上的碱基替换率分别为 36.76% 和 35.29%。等位基因序列间的相似性估测为 90.6%-99.5%;B-LBⅡ基因第二外显子的错义替换率和同义替换率分别为 14.64±2.67%和 2.92±0.94%。结果表明,B-LBⅡ基因的丰富遗传多态性主要是由基因重组和平衡选择效应所引起的。对 B-LBⅡ等位基因第二外显子所编码的 B-LBⅡ分子β1 结构域氨基酸序列比对发现,31 个 B-LBⅡ新等位基因属于 26 个等位基因主型;在β1结构域氨基酸序列的 33个变异位点上,存在 6 个同义替换和 27 个错义替换。分析认为,那些发生在多肽结合位点上的氨基酸错义替换与鸡 MHC B-LBⅡ分子的免疫特异性有关。该结果可为鸡的抗病育种研究提供分子生物学依据。 相似文献
8.
根据鸡主要组织相容性复合体B-LBⅡ基因序列设计特异性引物,在藏鸡基因组中扩增了一个包括其第二外显子和第二内含子在内长度为374 bp的片段,并通过克隆和PCR直接测序获得了该片段的核苷酸序列。发现了15个B-LBⅡ新等位基因。对18个B-LBⅡ等位基因核苷酸序列和其所编码的MHCB-LBⅡ分子β1结构域的氨基酸序列分析显示,第二外显子核苷酸序列遗传多态性异常丰富,存在着62个多态变异位点(共包括80个突变),其中41个为简约性多态位点;衡量该序列遗传多样性的π值为0.0718;反映其群体内遗传变异度的平均遗传距离为0.056±0.008,低于在5个外来品种所估算的平均遗传距离。该编码区核苷酸相对异义替换率(15.61±2.69%)显著高于其同义替换率(3.25±0.94%),进一步分析表明,基因重组和平衡选择机制可能是引起B-LBⅡ基因序列变异的主要因素。在β1结构域氨基酸序列中,存在11个同义替换和27个异义替换;在24个肽结合位点中有12个变异位点;与其他6个中国地方鸡品种和一个外来品种比较发现,有11个异义氨基酸替换仅出现在藏鸡群体中,并被认为与藏鸡的免疫特异性有关,可为鸡的抗病力研究提供分子依据。 相似文献
9.
Higgins LE White S Nuñez-Farfán J Vargas J 《International journal of biological macromolecules》2007,40(3):201-216
Spider silk proteins and their genes are very attractive to researchers in a wide range of disciplines because they permit linking many levels of organization. However, hypotheses of silk gene evolution have been built primarily upon single sequences of each gene each species, and little is known about allelic variation within a species. Silk genes are known for their repeat structure with high levels of homogenization of nucleotide and amino acid sequence among repeated units. One common explanation for this homogeneity is gene convergence. To test this model, we sequenced multiple alleles of one intron-exon segment from the Flag gene from four populations of the spider Nephila clavipes and compared the new sequences to a published sequence. Our analysis revealed very high levels of heterozygosity in this gene, with no pattern of population differentiation. There was no evidence of gene convergence within any of these alleles, with high levels of nucleotide and amino acid substitution among the repeating motifs. Our data suggest that minimally, there is relaxed selection on mutations in this gene and that there may actually be positive selection for heterozygosity. 相似文献
10.
Maximum-likelihood models of codon substitution were used to test for positive Darwinian selection at the vesicle protein pantophysin in two allelic lineages segregating in the Atlantic cod Gadus morhua and in 18 related species of marine gadid fishes. Positive selection was detected in the two intravesicular loops of the integral membrane protein but not in four membrane-spanning regions or the 3' cytoplasmic tail. The proportion of positively selected sites (24.9%) and the mean nonsynonymous/synonymous rate ratio (omega = d(N)/d(S) = 5.35) were both greater in the first intravesicular (IV1) domain compared with the second intravesicular (IV2) domain (11.0% positively selected sites with mean omega = 3.76). Likelihood ratio tests comparing models that assume identical omega ratios along all branches of the phylogeny to those that allow omega ratios to vary among lineages were not significant for either the IV1 or IV2 domains, indicating that the selective pressures favoring amino acid replacements have operated consistently in both regions during the diversification of the group. Positive selection was observed in the IV1 domain in both G. morhua allelic lineages, and, although three of the four codons that differ between alleles were targets of positive selection in the broader group, no similar polymorphisms were detected in other taxa. The two G. morhua Pan I alleles appeared to have evolved before the speciation event separating it from its sister taxon, Theragra chalcogramma, and on the basis of a standard mtDNA clock are estimated to be at least 2 Myr old. Although the function of pantophysin remains unknown, the strong signal of positive selection at specific sites in the IV1 and IV2 domains may help clarify its role in cellular trafficking pathways. 相似文献
11.
Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene. 总被引:3,自引:0,他引:3
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S. L. Primo-Parmo C. F. Bartels B. Wiersema A. F. van der Spek J. W. Innis B. N. La Du 《American journal of human genetics》1996,58(1):52-64
The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity <10% of the average levels of the usual phenotype. Heterogeneity in this phenotype has been well established at the phenotypic level, but only a few silent BCHE alleles have been characterized at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene (BCHE) have been identified in 17 apparently unrelated patients who were selected by their increased sensitivity to the muscle relaxant succinylcholine. All of these alleles are characterized by single nucleotide substitutions or deletions leading to distinct changes in the structure of the BChE enzyme molecule. Nine of the nucleotide substitutions result in the replacement of single amino acid residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce normal amounts of immunoreactive but enzymatically inactive BChE protein in the plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F, BCHE*170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of BChE protein, and their role in determining the silent phenotype was confirmed by expression in cell culture. The other four silent alleles, BCHE*271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChES truncated at their C-terminus because of premature stop codons caused by nucleotide substitutions, a frame shift, or altered splicing. The large number of different silent BCHE alleles found within a relatively small number of patients shows that the heterogeneity of the silent BChE phenotype is high. The characterization of silent BChE variants will be useful in the study of the structure/function relationship for this and other closely related enzymes. 相似文献
12.
Genetic variation at the melanocortin-1 receptor (MC1R) gene is correlated with melanin color variation in a few reported vertebrates. In Gyrfalcon (Falco rusticolus), plumage color variation exists throughout their arctic and subarctic circumpolar distribution, from white to gray and almost black. Multiple color variants do exist within the majority of populations; however, a few areas (e.g., northern Greenland and Iceland) possess a single color variant. Here, we show that the white/melanic color pattern observed in Gyrfalcons is explained by allelic variation at MC1R. Six nucleotide substitutions in MC1R resulted in 9 alleles that differed in geographic frequency with at least 2 MC1R alleles observed in almost all sampled populations in Greenland, Iceland, Canada, and Alaska. In north Greenland, where white Gyrfalcons predominate, a single MC1R allele was observed at high frequency (>98%), whereas in Iceland, where only gray Gyrfalcons are known to breed, 7 alleles were observed. Of the 6 nucleotide substitutions, 3 resulted in amino acid substitutions, one of which (Val(128)Ile) was perfectly associated with the white/melanic polymorphism. Furthermore, the degree of melanism was correlated with number of MC1R variant alleles, with silver Gyrfalcons all heterozygous and the majority of dark gray individuals homozygous (Ile(128)). These results provide strong support that MC1R is associated with plumage color in this species. 相似文献
13.
A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects 总被引:2,自引:1,他引:2
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A Mimori Y Hidaka V C Wu S A Tarlé N Kamatani W N Kelley T D Pallela 《American journal of human genetics》1991,48(1):103-107
Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disorder which causes 2,8-dihydroxy-adenine urolithiasis. The estimated incidence of heterozygosity in Caucasian and Japanese populations is 1%. Mutant alleles responsible for the disease have been classified as APRT*Q0 (type I) and APRT* (type II). In our previous study, we demonstrated in APRT*J a single common base change which accounts for 70% of the Japanese mutants. The present report describes the analysis of an APRT*Q0 mutation in Japanese subjects. Two nucleotide substitutions common to all seven affected alleles from four unrelated subjects (three homozygotes and a heterozygote) were identified: G----A at nucleotide position 1453 and C----T at 1456. The G----A altered the amino acid Trp98 to a stop codon. The C----T did not alter Ala99. These point mutations were demonstrated by sequence analysis of polymerase chain reaction (PCR)-amplified genomic DNA and cDNA. The G----A change at 1453 results in the elimination of a PflMI site in the APRT gene. PflMI digests, which were used to confirm the G----A transition, can be useful in screening for this specific mutation. 相似文献
14.
Kirby RR 《Molecular biology and evolution》2000,17(12):1816-1825
Clines in intraspecific genetic variation are frequently associated with an environmental transition. Here, divergence among nucleotide sequences of two nuclear loci, cytosolic and mitochondrial malate dehydrogenase (cMDH and mMDH, respectively), is described, in a multitrait cline over a distance of ca. 3 km where shell phenotype, allozyme, mitochondrial DNA haplotype, and centric fusion (Robertsonian translocations) frequencies covary with temperature and humidity and change abruptly in a continuous population of the dog-whelk (Nucella lapillus), a common intertidal snail of the north temperate Atlantic. Protein electrophoresis has already shown two alleles of mMDH varying from fixation of one allele to near fixation of the other, whereas cMDH appears to be monomorphic. The results of this study show a striking disparity in nucleotide sequence divergence among alleles at the two loci, with extreme molecular differentiation in one of them. Four alleles of cMDH were found to have nucleotide and amino acid sequence divergences of 0.4% and 0.3%, respectively. In contrast, the two mMDH cDNA alleles differed by 23% and 20% at the nucleotide and amino acid levels, respectively. Analysis of a 91-bp partial nucleotide sequence of mMDH from Nucella freycineti, the closest relative of N. lapillus, revealed two similar alleles and indicated that the divergence in mMDH in N. lapillus represents an ancient transpecific polymorphism in these Nucella. Together with earlier studies on variation in N. lapillus, it is argued that the polymorphism in mMDH and the clines in N. lapillus represent the presence of two persistent coadapted gene complexes, multitrait coevolving genetic solutions to environmental variation, which may presently enable this snail to exploit a diverse environment successfully. 相似文献
15.
Abstract. 1. Allozyme alleles in natural populations have been proposed as either neutral markers of genetic diversity or the product of natural selection on enzyme function, as amino acid substitutions that change electrophoretic mobility may also alter enzyme performance. To address these possibilities, researchers have used both correlative analyses and empirical studies.
2. Here, geographically structured variation of the enzyme isocitrate dehydrogenase ( Idh- 1) in the striped ground cricket Allonemobius socius Scudder (Orthoptera: Gryllidae) is examined. The distributions of Idh- 1 alleles appear to be related to environmental gradients, as allele frequencies showed significant relationships with mean annual temperature and precipitation. Specifically, the slowest mobility allele was more frequent at colder temperatures, while the converse occurred for the fastest mobility allele.
3. An exploratory experiment was performed to examine fitness effects of possessing different Idh- 1 alleles at two temperatures to test the hypothesis that the geographic structure of this locus may reflect environmental adaptation. Results showed that a significant interaction between temperature and Idh- 1 genotype affected the number of eggs laid, with success of homozygous individuals matching environmental expectations.
4. The above results show that (1) variation in the frequency of Idh- 1 alleles is significantly related to environmental gradients in the eastern U.S.A. and (2) alternative alleles of Idh- 1 appear to influence the egg-laying ability of individuals differently depending on environmental temperature. Together, these results suggest that natural selection is a plausible mechanism underlying the distribution of Idh- 1 alleles in this species, although more detailed studies are needed. 相似文献
2. Here, geographically structured variation of the enzyme isocitrate dehydrogenase ( Idh- 1) in the striped ground cricket Allonemobius socius Scudder (Orthoptera: Gryllidae) is examined. The distributions of Idh- 1 alleles appear to be related to environmental gradients, as allele frequencies showed significant relationships with mean annual temperature and precipitation. Specifically, the slowest mobility allele was more frequent at colder temperatures, while the converse occurred for the fastest mobility allele.
3. An exploratory experiment was performed to examine fitness effects of possessing different Idh- 1 alleles at two temperatures to test the hypothesis that the geographic structure of this locus may reflect environmental adaptation. Results showed that a significant interaction between temperature and Idh- 1 genotype affected the number of eggs laid, with success of homozygous individuals matching environmental expectations.
4. The above results show that (1) variation in the frequency of Idh- 1 alleles is significantly related to environmental gradients in the eastern U.S.A. and (2) alternative alleles of Idh- 1 appear to influence the egg-laying ability of individuals differently depending on environmental temperature. Together, these results suggest that natural selection is a plausible mechanism underlying the distribution of Idh- 1 alleles in this species, although more detailed studies are needed. 相似文献
16.
Two species of crickets, Gryllus veletis and G. pennsylvanicus, share six electrophoretic mobility classes for the enzyme phosphoglucose isomerase (PGI), despite evidence from other genetic markers that the two species are not closely related within eastern North American field crickets. Moreover, the frequencies of the two most common PGI electrophoretic classes (PGI-100 and PGI-65) covary in sympatric populations of these species in the eastern United States, suggesting that PGI may be subject to trans-specific balancing selection. To determine the molecular basis of the electrophoretic variation, we characterized the DNA sequence of the Pgi gene from 29 crickets (15 G. veletis and 14 G. pennsylvanicus). Amino acid substitutions that distinguish the electrophoretic classes are not the same in the two species, and there is no evidence that specific replacement substitutions represent trans-specific polymorphism. In particular, the amino acids that diagnose the PGI-65 allele relative to the PGI-100 allele differ both between G. veletis and G. pennsylvanicus and within G. pennsylvanicus. The heterogeneity among electrophoretic classes that covary in sympatric populations coupled with analysis of patterns of nucleotide variation suggest that Pgi is not evolving neutrally. Instead, the data are consistent with balancing selection operating on an emergent property of the PGI protein. 相似文献
17.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. Deficiency alleles for this X-linked disorder are geographically correlated with historical patterns of malaria, and the most common deficiency allele in Africa (G6PD A-) has been shown to confer some resistance to malaria in both hemizygous males and heterozygous females. We studied DNA sequence variation in 5.1 kb of G6pd from 47 individuals representing a worldwide sample to examine the impact of selection on patterns of human nucleotide diversity and to infer the evolutionary history of the G6PD A- allele. We also sequenced 3.7 kb of a neighboring locus, L1cam, from the same set of individuals to study the effect of selection on patterns of linkage disequilibrium. Despite strong clinical evidence for malarial selection maintaining G6PD deficiency alleles in human populations, the overall level of nucleotide heterozygosity at G6pd is typical of other genes on the X chromosome. However, the signature of selection is evident in the absence of genetic variation among A- alleles from different parts of Africa and in the unusually high levels of linkage disequilibrium over a considerable distance of the X chromosome. In spite of a long-term association between Plasmodium falciparum and the ancestors of modern humans, patterns of nucleotide variability and linkage disequilibrium suggest that the A- allele arose in Africa only within the last 10,000 years and spread due to selection. 相似文献
18.
Evidence for balancing selection from nucleotide sequence analyses of human G6PD 总被引:7,自引:0,他引:7
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Verrelli BC McDonald JH Argyropoulos G Destro-Bisol G Froment A Drousiotou A Lefranc G Helal AN Loiselet J Tishkoff SA 《American journal of human genetics》2002,71(5):1112-1128
Glucose-6-phosphate dehydrogenase (G6PD) mutations that result in reduced enzyme activity have been implicated in malarial resistance and constitute one of the best examples of selection in the human genome. In the present study, we characterize the nucleotide diversity across a 5.2-kb region of G6PD in a sample of 160 Africans and 56 non-Africans, to determine how selection has shaped patterns of DNA variation at this gene. Our global sample of enzymatically normal B alleles and A, A-, and Med alleles with reduced enzyme activities reveals many previously uncharacterized silent-site polymorphisms. In comparison with the absence of amino acid divergence between human and chimpanzee G6PD sequences, we find that the number of G6PD amino acid polymorphisms in human populations is significantly high. Unlike many other G6PD-activity alleles with reduced activity, we find that the age of the A variant, which is common in Africa, may not be consistent with the recent emergence of severe malaria and therefore may have originally had a historically different adaptive function. Overall, our observations strongly support previous genotype-phenotype association studies that proposed that balancing selection maintains G6PD deficiencies within human populations. The present study demonstrates that nucleotide sequence analyses can reveal signatures of both historical and recent selection in the genome and may elucidate the impact that infectious disease has had during human evolution. 相似文献
19.
20.
Effects of spatially varying selection on nucleotide diversity and linkage disequilibrium: insights from deer mouse globin genes
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An important goal of population genetics is to elucidate the effects of natural selection on patterns of DNA sequence variation. Here we report results of a study to assess the joint effects of selection, recombination, and gene flow in shaping patterns of nucleotide variation at genes involved in local adaptation. We first describe a new summary statistic, Z(g), that measures the between-sample component of linkage disequilibrium (LD). We then report results of a multilocus survey of nucleotide diversity and LD between high- and low-altitude populations of deer mice, Peromyscus maniculatus. The multilocus survey included two closely linked alpha-globin genes, HBA-T1 and HBA-T2, that underlie adaptation to different elevational zones. The primary goals were to assess whether the alpha-globin genes exhibit the hallmarks of spatially varying selection that are predicted by theory (i.e., sharply defined peaks in the between-population components of nucleotide diversity and LD) and to assess whether peaks in diversity and LD may be useful for identifying specific sites that distinguish selectively maintained alleles. Consistent with theoretical expectations, HBA-T1 and HBA-T2 were characterized by highly elevated levels of diversity between populations and between allele classes. Simulation and empirical results indicate that sliding-window analyses of Z(g) between allele classes may provide an effective means of pinpointing causal substitutions. 相似文献