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Genetic variation of aldehyde dehydrogenase has been demonstrated in catarrhine primates. The results are in accordance with the formal genetic interpretation: three alleles, AldDH1, AldDH2, AldDH3, at the gene locus AldDH. Obviously, the allele AldDH1 has undergone fixation in Homo and Hylobates, the allele AldDH2 in Macaca and Papio, and the allele AldDH3 in Cercopithecus.
To study transmission patterns of Pneumocystis carinii pneumonia (PCP) in persons with AIDS, we evaluated P. carinii isolates from patients in five U.S. cities for variation at two independent genetic loci, the mitochondrial large subunit rRNA and dihydropteroate synthase. Fourteen unique multilocus genotypes were observed in 191 isolates that were examined at both loci. Mixed infections, accounting for 17.8% of cases, were associated with primary PCP. Genotype frequency distribution patterns varied by patients' place of diagnosis but not by place of birth. Genetic variation at the two loci suggests three probable characteristics of transmission: that most cases of PCP do not result from infections acquired early in life, that infections are actively acquired from a relatively common source (humans or the environment), and that humans, while not necessarily involved in direct infection of other humans, are nevertheless important in the transmission cycle of P. carinii f. sp. hominis.
Local populations of herbivore species that display variation in host plant use are subject to natural selection for improved ability to use their own host species. Since natural selection changes the frequency of alleles that control host use, genetic variation in growth performance on host plants may change with each generation of selection. Therefore, within-population variations in the ability to use different hosts may reflect past selective forces. The present study reports the genetic variation in growth performance in a population of the herbivorous ladybird beetle, Epilachna vigintioctomaculata Motschulsky (Coccinellidae, Epilachninae) on both the normal host and a novel host. The present study found higher heritabilities for growth performance on the novel host than the normal host. The difference in heritabilities was caused by smaller among-family variance components on the normal host compared to those on the novel host. The results are compatible with the view that natural selection, which improved the ability of the population to use a particular host plant, has reduced genetic variation within that population in the ability to use that host plant. The pattern of reduced genetic variation in a population reared on the normal host observed in the present study is compared with that in another population, which showed local adaptation in the use of its own host plant. The effect of natural selection on differing host plant use on within-population genetic variation is discussed.
Genetic variation of hepatitis C virus was assessed. We prepared RNA fractions from 21 patients' sera which were positive for hepatitis C virus RNA, synthesized their cDNAs, and amplified fragments, 406 base pairs, encoding a putative core protein, by polymerase chain reaction. One of them, N 15, was cloned and sequenced. N 15 showed 92.4% homology at the nucleotide level and 97.0% homology at the amino acid level compared with HC-J 1 which is the first isolated clone in Japan and similar to that isolated in USA. By restriction fragment length polymorphisms analysis, 14 out of 21 patients (66.7%) showed the same pattern as N 15. No patients showed the pattern of HC-J 1. We could not find a correlation between the genetic variation and clinical features of hepatitis C virus infection. These results indicate that the region, which encodes the core protein and is believed to be relatively conserved in hepatitis C virus genome, has several variations at the nucleotide level, and the major part of hepatitis C virus in Okayama district is different from HC-J 1 and the USA clone.
Chinese indigenous pig breeds are recognized as an invaluable component of the world's pig genetic resources and are divided traditionally into six types. Twenty-six microsatellite markers recommended by the FAO (Food and Agriculture Organization) and ISAG (International Society of Animal Genetics) were employed to analyze the genetic diversity of 18 Chinese indigenous pig breeds with 1001 individuals representing five types, and three commercial breeds with 184 individuals. The observed heterozygosity, unbiased expected heterozygosity and the observed and effective number of alleles were used to estimate the genetic variation of each indigenous breed. The unbiased expected heterozygosity ranged between 0.700 (Mashen) and 0.876 (Guanling), which implies that there is an abundant genetic variation stored in Chinese indigenous pig breeds. Breed differentiation was shown by fixation indices (FIT, FIS, and FST). The FST per locus varied from 0.019 (S0090) to 0.170 (SW951), and the average FST of all loci was 0.077, which means that most of the genetic variation was kept within breeds and only a little of the genetic variation exists between populations. The Neighbor-Joining tree was constructed based on the Nei DA (1978) distances and one large cluster with all local breeds but the Mashen breed, was obtained. Four smaller sub-clusters were also found, which included two to four breeds each. These results, however, did not completely agree with the traditional type of classification. A Neighbor-Joining dendrogram of individuals was established from the distance of -ln(proportions of shared alleles); 92.14% of the individuals were clustered with their own breeds, which implies that this method is useful for breed demarcation. This extensive research on pig genetic diversity in China indicates that these 18 Chinese indigenous breeds may have one common ancestor, helps us to better understand the relative distinctiveness of pig genetic resources, and will assist in developing a national plan for the conservation and utilization of Chinese indigenous pig breeds.
The genetic variations of Lycoris radiata var. radiata, a completely sterile triploid from Japan, were examined by comparing the nucleotide sequences of genomic DNA regions in 11 triploid strains sampled from Japan and four triploid strains sampled from China, and in two diploid strains of Lycoris radiata var. pumila, which is endemic to China and fertile. For this purpose, two genes were analyzed, the lectin gene in the nuclear genome and the maturase gene in the chloroplast genome. A clear genetic constancy was observed in their DNA nucleotide sequences. For both genes, completely identical nucleotide sequences were detected in the 11 Japanese and four Chinese triploid strains and also between the two Chinese diploid strains. However, some genetic variations were observed between the Japanese and Chinese triploid strains, and between the triploid and diploid strains. These results are consistent with the findings obtained from previous chromosome karyotype analyses and allozyme analyses. In addition, in our preliminary FISH analysis of the physical mapping of the rRNA gene family, the 18S-5.8S-26S rRNA and 5S rRNA loci were localized on six and four chromosomes, respectively. Regarding the 18S-5.8S-26S rRNA loci, two were associated with two SAT chromosomes. The remaining four were distinguished by having no secondary constriction. Localization of 5S rRNA loci to chromosome spreads revealed three sites on the proximal part of the long arm of three acrocentric chromosomes and one site on the distal part of the long arm of the SAT chromosome; the latter site was juxtaposed to the 18S-5.8S-26S rRNA loci. These findings indicate that L. radiata var. radiata is not a typical autotriploid. The present paper discusses the possible origin of L. radiata var. radiata from a diploid variety of L. radiata var. pumila, based on the molecular cytogenetic analysis and DNA sequence analysis.
Genetic variations are playing an increasing role in drug discovery, particularly in disease-specific drug target identification and in drug candidate profiling to predict drug response in genetically heterogeneous patient populations. Recently, genetic studies have successfully contributed to the identification of new susceptibility genes, disease mechanisms and potentially novel disease-specific drug targets for common diseases such as Type II diabetes, Crohn's disease, asthma and osteoporosis. Numerous variants of cytochrome P450 enzymes and the pregnane X receptor, recently associated with protein expression and altered catalytic activities, may prove to be of use in the future in drug candidate profiling.
The evolution of morphological modularity through the sequestration of pleiotropy to sets of functionally and developmentally related traits requires genetic variation in the relationships between traits. Genetic variation in relationships between traits can result from differential epistasis, where epistatic relationships for pairs of loci are different for different traits. This study maps relationship quantitative trait loci (QTLs), specifically QTLs that affect the relationship between individual mandibular traits and mandible length, across the genome in an F2 intercross of the LG/J and SM/J inbred mouse strains (N = 1045). We discovered 23 relationship QTLs scattered throughout the genome. All mandibular traits were involved in one or more relationship QTL. When multiple traits were affected at a relationship QTL, the traits tended to come from a developmentally restricted region of the mandible, either the muscular processes or the alveolus. About one-third of the relationship QTLs correspond to previously located trait QTLs affecting the same traits. These results comprise examples of genetic variation necessary for an evolutionary response to selection on the range of pleiotropic effects.
Indirect ecological effects (IEEs) are widespread and often as strong as the phenotypic effects arising from direct interactions in natural communities. Indirect effects can influence competitive interactions, and are thought to be important selective forces. However, the extent that selection arising from IEEs results in long-term evolutionary change depends on genetic variation underlying the phenotypic response-that is, a genotype-by-IEE interaction. We provide the first data on genetic variation in the response of traits to an IEE, and illustrate how such genetic variation might be detected and analysed. We used a model tri-trophic system to investigate the effect of host plants on two populations of predatory ladybirds through a clonal aphid herbivore. A split-family experimental design allowed us to estimate the effects of aphid host plant on ladybird traits (IEE) and the extent of genetic variation in ladybird predators for response to these effects (genotype-by-indirect environmental effect interaction). We found significant genetic variation in the response of ladybird phenotypes to the indirect effect of host plant of their aphid prey, demonstrating the potential for evolutionary responses to selection arising from the prey host.
The extent and distribution of genetic variation in wild sorghum (Sorghum bicolor ssp. verticilliflorum (L.) Moench) collected from five different geographical regions in Ethiopia were analyzed using random amplified polymorphic DNA (RAPD) markers for 93 individuals representing 11 populations. Nine decamer primers generated a total of 83 polymorphic bands with 8-12 bands per primer and a mean of 9 bands across the 93 individuals. The amount of genetic variation among the populations (H = 0.37) and among the geographical region (H = 0.44) was low to moderate, despite the high degree of polymorphic bands per primer. Similarly, the mean genetic distance (0.08) among populations as well as among regions of origin (0.04) of the population was found to be low. The low genetic variation may be due to the reduced population size of the wild sorghum in Ethiopia because of habitat change. Partitioning of the genetic variation into between and within the population as well as between and within the regions of origin revealed that 75% and 88% of the variation was found within the populations and within the regions, respectively. Cluster analysis of genetic distance estimates further confirmed low level of differentiation of wild sorghum populations both on population and regional bases. The implications of the results for genetic conservation purposes are discussed.
Studies using the classical twin design often conclude that most genetic variation underlying personality is additive in nature. However, studies analyzing only twins are very limited in their ability to detect non-additive genetic variation and are unable to detect sources of variation unique to twins, which can mask non-additive genetic variation. The current study assessed 9672 MZ and DZ twin individuals and 3241 of their siblings to investigate the environmental and genetic architecture underlying eight dimensions of personality: four from Eysenck's Personality Questionnaire and four from Cloninger's Temperament and Character Inventory. Broad-sense heritability estimates from best-fitting models were two to three times greater than the narrow-sense heritability estimates for Harm Avoidance, Novelty Seeking, Reward Dependence, Persistence, Extraversion, and Neuroticism. This genetic non-additivity could be due to dominance, additive-by-additive epistasis, or to additive genetic effects combined with higher-order epistasis. Environmental effects unique to twins were detected for both Lie and Psychoticism but accounted for little overall variation. Our results illustrate the increased sensitivity afforded by extending the classical twin design to include siblings, and may provide clues to the evolutionary origins of genetic variation underlying personality.
Amplification of the esterase B1 gene is responsible for insecticide resistance in the mosquito Culex quinquefasciatus. We used a mating scheme to isolate chromosomes carrying amplified esterase genes from a long-selected laboratory strain (Tem-R) to determine whether observed variation in esterase activity had a genetic basis. The amplified esterase genes segregated as a block and a possible newly arisen esterase B1 copy-number variant was found among the progeny of females which carried amplified B1 genes on only one homologue. A quantitative genetic analysis found significant genetic variation of esterase activity among families which carried different amplification-bearing chromosomes from the Tem-R strain. Esterase B1 copy-number variation among these Tem-R chromosomes is the most likely basis for the observed genetic variation in esterase activity.
The mechanisms regulating thymic involution are unclear. In inbred mouse strains the rate of thymic involution and the function of the hematopoietic stem cell (HSC) compartment are subject to quantitative genetic variation. We have shown previously that transforming growth factor-beta2 (TGF-beta2) is a genetically determined positive regulator of HSCs. Here, we demonstrate that genetic variation in the rate of thymic involution correlates with genetic variation in the responsiveness of hematopoietic stem and progenitor cells to TGF-beta2. Corroborating these correlations, thymic cellularity and peripheral naive T-cell frequency were higher in old Tgfb2+/- mice than in wild-type littermates. The frequency of early T-cell precursors was increased in Tgfb2+/- mice, suggesting that TGF-beta2 affects the earliest stages of T-cell development in old mice. Reciprocal transplantation experiments indicated that TGF-beta2 expressed both in the (micro)environment and in the hematopoietic system can accelerate thymic involution; however, the age of the stem cells appeared irrelevant. Thus, although thymic involution is largely determined by the aged environment, TGF-beta2 plays a major modulatory role that is subject to genetic variation and is possibly mediated through its regulatory effects on early hematopoiesis.
BACKGROUND: Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation (inactivation) of mercaptopurine, azathioprine, and thioguanine, and exhibits genetic variation. About 11% of Caucasians have intermediate TPMT activity because of heterozygosity, and about 1 in 300 inherits TPMT deficiency as an autosomal codominant trait. If patients who have intermediate or deficient TPMT activity receive the standard dose of thiopurine medications, they can accumulate excessive thiopurine nucleotides in hematopoietic tissue, which could lead to severe and possibly fatal myelosuppression. There is very little information about TPMT genetic variation among Asian populations. We investigated the frequency of TPMT genetic variation among Thai children with acute leukemia. PROCEDURE: Fresh whole blood was obtained from 75 Thai children with acute leukemia at the time of remission. Genomic DNA was isolated from total peripheral white blood cells. We performed polymerase chain reaction (PCR) to detect 3 types of variant of the human TPMT gene. RESULTS: Among 75 patients, the frequency of heterozygotes for the TPMT gene among Thai children with acute leukemia was approximately 11%. However, the TPMT*3C was the only variant TPMT allele found among Thai children. This is different from the North American Caucasian populations, in which TPMT*3A is the predominant variant allele, and TPMT*3C is rare (approximately 5% of variant alleles). CONCLUSIONS: There is no difference in the frequency of this genetic variation between Asian and North American Caucasian populations. Determination of the TPMT genotype by PCR method before antileukemic therapy is practical and may have clinical relevance. This knowledge could be applied towards organ transplant recipients who require these medications for immunosuppression.
The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.
Magnolia sieboldii ssp. japonica, distributed mainly in western Japan, is restricted to high elevation areas (1000-2000 m above sea level) and usually forms small isolated populations. Four microsatellite loci were assayed for 19 populations from six regions spanning the range of distribution, and the levels and distribution of genetic variation were estimated. All four loci were variable, with a total of 39 alleles, but the overall level of microsatellite genetic variation was low, especially compared with a related species, M. obovata. Genetic structure in M. sieboldii was characterised by low intrapopulational genetic variation (A = 3.74 and H(o) = 0.366 on average) and high genetic differentiation even among regional populations. Highly significant isolation-by-distance (IBD) models at the short distance were detected. Genetic drift and limited gene flow was considered to be important in determining the genetic structure within regions. Total genetic differentiation was remarkably high (F(ST) = 0.488 and R(ST) = 0.538), suggesting genetic barriers among regions. Neighbour-joining dendrograms relating the 19 populations, and further analysis on the IBD models, revealed that a stepwise mutation model was more suited than an infinite allele model to explain the genetic differentiation among regions. It is suggested that mutation at microsatellite loci might be influential in generating the genetic differentiation among regions. These results showed the potential of hypervariable microsatellite loci to evaluate the effects of genetic drift and population isolation within regions, and to detect genetic distinctiveness, in spite of the loss of overall genetic variation in M. sieboldii.
The effect of a population's location on the landscape on genetic variation has been of interest to population genetics for more than half a century. However, most studies do not consider broadscale biogeography when interpreting genetic data. In this study, we propose an operational definition of a peripheral population, and then explore whether peripheral populations of Canada lynx (Lynx canadensis) have less genetic variation than core populations at nine microsatellite loci. We show that peripheral populations of lynx have fewer mean numbers of alleles per population and lower expected heterozygosity. This is surprising, given the lynx's capacity to move long distances, but can be explained by the fact that peripheral populations often have smaller population sizes, limited opportunities for genetic exchange and may be disproportionately affected by ebbs and flows of species' geographical range.
Quantitative genetic variation in behavioral response to the odorant, benzaldehyde, was assessed among a sample of 43 X and 35 third chromosomes extracted from a natural population and substituted into a common inbred background. Significant genetic variation among chromosome lines was detected. Heritability estimates for olfactory response, however, were low, as is typical for traits under natural selection. Furthermore, the loci affecting naturally occurring variation in olfactory response to benzaldehyde were not the same in males and females, since the genetic correlation between the sexes was low and not significantly different from zero for the chromosome 3 lines. Competitive fitness, viability and fertility of the chromosome 3 lines were estimated using the balancer equilibrium technique. Genetic correlations between fitness and odor-guided behavior were not significantly different from zero, suggesting the number of loci causing variation in olfactory response is small relative to the number of loci causing variation in fitness. Since different genes affect variation in olfactory response in males and females, genetic variation for olfactory response could be maintained by genotype x sex environment interaction. This unusual genetic architecture implies that divergent evolutionary trajectories for olfactory behavior may occur in males and females.