RESUMO
The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria provide some of the best-known case studies of strong positive selection in modern humans. I begin by reviewing JBS Haldane's initial contribution to the potential of malaria genetic resistance in humans. Further, I discuss the population genetics aspects of many of the variants, including globin, G6PD deficiency, Duffy, ovalocytosis, ABO and human leukocyte antigen variants. Many of the variants conferring resistance to malaria are 'loss-of-function' mutants and appear to be recent polymorphisms from the last 5000-10 000 years or less. I discuss estimation of selection coefficients from case-control data and make predictions about the change for S, C and G6PD-deficiency variants. In addition, I consider the predicted joint changes when the two ß-globin alleles S and C are both variable in the same population and when there is a variation for α-thalassemia and S, two unlinked, but epistatic variants. As more becomes known about genes conferring genetic resistance to malaria in humans, population genetics approaches can contribute both to investigating past selection and predicting the consequences in future generations for these variants.
Assuntos
Resistência à Doença , Genética Populacional , Malária/genética , Animais , Genética Médica , Humanos , Malária/imunologia , Malária/parasitologia , Plasmodium/fisiologiaRESUMO
Understanding the spatial structure of a population is critical for effective assessment and management. However, direct observation of spatial dynamics is generally difficult, particularly for marine mammals. California sea lions (Zalophus californianus) are polygynous pinnipeds distributed along the Pacific coast of North America. The species' range has been subdivided into three management stocks based on differences in mitochondrial DNA, but to date no studies have considered nuclear genetic variation, and thus we lack a comprehensive understanding of gene flow patterns among sea lion colonies. In light of recent population declines in the Gulf of California, Mexico, it is important to understand spatial structure to determine if declining sea lion colonies are genetically isolated from others. To define population subdivision and identify sex biases in gene flow, we analysed a 355-bp sequence of the mitochondrial DNA control region and 10 polymorphic microsatellite loci from 355 tissue samples collected from six colonies distributed along Mexican waters. Using a novel approach to estimate sex biases in gene flow, we found that male sea lions disperse on average 6.75 times more frequently than females. Analyses of population subdivision strongly suggest a pattern of isolation by distance among colonies and challenge current stock definitions. Based on these results, we propose an alternative classification that identifies three Mexican management units: Upper Gulf of California, Southern Baja Peninsula, and Upper Pacific Coast of Baja. This revised classification should be considered in future assessment and management of California sea lion populations in Mexican waters.
Assuntos
Fluxo Gênico , Genética Populacional , Leões-Marinhos/genética , Animais , Núcleo Celular/genética , DNA Mitocondrial/genética , Feminino , Frequência do Gene , Masculino , México , Repetições de Microssatélites , Polimorfismo Genético , Dinâmica PopulacionalRESUMO
Mexican and red wolves were both faced with extinction in the wild until captive populations were established more than two decades ago. These captive populations have been successfully managed genetically to minimize mean kinship and retain genetic variation. Descendants of these animals were subsequently used to start reintroduced populations, which now number about 40-50 Mexican wolves in Arizona and New Mexico and about 100 red wolves in North Carolina. The original captive Mexican wolf population was descended from three founders. Merging this lineage with two other captive lineages, each with two founders, has been successfully carried out in the captive population and is in progress in the reintroduced population. This effort has resulted in increased fitness of cross-lineage wolves, or genetic rescue, in both the captive and reintroduced populations. A number of coyote-red wolf hybrid litters were observed in the late 1990s in the reintroduced red wolf population. Intensive identification and management efforts appear to have resulted in the elimination of this threat. However, population reintroductions of both Mexican and red wolves appear to have reached numbers well below the generally recommended number for recovery and there is no current effort to re-establish other populations.
Assuntos
Cruzamento/métodos , Conservação dos Recursos Naturais/métodos , Genética Populacional , Lobos/genética , Animais , Endogamia , Linhagem , Dinâmica Populacional , Especificidade da Espécie , Estados UnidosRESUMO
The timing and pattern of reproductive barrier formation in allopatric populations has received much less attention than the accumulation of reproductive barriers in sympatry. The theory of allopatric speciation suggests that reproductive barriers evolve simply as by-products of overall genetic divergence. However, observations of enhanced premating barriers in allopatric populations suggest that sexual selection driven by intraspecific competition for mates may enhance species-specific signals and accelerate the speciation process. In a previous series of laboratory trials, we examined the strength of premating and postmating barriers in an allopatric species pair of the endangered Sonoran topminnow, Poeciliopsis occidentalis and P. sonoriensis. Behavioral observations provided evidence of asymmetrical assortative mating, while reduced brood sizes and male-biased F(1) sex ratios suggest postmating incompatibilities. Here we examine the combined effects of premating and postmating barriers on the genetic makeup of mixed populations, using cytonuclear genotype frequencies of first- and second-generation offspring. Observed genotype frequencies strongly reflect the directional assortative mating observed in behavioral trials, illustrating how isolating barriers that act earlier in the reproductive cycle will have a greater effect on total reproductive isolation and may be more important to speciation than subsequent postmating reproductive barriers.
Assuntos
Evolução Biológica , Ciprinodontiformes/genética , Genética Populacional , Hibridização Genética , Reprodução/genética , Comportamento Sexual Animal/fisiologia , Animais , Arizona , Ciprinodontiformes/fisiologia , Marcadores Genéticos/genética , Genótipo , Especificidade da EspécieRESUMO
We examined variation at a class II major histocompatibility complex (MHC) gene (DRB1) in the captive red wolf population and samples of coyotes from Texas and North Carolina. We found 4 alleles in the 48 red wolves, 8 alleles in the 10 coyotes from Texas and 15 alleles in the 29 coyotes from North Carolina. Two of the four alleles found in red wolves, Caru-2 and Caru-4, were found in both the Texas and North Carolina coyote samples. Allele Caru-1, previously found in gray wolves, was also found in the North Carolina sample. The most frequent red wolf allele, Caru-3, was not found in any of the coyote samples. However, an allele found in both the Texas and North Carolina coyote samples is only one nucleotide (one amino acid) different from this red wolf allele. Overall, it appears from examination of this MHC gene that red wolves are more closely related to coyotes than to gray wolves. There were a number of different types of evidence supporting the action of balancing selection in red wolves. Namely, there was: (i) an excess of heterozygotes compared with expectations; (ii) a higher rate of nonsynonymous than synonymous substitution for the functionally important antigen-binding site positions; (iii) an eight times higher average heterozygosity of individual amino acids at the positions identified as part of the antigen-binding site than those not associated with it; (iv) the amino acid divergence of four red wolf alleles was greater than that expected from a simulation of genetic drift; and (v) the distribution of alleles, and the distributions of amino acids at many positions were more even than expected from neutrality. Examination of the level and pattern of linkage disequilibria between pairs of sites suggest that the heterozygosity, substitution and frequencies at individual amino acids are not highly dependent upon each other.
Assuntos
Evolução Biológica , Carnívoros/genética , Variação Genética , Antígenos HLA-DR/genética , Lobos/genética , Adaptação Fisiológica , Sequência de Aminoácidos , Animais , Sequência de Bases , Genes MHC da Classe II/genética , Cadeias HLA-DRB1 , Heterozigoto , Desequilíbrio de Ligação , Dados de Sequência Molecular , Filogenia , Seleção Genética , Análise de Sequência de DNARESUMO
Twelve MHC class I exon 2 sequences were uncovered in a sample from the endangered Sacramento River winter-run Chinook salmon in the central valley of California. Phylogenetic analysis of the 12 sequences indicates that the alleles descend from two of six major allelic lineages found among four Pacific salmon species. Nine of the 12 alleles belong to an allelic lineage that began diversifying 8 million years ago, just prior to the estimated time of Chinook speciation. The most recent common ancestor of all 12 winter-run alleles is estimated to be 15 million years ago, approximately 5 million years before the radiation of the Pacific salmon species. The average nonsynonymous distance among the peptide binding-region codons of exon 2 for the 12 alleles is significantly higher than the average synonymous distance in these codons. We estimate the symmetrical overdominant selection coefficient against homozygotes for this exon to be 0.038. Thus, strong positive and balancing selection has maintained functional diversity in the peptide-binding region of the exon over millions of years and this variation has not yet been substantially eliminated by increased genetic drift due to the recent dramatic decline in abundance of this Chinook salmon population.
Assuntos
Evolução Molecular , Genes MHC Classe I , Polimorfismo Genético , Salmão/genética , Frequência do Gene , FilogeniaRESUMO
Major histocompatibility complex (MHC) genes were originally discovered because of their role in tissue rejection in mammals and have subsequently been implicated in the incidence of autoimmune diseases and resistance to infectious diseases. Here we present the first demonstration that a gene defined by molecular sequence in the fish MHC, specifically a class II locus, plays an important role in tissue rejection. This effect in the endangered Gila topminnows appears to be additive and depends on the number of MHC alleles shared between the host and the recipient fish of the scale transplants. In addition, there was lower success of scale transplants in MHC-matched individuals in a population with high microsatellite variation than in a population with low variation. This suggests that other loci, presumably other MHC loci, play a significant role in transplantation success in fishes, as they do in mammals.
Assuntos
Cyprinidae/genética , Complexo Principal de Histocompatibilidade , Transplante de Tecidos , Animais , Cyprinidae/imunologia , Variação Genética , Imunologia de TransplantesRESUMO
Bighorn sheep populations have greatly declined in numbers and distribution since European settlement, primarily because of high susceptibility to infectious diseases transmitted to them from domestic livestock. It has been suggested that low variation at major histocompatibility complex (MHC) genes, the most important genetic aspect of the vertebrate immune system, may result in high susceptibility to infectious disease. Therefore, we examined genetic polymorphism at a MHC gene (Ovca-DRB) in a large sample, both numerically and geographically, of bighorn sheep. Strikingly, there were 21 different alleles that showed extensive nucleotide and amino acid sequence divergence. In other words, low MHC variation does not appear to be the basis of the high disease susceptibility and decline in bighorn sheep. On the other hand, analysis of the pattern of the MHC polymorphism suggested that nonsynonymous substitutions predominated, especially at amino acids in the antigen-binding site. The average overall heterozygosity for the 16 amino acid positions that are part of the antigen binding site is 0.389 whereas that for the 67 amino acid positions not involved with antigen binding is 0.076. These findings imply that the diversity present in this gene is functionally significant and is, or has been, maintained by balancing selection. To examine the evolution of DRB alleles in related species, a phylogenetic analysis including other published ruminant (Bovidae and Cervidae) species, was carried out. An intermixture of sequences from bighorn sheep, domestic sheep, goats, cattle, bison, and musk ox was observed supporting trans-species polymorphism for these species. To reconcile the species and gene trees for the 104 sequences examined, 95 'deep coalescent' events were necessary, illustrating the importance of balancing selection maintaining variation over speciation events.
Assuntos
Genes MHC da Classe II , Doenças dos Ovinos , Ovinos , Sequência de Aminoácidos , Animais , Animais Selvagens , Variação Genética , Antígenos HLA-D/genética , Infecções/veterinária , Repetições de Microssatélites , Dados de Sequência Molecular , Polimorfismo Genético , Dinâmica Populacional , Alinhamento de SequênciaRESUMO
Highly variable loci can provide insight into the recognition of species, evolutionarily significant units (ESUs) and management units (MUs). In general, the ESU and MU categories are thought to be reflective of adaptive differences between them. Here we examine this premise by presenting a comprehensive examination of genetic variation for both microsatellite loci and a major histocompatibility complex (MHC) locus, thought to be of adaptive significance, in the endangered Sonoran topminnow. The extent of variation for the microsatellite loci and the MHC gene within the 13 populations of the Gila topminnow is highly correlated, suggesting that nonselective factors have played an important role in influencing variation within and between populations for the MHC locus. Therefore, using all of these loci, we found that the eight natural populations of the Gila topminnow fell into two different ESUs, one of which had four different MUs. The source of the Boyce Thompson sample, a population that was used extensively for restocking, appeared to be Monkey Spring. The source of the Watson Wash population also appeared to be Monkey Spring (or Boyce Thompson). The newly colonized Santa Cruz River population, which had the most genetic variation of any Gila topminnow population, appeared to descend primarily from Sonoita Creek populations. The Yaqui topminnow, presently considered another subspecies of the Sonoran topminnow, was very distinct for both microsatellite (only two of 25 alleles found in the Yaqui were in any of the Gila topminnow samples) and MHC alleles (nonoverlapping sets of alleles for the two groups). As a result, it appeared that the taxonomic status of the two subspecies should be re-evaluated and that full species status for Gila and Yaqui topminnows was appropriate. There was evidence for the importance of long-term selection at the MHC locus in the higher rate of nonsynonymous than synonymous substitution. In addition, there appeared to have been a duplication of the MHC locus that was present in most of the fish in six of the natural populations of the Gila topminnow.
Assuntos
Ciprinodontiformes/genética , Variação Genética , Complexo Principal de Histocompatibilidade/genética , Aminoácidos/genética , Animais , Arizona , Genética Populacional , Heterozigoto , Repetições de MicrossatélitesRESUMO
The Tiburon Island population of desert bighorn sheep has increased in size from 20 founders in 1975 to approximately 650 in 1999. This population is now the only population being used as the source stock for transplantations throughout northern Mexico. To evaluate the genetic variation in this population, we examined 10 microsatellite loci and a major histocompatibility complex (MHC) locus. The genetic variation was significantly less than found in other populations of the same subspecies in Arizona. Using a model that takes into account the effects of genetic drift on genetic distance, most of the genetic distance observed between the Tiburon population and Arizona samples could be explained. Because of the low genetic variation found in the Tiburon population, it is suggested that the Tiburon population should be supplemented with additional unrelated animals or that the transplant populations should be supplemented with unrelated animals.
Assuntos
Efeito Fundador , Variação Genética/genética , Complexo Principal de Histocompatibilidade/genética , Repetições de Microssatélites/genética , Ovinos/genética , Animais , Frequência do Gene/genética , Filogenia , Ovinos/fisiologiaRESUMO
The great expansion of population genetic data using molecular techniques now allows examination of the extent of linkage disequilibrium for many pairs of loci, each locus often with multiple alleles. The expectation-maximization (EM) algorithm for generating maximum likelihood estimates of gametic frequencies from multiallelic genotypic data is described and applied. The EM algorithm is used in desert bighorn sheep where the population size, and consequently the sample size, is often small. We calculated haplotype frequencies for all pairwise combinations of five major histocompatibility loci and three microsatellite loci in 14 populations; the performance of the algorithm is discussed. Disequilibrium values are calculated and tested for statistical significance. High levels of disequilibrium are found between all pairs of major histocompatibility complex (MHC) loci and between MHC and a linked microsatellite locus.
Assuntos
Desequilíbrio de Ligação/genética , Ovinos/genética , Alberta , Algoritmos , Animais , Genética Populacional , Funções Verossimilhança , Complexo Principal de Histocompatibilidade/genética , Repetições de Microssatélites/genética , Sudoeste dos Estados UnidosRESUMO
Supplementation of young raised at a protected site, such as a hatchery, may influence the effective population size of an endangered species. A supplementation program for the endangered winter-run chinook salmon from the Sacramento River, California, has been releasing fish since 1991. A breeding protocol, instituted in 1992, seeks to maximize the effective population size from the captive spawners by equaling their contributions to the released progeny. As a result, the releases in 1994 and 1995 appear not to have decreased the overall effective population size and may have increased it somewhat. However, mistaken use of non-winter-run chinook spawners resulted in artificial crosses between runs with a potential reduction in effective population size, and imprinting of the released fish on Battle Creek, the site of the hatchery, resulted in limiting the contribution of the released fish to the target mainstem population. Rapid genetic analysis of captured spawners and a new rearing facility on the Sacramento River should alleviate these problems and their negative effect on the effective population size in future years.
Assuntos
Densidade Demográfica , Salmão , Estações do Ano , AnimaisRESUMO
It is crucial for endangered species to retain as much genetic variation as possible to enhance recovery. Bonytail chub (Gila elegans) is one the most imperiled freshwater fish species, persisting as a declining population of large and old individuals primarily in Lake Mohave on the lower Colorado River. Establishment of a new captive broodstock from the 1981 F1 progeny of at most 10 wild fish plus any newly captured wild fish is evaluated and reviewed. The effective number of founders contributing to the 1981 F1 progeny appears quite small, varying from approximately 3.5, based on F1 allozyme data and supported by mtDNA data, to approximately 8.5, based on the original production records. Using a sample of these progeny to initiate a new broodstock further reduces the effective number of founders. With even the most optimistic evaluation of the amount of genetic variation in F1 progeny, it is obvious that including wild fish in the broodstock is essential to increase the amount of genetic variation. The approach given here could be applied to retain genetic variation in other endangered species in a captive broodstock until they have stable natural populations of adequate size.
Assuntos
Cyprinidae/genética , Variação Genética , Animais , Cruzamento , DNA Mitocondrial/análise , Feminino , Genótipo , Haplótipos , Isoenzimas/análise , Masculino , Polimorfismo Conformacional de Fita Simples , Sudoeste dos Estados UnidosRESUMO
Understanding the joint effects of gene flow and selection is one of the more important but difficult areas of evolutionary genetics. A method is presented to describe cases of gene flow-selection balance while accounting for the life history of haplodiploid social insects (eusocial Hymenoptera). A continent-island model is used to estimate gene flow rates from allele frequency data and provide variance formulae. The occurrence of unequal yet stable allele frequencies among social insect castes is explained and the usefulness of models with discrete generations for eusocial insects is explained. Gene flow and selection balance has been demonstrated for the fire ant Solenopsis invicta at two allozyme loci. This continent-island model gives results that well describe the system. Issues fundamental to the differences between X-linked and haplodiploid genetic systems and diploid genetic systems are also discussed.
Assuntos
Diploide , Genética Populacional , Haploidia , Himenópteros/genética , Seleção Genética , Comportamento Social , Animais , Formigas/genética , Feminino , Frequência do Gene , Genes de Insetos/fisiologia , Marcadores Genéticos , Masculino , Modelos Genéticos , Dinâmica Populacional , Reprodução/genéticaRESUMO
We have examined in Mexican wolves and related canids the amount of genetic variation for a class II gene in the major histocompatibility complex (MHC), thought to be part of the most important genetic basis for pathogen resistance in vertebrates. In Mexican wolves, descended from only seven founders over three lineages, there were five different alleles. These were in three phylogenetic groups, only one of which was shared between lineages. Using single stand conformation polymorphism (SSCP), we found that in samples of animals from the two polymorphic lineages, the observed heterozygosity was 0.74 and the genotypes were not different statistically from Hardy-Weinberg proportions. The Ghost Ranch lineage of Mexican wolves was monomorphic for the locus, consistent with the lower level of variation found previously for microsatellite loci and predicted from pedigree analysis. Samples of grey wolves, red wolves, and coyotes had 16 additional alleles. One Mexican wolf allele was also found in grey wolves and another allele was shared between grey and red wolves. Most of the nucleotide variation resulted in amino acid variation and there were five different amino acids found at two different positions. Only two of the 21 variable amino acid positions had solely synonymous nucleotide variation. The average heterozygosity for eight individual amino acid positions in the Mexican wolves was greater than 0.4. The estimated rate of nonsynonymous substitution was 2.5 times higher than that for synonymous substitution for the putative antigen binding site positions, indicative of positive selection acting on these positions. Examination of the known dog sequences for this locus showed that one of the Mexican wolf alleles was found in dogs and that the allele found in both grey and red wolves is also found in dogs.
Assuntos
Variação Genética/imunologia , Complexo Principal de Histocompatibilidade/genética , Lobos/genética , Lobos/imunologia , Animais , Carnívoros/genética , Carnívoros/imunologia , Cães , Genética Populacional , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , FilogeniaRESUMO
In the 1960s, the Arabian oryx was one of the most endangered species in the world, extinct in the wild and surviving in only a few captive herds. The present day population of over 2000 descends from a small number of founders and may have restricted genetic variation for important adaptive genes. We have examined the amount of genetic variation for a class II gene in the major histocompatibility complex thought to be the most important genetic basis for pathogen resistance in vertebrates. We found three very divergent alleles, which on average, differed by 24 nucleotides and 15 amino acids in the 236-bp fragment we examined. Using single-strand conformation polymorphism, we found that in a sample of 57 animals, the alleles were in Hardy-Weinberg proportions, although one allele was found only in four heterozygous individuals. The average heterozygosity for the 22 amino acid positions involved in antigen binding was 0.165, three times as high as that for the 56 amino acids not involved with antigen binding. Because the three alleles have such divergent sequences, it is likely that they may recognize peptides from quite different pathogens. As a result, maintenance of these variants should be considered as a goal in the captive breeding program of the Arabian oryx.