CiteULike: stevanspringer's polymorphism

Oyster sperm bindin is a combinatorial fucose lectin with remarkable intra-species diversity

Stevan Springer — 2008-07-07T03:41:38-00:00

International Journal of Developmental Biology, Vol. 52 (2008), pp. 759-768.

Sperm of the oyster, Crassostrea gigas, have ring-shaped acrosomes that, after exocytosis, bind the sperm to the egg vitelline layer. Isolated acrosomal rings contain proteins of various sizes: 35-, 48-, 63-, 75- and 88-kDa. These proteins, called bindins, have identical 24-residue signal peptides and conserved 97-residue N-terminal sequences, and they differ in mass because of the presence of between 1 and 5 tandemly repeated 134-residue fucose-binding lectin (F-lectin) domains. Southern blots suggest that oyster bindin is a single copy gene, but F-lectin repeat number and sequence are variable within and between individuals. Eight residues in the F-lectin fucose-binding groove are subject to positive diversifying selection, indicating a history of adaptive evolution at the lectin's active site. There is one intron in the middle of each F-lectin repeat, and recombination in this intron creates many combinations of repeat halves. Alternative splicing creates many additional size and sequence variants of the repeat array. Males contain full-length bindin cDNAs of all 5 possible sizes, but only one or two protein mass forms exist in each individual. Sequence analysis indicates that recombination and alternate splicing create hundreds, possibly thousands, of different bindin sequences in C. gigas. The extreme within-species sequence variation in the F-lectin sequence of oyster bindin is a novel finding; most male gamete-recognition proteins are much less variable. In experimental conditions oyster eggs have poor polyspermy blocks, and bindin diversity could be an evolutionary response by sperm to match egg receptors that have diversified to avoid being fertilized by multiple sperm.

The McDonald-Kreitman Test and Slightly Deleterious Mutations

Jane Charlesworth — 2008-05-09T23:25:21-00:00

Mol Biol Evol, Vol. 25, No. 6. (1 June 2008), pp. 1007-1015.

It is possible to estimate the proportion of substitutions that are due to adaptive evolution using the numbers of silent and nonsilent polymorphisms and substitutions in a McDonald and Kreitman-type analysis. Unfortunately, this estimate of adaptive evolution is biased downward by the segregation of slightly deleterious mutations. It has been suggested that 1 way to cope with the effects of these slightly deleterious mutations is to remove low-frequency polymorphisms from the analysis. We investigate the performance of this method theoretically. We show that although removing low-frequency polymorphisms does indeed reduce the bias in the estimate of adaptive evolution, the estimate is always downwardly biased, often to the extent that one would not be able to detect adaptive evolution, even if it existed. The method is reasonably satisfactory, only if the rate of adaptive evolution is high and the distribution of fitness effects for slightly deleterious mutations is very leptokurtic. Our analysis suggests that adaptive evolution could be quite prevalent in humans (>8%) and still not be detectable using current methodologies. Our analysis also suggests that the level of adaptive evolution has probably been underestimated, possibly substantially, in both bacteria and Drosophila. 10.1093/molbev/msn005

Extraordinary intraspecific diversity in oyster sperm bindin

GW Moy — 2008-02-12T19:03:13-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 6. (12 February 2008), pp. 1993-1998.

In free-spawning invertebrates spermegg incompatibility is a barrier to mating between species, and divergence of gamete recognition proteins (GRPs) can result in reproductive isolation. Of interest are processes that create reproductive protein diversity within species, because intraspecific variants are potentially involved in mate choice and early speciation. Sperm acrosomes of the Pacific oyster Crassostrea gigas contain the protein bindin that bonds sperm to egg during fertilization. Oyster bindin is a single-copy gene encoding a diversity of protein variants. Oyster bindins have a conserved N-terminal region followed by one to five tandem fucose-binding lectin (F-lectin) domains. These repeats have diversified by positive selection at eight sites clustered on the F-lectin's fucose binding face. Additional bindin variants result from recombination in an intron in each F-lectin repeat. Males also express alternatively spliced bindin cDNAs with one to five repeats, but typically translate only one or two isoforms into protein. Thus, positive selection, alternative splicing, and recombination can create thousands of bindin variants within C. gigas. Models of sexual conflict predict high male diversity when females are diverse and sexual conflict is strong. The amount of intraspecific polymorphism in male GRPs may be a consequence of the relative efficiency of local (molecular recognition) and global (electrical, cortical, and physical) polyspermy blocks that operate during fertilization. 10.1073/pnas.0711862105

Genetic differentiation by sexual conflict.

TI Hayashi — 2007-05-23T23:58:46-00:00

Evolution Int J Org Evolution, Vol. 61, No. 3. (March 2007), pp. 516-529.

Sexual conflict has been suggested as a general cause of genetic diversification in reproductive characters, and as a possible cause of speciation. We use individual-based simulations to study the dynamics of sexual conflict in an isolated diploid population with no spatial structure. To explore the effects of genetic details, we consider two different types of interlocus interaction between female and male traits, and three different types of intra-locus interaction. In the simulations, sexual conflict resulted in at least the following five regimes: (1) continuous coevolutionary chase, (2) evolution toward an equilibrium, (3) cyclic coevolution, (4) extensive genetic differentiation in female traits/genes only, and (5) extensive genetic differentiation in both male and female traits/genes. Genetic differentiation was hardly observed when the traits involved in reproduction were determined additively and interacted in a trait-by-trait way. When the traits interacted in a component-by-component way, genetic differentiation was frequently observed under relatively broad conditions. The likelihood of genetic differentiation largely depended on the number of loci and the type of within-locus dominance. With multiple loci per trait, genetic differentiation was often observed but sympatric speciation was typically hindered by recombination. Sympatric speciation was possible but only under restrictive conditions. Our simulations also highlight the importance of stochastic effects in the dynamics of sexual conflict.

Heterosis as an Explanation for Large Amounts of Genic Polymorphism.

R C Lewontin — 2007-03-15T20:27:43-00:00

Genetics, Vol. 88, No. 1. (January 1978), pp. 149-169.

By using both numerical and analytical approaches, we have shown that heterosis alone is not a mechanism for maintaining many alleles segregating at a locus. Even when all heterozygous are more fit than all homozygotes, the proportion of fitness arrays that will lead to a stable, feasible equilibrium of more than 6 or 7 alleles is vanishingly small. More alleles can be maintained if, in addition to heterosis, it is assumed that there is very little variation in fitness from heterozygote to heterozygote, with the ratio of mean heterosis to standard deviation of fitness among heterozygotes in the neighborhood of 10. When such conditions hold, the allelic frequency distribution and equilibrium will be very uniform, with all alleles very close to equal frequency (see PDF). It is much more likely that stable equilibria for multiple alleles will be best explained by multiple niche selection.

Recognition and Polymorphism in Host-Parasite Genetics

Steven Frank — 2007-03-15T20:12:48-00:00

Philosophical Transactions: Biological Sciences, Vol. 346, No. 1317. (1994), pp. 283-293.

Genetic specificity occurs in many host-parasite systems. Each host can recognize and resist only a subset of parasites; each parasite can grow only on particular hosts. Biochemical recognition systems determine which matching host and parasite genotypes result in resistance or disease. Recognition systems are often associated with widespread genetic polymorphism in the host and parasite populations. I describe four systems with matching host-parasite polymorphisms: plant-pathogen interactions, nuclear-cytoplasmic conflict in plants, restriction enzymes in bacterial defence against viruses, and bacterial plasmids that compete by toxin production and toxin immunity. These systems highlight several inductive problems. For example, the observed patterns of resistance and susceptibility between samples of hosts and parasites are often used to study polymorphism. The detectable polymorphism by this method may be a poor guide to the actual polymorphism and to the underlying biochemistry of host-parasite recognition. The problem of using detectable polymorphism to infer the true nature of recognition and polymorphism is exacerbated by non-equilibrium fluctuations in allele frequencies that commonly occur in host-parasite systems. Another problem is that different matching systems may lead either to low frequencies of host resistance and common parasites, or to common resistance and rare parasites. Thus low levels of host resistance or rare parasites do not imply that parasitism is an unimportant evolutionary force on host diversity. Knowledge of biochemical recognition systems and dynamical analysis of models provide a framework for analysing the widespread polymorphisms in host-parasite genetics.

Protein Polymorphism as a Phase of Molecular Evolution

Motoo Kimura — 2007-03-15T20:00:52-00:00

Nature, Vol. 229, No. 5285. (12 February 1971), pp. 467-469.

Natural Selection for Variances in Offspring Numbers: A New Evolutionary Principle

John Gillespie — 2007-03-15T18:59:02-00:00

The American Naturalist, Vol. 111, No. 981. (1977), pp. 1010-1014.

Protein Diversity from Alternative Splicing: A Challenge for Bioinformatics and Post-Genome Biology

Douglas Black — 2007-03-12T20:44:14-00:00

Cell, Vol. 103, No. 3. (27 October 2000), pp. 367-370.

Antagonistic Pleiotropy, Reversal of Dominance, and Genetic Polymorphism

James Curtsinger — 2007-03-08T19:34:46-00:00

The American Naturalist, Vol. 144, No. 2. (1994), pp. 210-228.

Conditions for polymorphism at pleiotropic loci with antagonistic effects on fitness components are investigated, under the assumptions of additivity and multiplicativity of fitness components. We show that the conditions for stable polymorphism are rather restrictive, especially with weak selection. The conditions are also very sensitive to the dominance parameters; in particular, reversal of dominance is often required for stable polymorphism. A review of biochemical mechanisms of dominance suggests that dominance reversal is not likely to be common. The conditions for maintaining genetic variation at two antagonistic and pleiotropic loci are even more restrictive than for the one-locus case. When conditions for stable polymorphism by antagonistic pleiotropy are satisfied, substantial dominance variance in one or both fitness components is expected but is seldom observed in experiments. Antagonistic pleiotropy implies stabilizing selection on the fitness components separately, which usually tends to reduce genetic variance. We conclude that, even though trade-offs in fitness components may be common, antagonistic pleiotropy probably plays a limited role in explaining the persistence of genetic variation in fitness components.

Sperm competition and the maintenance of polymorphism.

AG Clark — 2007-03-01T20:11:39-00:00

Heredity, Vol. 88, No. 2. (February 2002), pp. 148-153.

Sperm competition may occur whenever sperm from more than one male are present in the reproductive tract of the female. Studies of field-caught Drosophila reveal that a substantial fraction (80%) of females clearly have sperm from more than one male, and the figure is probably higher because only a small number of progeny are typically surveyed, so a strong skew in paternity can make multiply-mated females appear as singly mated unless appropriate models are applied. Examination of genetic variation in aspects of sperm competition has revealed some striking patterns, particularly in the implications for the maintenance of polymorphism. The magnitude of variation in sperm competitive ability is as great as that for other fitness components, and the males with the strongest displacement also appear to be the ones with the greatest positive effect on fertility. Why then does not the most competitive allele simply go to fixation? Such synergistic pleiotropy makes the polymorphism even more unexpected. Examination of patterns of competitive success of pairs of male genotypes, and of female-male interactions, demonstrate clearly that the outcome of sperm competition is not a simple property of each male. That is, sperm competitive ability of male genotypes cannot simply be ranked from best to worst. Rather, the outcome of each competitive bout depends on the particular pair of males. These results have intriguing implications for the molecular biology of genes involved in the determination of sperm competitive success, and on the opportunity for maintenance of polymorphism in those genes.

Heterozygote advantage and the maintenance of polymorphism for multilocus traits.

A Ding — 2007-03-01T20:08:16-00:00

Theor Popul Biol, Vol. 68, No. 3. (November 2005), pp. 157-166.

Explaining how polymorphism is maintained in the face of selection remains a puzzle since selection tends to erode genetic variation. Provided an infinitely large unsubdivided population and no frequency-dependance of selective values, heterozygote advantage is the text book explanation for the maintenance of polymorphism when selection acts at a diallelic locus. Here, we investigate whether this remains true when selection acts at multiple diallelic loci. We use five different definitions of heterozygote advantage that largely cover this concept for multiple loci. Using extensive numerical simulations, we found no clear associations between the presence of any of the five definitions of heterozygote advantage and the maintenance of polymorphism at all loci. The strength of the association decreases as the number of loci increases or as recombination decreases. We conclude that heterozygote advantage cannot be a general mechanism for the maintenance of genetic polymorphism at multiple loci. These findings suggest that a correlation between the number of heterozygote loci and fitness is not warranted on theoretical ground.

Statistical Tests for Detecting Positive Selection by Utilizing High-Frequency Variants

Kai Zeng — 2006-11-24T21:15:10-00:00

Genetics, Vol. 174, No. 3. (1 November 2006), pp. 1431-1439.

By comparing the low-, intermediate-, and high-frequency parts of the frequency spectrum, we gain information on the evolutionary forces that influence the pattern of polymorphism in population samples. We emphasize the high-frequency variants on which positive selection and negative (background) selection exhibit different effects. We propose a new estimator of theta (the product of effective population size and neutral mutation rate), thetaL, which is sensitive to the changes in high-frequency variants. The new thetaL allows us to revise Fay and Wu's H-test by normalization. To complement the existing statistics (the H-test and Tajima's D-test), we propose a new test, E, which relies on the difference between thetaL and Watterson's thetaW. We show that this test is most powerful in detecting the recovery phase after the loss of genetic diversity, which includes the postselective sweep phase. The sensitivities of these tests to (or robustness against) background selection and demographic changes are also considered. Overall, D and H in combination can be most effective in detecting positive selection while being insensitive to other perturbations. We thus propose a joint test, referred to as the DH test. Simulations indicate that DH is indeed sensitive primarily to directional selection and no other driving forces. 10.1534/genetics.106.061432

Polymorphisms in Human Langerin Affect Stability and Sugar Binding Activity

Eliot Ward — 2006-06-22T22:29:55-00:00

J. Biol. Chem., Vol. 281, No. 22. (2 June 2006), pp. 15450-15456.

Langerhans cells are specialized skin dendritic cells that take up and degrade antigens for presentation to the immune system. Langerin, a cell surface C-type lectin of Langerhans cells, can be internalized and accumulates in Birbeck granules, subdomains of the endosomal recycling compartment that are specific to Langerhans cells. Langerin binds and mediates uptake and degradation of glycoconjugates containing mannose and related sugars. Analysis of the human genome has identified three single nucleotide polymorphisms that result in amino acid changes in the carbohydrate-recognition domain of langerin. The effects of the amino acid changes on the activity of langerin were examined by expressing each of the polymorphic forms. Expression of full-length versions of the four common langerin haplotypes in fibroblasts revealed that all of these forms can mediate endocytosis of neoglycoprotein ligands. However, sugar binding assays and differential scanning calorimetry performed on fragments from the extracellular domain showed that two of the amino acid changes reduce the affinity of the carbohydrate-recognition domain for mannose and decrease the stability of the extracellular domain. In addition, analysis of sugar binding by langerin containing the rare W264R mutation, previously identified in an individual lacking Birbeck granules, shows that this mutation abolishes sugar binding activity. These findings suggest that certain langerin haplotypes may differ in their binding to pathogens and thus might be associated with susceptibility to infection. 10.1074/jbc.M511502200

Statistical analysis of DNA polymorphism.

F Tajima — 2006-03-01T05:39:17-00:00

Jpn J Genet, Vol. 68, No. 6. (December 1993), pp. 567-595.

A large amount of genetic variation can be maintained in natural populations. In order to understand the mechanism maintaining genetic variation, we must first estimate the amount of genetic variation. There are two measures for estimating the amount of DNA polymorphism, i.e., the average number of pairwise nucleotide differences and the number of segregating sites among a sample of DNA sequences. Using these two measures, we can test the neutral mutation-random drift hypothesis (the neutral theory). The expectation of the amount of DNA polymorphism has been studied under several models, including population subdivision, change in population size, and natural selection. When a population is subdivided, a large amount of DNA polymorphism can be maintained in the population if the migration rates among subpopulations are small. In this case the amount of DNA polymorphism in the subpopulation with lower migration rate is expected to be smaller than that of higher migration rate. When the population size changes, the number of segregating sites changes more rapidly than does the average number of nucleotide differences. When purifying selection is operating, the number of segregating sites is more strongly affected by the existence of deleterious mutants than is the average number of nucleotide differences. On the other hand, when balancing selection is operating, the effect of the selection on the average number of nucleotide differences is larger than that on the number of segregating sites. A mutant under natural selection affects the amount of DNA polymorphism at linked sites (hitchhiking effect). DNA sequences are not random sequences and there may be conservative and variable regions in them. A statistical method for determining the window size and for finding nonrandom regions in the sequence is also presented.

A scan for positively selected genes in the genomes of humans and chimpanzees.

R Nielsen — 2005-10-26T04:35:38-00:00

PLoS Biol, Vol. 3, No. 6. (June 2005)

Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.