scholarly journals DNA Variability and Recombination Rates at X-Linked Loci in Humans

Genetics ◽  
1998 ◽  
Vol 150 (3) ◽  
pp. 1133-1141 ◽  
Author(s):  
Michael W Nachman ◽  
Vanessa L Bauer ◽  
Susan L Crowell ◽  
Charles F Aquadro
Keyword(s):  
Drosophila Melanogaster ◽  
Nucleotide Diversity ◽  
Statistical Tests ◽  
Preliminary Test ◽  
Nucleotide Variation ◽  
Recombination Rates ◽  
Average Value ◽  
Tests Of Neutrality ◽  
Neutral Equilibrium ◽  
Order Of Magnitude

Abstract We sequenced 11,365 bp from introns of seven X-linked genes in 10 humans, one chimpanzee, and one orangutan to (i) provide an average estimate of nucleotide diversity (π) in humans, (ii) investigate whether there is variation in π among loci, (iii) compare ratios of polymorphism to divergence among loci, and (iv) provide a preliminary test of the hypothesis that heterozygosity is positively correlated with the local rate of recombination. The average value for π was low (0.063%, SE = 0.036%), about one order of magnitude smaller than for Drosophila melanogaster, the species for which the best data are available. Among loci, π varied by over one order of magnitude. Statistical tests of neutrality based on ratios of polymorphism to divergence or based on the frequency spectrum of variation within humans failed to reject a neutral, equilibrium model. However, there was a positive correlation between heterozygosity and rate of recombination, suggesting that the joint effects of selection and linkage are important in shaping patterns of nucleotide variation in humans.

scholarly journals Nucleotide Variation and Recombination Along the Fourth Chromosome inDrosophila simulans

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1783-1794 ◽  
Author(s):  
Wen Wang ◽  
Kevin Thornton ◽  
J J Emerson ◽  
Manyuan Long
Keyword(s):  
Drosophila Melanogaster ◽  
Nucleotide Diversity ◽  
Local Population ◽  
Model System ◽  
Nucleotide Variation ◽  
Isofemale Lines ◽  
Fourth Chromosome ◽  
Conversion Model ◽  
Order Of Magnitude ◽  
Intron Region

AbstractThe fourth chromosome of Drosophila melanogaster and its sister species are believed to be nonrecombining and have been a model system for testing predictions of the effects of selection on linked, neutral variation. We recently examined nucleotide variation along the chromosome of D. melanogaster and revealed that a low average level of recombination could be associated with considerably high levels of nucleotide variation. In this report, we further investigate the variation along the fourth chromosome of D. simulans. We sequenced 12 gene regions evenly distributed along the fourth chromosome for a worldwide collection of 11 isofemale lines and 5 gene regions in a local population of 10 isofemale lines from South America. In contrast to predictions for regions of very low recombination, these data reveal that the variation levels in many gene regions, including an intron region of the ci gene, vary considerably along the fourth chromosome. Nucleotide diversity ranged from 0.0010 to 0.0074 in 9 gene regions interspersed with several regions of greatly reduced variation. Tests of recombination indicate that the recombination level is not as low as previously thought, likely an order of magnitude higher than that in D. melanogaster. Finally, estimates of the recombination parameters are shown to support a crossover-plus-conversion model.

scholarly journals Patterns of DNA Variability at X-Linked Loci in Mus domesticus

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1303-1316
Author(s):  
Michael W Nachman
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
House Mouse ◽  
Recombination Rate ◽  
Nucleotide Diversity ◽  
Mus Domesticus ◽  
Substantial Variation ◽  
Intraspecific Polymorphism ◽  
Recombination Rates ◽  
Interspecific Divergence

Introns of four X-linked genes (Hprt, Plp, Glra2, and Amg) were sequenced to provide an estimate of nucleotide diversity at nuclear genes within the house mouse and to test the neutral prediction that the ratio of intraspecific polymorphism to interspecific divergence is the same for different loci. Hprt and Plp lie in a region of the X chromosome that experiences relatively low recombination rates, while Glra2 and Amg lie near the telomere of the X chromosome, a region that experiences higher recombination rates. A total of 6022 bases were sequenced in each of 10 Mus domesticus and one M. caroli. Average nucleotide diversity (π) for introns within M. domesticus was quite low (π = 0.078%). However, there was substantial variation in the level of heterozygosity among loci. The two telomeric loci, Glra2 and Amg, had higher ratios of polymorphism to divergence than the two loci experiencing lower recombination rates. These results are consistent with the hypothesis that heterozygosity is reduced in regions with lower rates of recombination, although sampling of additional genes is needed to establish whether there is a general correlation between heterozygosity and recombination rate as in Drosophila melanogaster.

scholarly journals Recombination and the power of statistical tests of neutrality

1999 ◽  
Vol 74 (1) ◽  
pp. 65-79 ◽  
Author(s):  
JEFFREY D. WALL
Keyword(s):  
Balancing Selection ◽  
Statistical Tests ◽  
Neutral Theory ◽  
Population Subdivision ◽  
Test Statistics ◽  
Recombination Rates ◽  
Tests Of Neutrality ◽  
Power Studies ◽  
New Statistics ◽  
Population Recombination

Two new test statistics were constructed to detect departures from the equilibrium neutral theory that tend to produce genealogies with longer internal branches (e.g. population subdivision or balancing selection). The new statistics are based on a measure of linkage disequilibrium between adjacent pairs of segregating sites. Simulations were run to determine the power of these and previously proposed test statistics to reject an island model of geographic subdivision. Unlike previous power studies, this one uses a coalescent model with recombination. It is found that recombination rates on the order of the mutation rate substantially reduce the power of most test statistics, and that one of the new test statistics is generally more powerful than the others. Two suggestions are made for increasing the power of the statistical tests examined here. First, they can be made more powerful if critical values are obtained from simulations that condition on a lower bound for the population recombination rate. Secondly, for the same total length sequenced, power is increased if independent loci are considered instead of a single contiguous stretch.

scholarly journals Haplotype test reveals departure from neutrality in a segment of the white gene of Drosophila melanogaster.

Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1483-1490
Author(s):  
D A Kirby ◽  
W Stephan
Keyword(s):  
Drosophila Melanogaster ◽  
Statistical Tests ◽  
White Gene ◽  
Transcriptional Unit ◽  
Haplotype Blocks ◽  
Linkage Disequilibria ◽  
Intron 1 ◽  
Neutral Equilibrium ◽  
White Locus ◽  
Intron 2

Abstract Restriction map studies previously revealed extensive linkage disequilibria in the transcriptional unit of the white locus in natural Drosophila melanogaster populations. To understand the causes of these disequilibria, we sequenced a 4722-bp region of the white gene from 15 lines of D. melanogaster and 1 line of Drosophila simulans. Statistical tests applied to the entire 4722-bp region do not reject neutrality. In contrast, a test for high-frequency haplotypes ("Haplotype test") revealed an 834-bp segment, encompassing the 3' end of intron 1 to the 3' end of intron 2, in which the structure of variation deviates significantly from the predictions of a neutral equilibrium model. The variants in this 834-bp segment segregate as single haplotype blocks. We proposed that these unusually large haplotype blocks are due to positive selection on polymorphisms within the white gene, including a replacement polymorphism, Arg-->Leu, within this segment.

scholarly journals Molecular variation at the vermilion locus in geographically diverse populations of Drosophila melanogaster and D. simulans.

Genetics ◽  
1995 ◽  
Vol 140 (3) ◽  
pp. 1019-1032
Author(s):  
D J Begun ◽  
C F Aquadro
Keyword(s):  
Drosophila Melanogaster ◽  
Balancing Selection ◽  
Neutral Evolution ◽  
Crossing Over ◽  
Nucleotide Variation ◽  
Geographic Differentiation ◽  
Diverse Populations ◽  
Comparable Data ◽  
Significant Differentiation ◽  
Neutral Equilibrium

Abstract We surveyed nucleotide variation at vermilion in population samples of Drosophila melanogaster from Africa, Asia and the Americas to test the hypothesis that the vermilion gene was a target of balancing selection and to improve our understanding of geographic differentiation. Patterns of polymorphism and divergence showed no evidence for non-neutral evolution. However, the frequency spectrum of polymorphic sites in some non-African samples departed from the neutral equilibrium expectation. Furthermore, there were high levels of linkage disequilibrium in non-African samples, despite apparently high rates of crossing over in the vermilion region. In the absence of comparable data from other loci in these same population samples, we cannot determine whether the unusual patterns of variation at vermilion reflect demographic as opposed to locus-specific events. We found surprisingly high levels of differentiation at vermilion between U.S. and Congo samples of D. simulans. In light of previously published allozyme and mtDNA data that provided no evidence for significant differentiation between African and non-African D. simulans populations, the vermilion data raise the possibility that both mtDNA and allozymes have been influenced by selection.

scholarly journals Statistical Tests of Neutrality of Mutations Against Population Growth, Hitchhiking and Background Selection

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 915-925 ◽  
Author(s):  
Yun-Xin Fu
Keyword(s):  
Population Growth ◽  
Statistical Tests ◽  
Dna Polymorphisms ◽  
Background Selection ◽  
Genetic Hitchhiking ◽  
Alternative Models ◽  
Tests Of Neutrality ◽  
Rare Alleles

The main purpose of this article is to present several new statistical tests of neutrality of mutations against a class of alternative models, under which DNA polymorphisms tend to exhibit excesses of rare alleles or young mutations. Another purpose is to study the powers of existing and newly developed tests and to examine the detailed pattern of polymorphisms under population growth, genetic hitchhiking and background selection. It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, FS, is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations. Background selection gives rise to quite different polymorphic patterns than does logistic population growth or genetic hitchhiking, although all of them show excesses of rare alleles or young mutations. We show that Fu and Li's tests are among the most powerful tests against background selection. Implications of these results are discussed.

scholarly journals Multi-Locus Selection and the Structure of Variation at the white Gene of Drosophila melanogaster

Genetics ◽  
1996 ◽  
Vol 144 (2) ◽  
pp. 635-645 ◽  
Author(s):  
David A Kirby ◽  
Wolfgang Stephan
Keyword(s):  
Drosophila Melanogaster ◽  
White Gene ◽  
Transcriptional Unit ◽  
North American Population ◽  
Evolutionary Mechanisms ◽  
Locus Selection ◽  
Neutral Equilibrium ◽  
History Of ◽  
High Degree ◽  
Very High

Abstract We surveyed sequence variation and divergence for the entire 5972-bp transcriptional unit of the white gene in 15 lines of Drosophila melanogaster and one line of D. simulans. We found a very high degree of haplotypic structuring for the polymorphisms in the 3′ half of the gene, as opposed to the polymorphisms in the 5′ half. To determine the evolutionary mechanisms responsible for this pattern, we sequenced a 1612-bp segment of the white gene from an additional 33 lines of D. melanogaster from a European and a North American population. This 1612-bp segment encompasses an 834bp region of the white gene in which the polymorphisms form high frequency haplotypes that cannot be explained by a neutral equilibrium model of molecular evolution. The small number of recombinants in the 834bp region suggests epistatic selection as the cause of the haplotypic structuring, while an investigation of nucleotide diversity supports a directional selection hypothesis. A multi-locus selection model that combines features from both-hypotheses and takes the recent history of D. melanogaster into account may be the best explanation for these data.

Departure from Neutrality at the Mitochondrial NADH Dehydrogenase Subunit 2 Gene in Humans, but Not in Chimpanzees

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 409-421 ◽  
Author(s):  
Cheryl A Wise ◽  
Michaela Sraml ◽  
Simon Easteal
Keyword(s):  
Nadh Dehydrogenase ◽  
Statistical Tests ◽  
Low Frequency ◽  
Nadh Dehydrogenase Subunit ◽  
Nadh Dehydrogenase Subunit 2 ◽  
Tests Of Neutrality ◽  
Slightly Deleterious Mutations ◽  
Neutral Marker ◽  
Transmembrane Regions ◽  
Interspecific Comparisons

Abstract To test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution, nucleotide sequences were determined for the 1041 bp of the NADH dehydrogenase subunit 2 (ND2) gene in 20 geographically diverse humans and 20 common chimpanzees. Contingency tests of neutrality were performed using four mutational categories for the ND2 molecule: synonymous and nonsynonymous mutations in the transmembrane regions, and synonymous and nonsynonymous mutations in the surface regions. The following three topological mutational categories were also used: intraspecific tips, intraspecific interiors, and interspecific fixed differences. The analyses reveal a significantly greater number of nonsynonymous polymorphisms within human transmembrane regions than expected based on interspecific comparisons, and they are inconsistent with a neutral equilibrium model. This pattern of excess nonsynonymous polymorphism is not seen within chimpanzees. Statistical tests of neutrality, such as Tajima's D test, and the D and F tests proposed by Fu and Li, indicate an excess of low frequency polymorphisms in the human data, but not in the chimpanzee data. This is consistent with recent directional selection, a population bottleneck or background selection of slightly deleterious mutations in human mtDNA samples. The analyses further support the idea that mitochondrial genome evolution is governed by selective forces that have the potential to affect its use as a “neutral” marker in evolutionary and population genetic studies.

scholarly journals Nucleotide Variation at theCHALCONE ISOMERASELocus inArabidopsis thaliana

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 863-872 ◽  
Author(s):  
Helmi Kuittinen ◽  
Montserrat Aguadé
Keyword(s):  
Nucleotide Diversity ◽  
Direct Relationship ◽  
Selective Sweep ◽  
Balancing Selection ◽  
Neutral Theory ◽  
Low Frequency ◽  
The Other ◽  
Nucleotide Variation ◽  
Rapid Population Growth ◽  
History Of

AbstractAn ~1.9-kb region encompassing the CHI gene, which encodes chalcone isomerase, was sequenced in 24 worldwide ecotypes of Arabidopsis thaliana (L.) Heynh. and in 1 ecotype of A. lyrata ssp. petraea. There was no evidence for dimorphism at the CHI region. A minimum of three recombination events was inferred in the history of the sampled ecotypes of the highly selfing A. thaliana. The estimated nucleotide diversity (θTOTAL = 0.004, θSIL = 0.005) was on the lower part of the range of the corresponding estimates for other gene regions. The skewness of the frequency spectrum toward an excess of low-frequency polymorphisms, together with the bell-shaped distribution of pairwise nucleotide differences at CHI, suggests that A. thaliana has recently experienced a rapid population growth. Although this pattern could also be explained by a recent selective sweep at the studied region, results from the other studied loci and from an AFLP survey seem to support the expansion hypothesis. Comparison of silent polymorphism and divergence at the CHI region and at the Adh1 and ChiA revealed in some cases a significant deviation of the direct relationship predicted by the neutral theory, which would be compatible with balancing selection acting at the latter regions.

scholarly journals Contrasting Histories of Three Gene Regions Associated With In(3L)Payne of Drosophila melanogaster

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1565-1575 ◽  
Author(s):  
Esteban Hasson ◽  
Walter F Eanes
Keyword(s):  
Drosophila Melanogaster ◽  
Sequence Variation ◽  
Present Report ◽  
Genetic Exchange ◽  
Nucleotide Variation ◽  
Distal Breakpoint ◽  
Esterase 6 ◽  
The Common ◽  
Neutrality Tests ◽  
Hsp83 Gene

In the present report, we studied nucleotide variation in three gene regions of Drosophila melanogaster, spanning >5 kb and showing different degrees of association with the cosmopolitan inversion In(3-L)Payne. The analysis of sequence variation in the regions surrounding the breakpoints and the heat shock 83 (Hsp83) gene locus, located close to the distal breakpoint, revealed the absence of shared polymorphisms and the presence of a number of fixed differences between arrangements, indicating absence of genetic exchange. In contrast, for the esterase-6 gene region, located in the center of the inversion, we observed the presence of shared polymorphisms between arrangements suggesting genetic exchange. In the regions close to the breakpoints, the common St arrangement is 10 times more polymorphic than inverted chromosomes. We propose that the lack of recombination between arrangements in these regions coupled with genetic hitchhiking is the best explanation for the low heterozygosity observed in inverted lines. Using the data for the breakpoints, we estimate that this inversion polymorphism is around 0.36 million yr old. Although it is widely accepted that inversions are examples of balanced polymorphisms, none of the current neutrality tests including our Monte Carlo simulations showed significant departure from neutral expectations.

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