Patterns Of DNA Sequence Variation Research Articles

Clinal Variation in phyB2, a Candidate Gene for Day-Length-Induced Growth Cessation and Bud Set, Across a Latitudinal Gradient in European Aspen (Populus tremula)

The initiation of growth cessation and dormancy represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees. The most important environmental cue regulating the initiation of dormancy is a shortening of the photoperiod and phytochrome genes have been implicated in short-day-induced bud set and growth cessation in Populus. We characterized patterns of DNA sequence variation at the putative candidate gene phyB2 in 4 populations of European aspen (Populus tremula) and scored single-nucleotide polymorphisms in an additional 12 populations collected along a latitudinal gradient in Sweden. We also measured bud set from a subset of these trees in a growth chamber experiment. Buds set showed significant clinal variation with latitude, explaining approximately 90% of the population variation in bud set. A sliding-window scan of phyB2 identified six putative regions with enhanced population differentiation and four SNPs showed significant clinal variation. The clinal variation at individual SNPs is suggestive of an adaptive response in phyB2 to local photoperiodic conditions. Three of four SNPs showing clinal variation were located in regions with excessive genetic differentiation, demonstrating that searching for regions of high genetic differentiation can be useful for identifying sites putatively involved in local adaptation.

The importance of species identity in the biocontrol process: identifying the subspecies of Acacia nilotica (Leguminosae: Mimosoideae) by genetic distance and the implications for biological control

AbstractAims A molecular genetic distance study has been used in an initial survey to identify subspecies and genotypes of the weed Acacia nilotica in Australia, information needed to find suitable biocontrol agents. We use patterns of DNA sequence variation (in two DNA fragments) from each of the nine described subspecies of Acacia nilotica (L.) Delile (Leguminosae: Mimosoideae) that is to determine their genetic similarity, to verify if the Australian populations are A. nilotica ssp. indica (Benth.) Brenan, and to establish if any other subspecies are present in Australia.Location Australia and southern Africa through the Arabian peninsular to the Indo‐Pakistan subcontinent.Methods Representative specimens from the global distribution of the nine A. nilotica subspecies were sourced primarily from herbaria sheet specimens where available, and secondarily from field collections. These specimens together with related outgroups from Mimosoideae were genetically analysed using the DNA fragments trnL and internal transcribed spacer one (ITS1). We calculated a similarity index as set out in paup* using upgma (Unweighted Pair‐Group Method Arithmetic average) methods to cluster taxa to produce a genetic distance phenogram.Results Sequence results from ITS1 and trnL DNA fragments identified seven of the described subspecies of A. nilotica. Acacia nilotica ssp. cupressiformis (J. Stewart) Ali & Faruqi and A. nilotica ssp. adstringens (Schumach. & Thonn.) Roberty were not found to be genotypically distinct from A. nilotica ssp. indica and A. nilotica ssp. nilotica, respectively, based on the two DNA fragments. Subspecific ITS1 genotypes were geographically distributed similarly to previous reports that were based on morphology, with the exception that the hemispherica ITS1 genotype also occurred in Somalia. We confirmed that the Australian A. nilotica populations are mostly comprised of subspecies indica, but in addition, some individuals were found to be genetically identical to an unidentified Pakistan genotype not previously reported as occurring in Australia.Main conclusions Australian A. nilotica populations originated from India and Pakistan and we recommend further analysis to determine the complete genetic diversity profile and origins of the Australian populations. We highlight the importance of determining any hybridization between Australian populations of A. nilotica and native subgenus Acacia species. This study demonstrates the importance of genotyping weed species targeted for biocontrol and/or listed host specificity test species that may be easily misidentified. Biocontrol practitioners can justify genetic studies by considering the costs should a project fail through misidentification.

Contrasting Effects of Natural Selection on Human and Chimpanzee CC Chemokine Receptor 5

Human immunodeficiency virus type 1 (HIV-1) evolved via cross-species transmission of simian immunodeficiency virus (SIVcpz) from chimpanzees (Pan troglodytes). Chimpanzees, like humans, are susceptible to infection by HIV-1. However, unlike humans, infected chimpanzees seldom develop immunodeficiency when infected with SIVcpz or HIV-1. SIVcpz and most strains of HIV-1 require the cell-surface receptor CC chemokine receptor 5 (CCR5) to infect specific leukocyte subsets, and, subsequent to infection, the level of CCR5 expression influences the amount of HIV-1 entry and the rate of HIV-1 replication. Evidence that variants in the 5' cis-regulatory region of CCR5 (5'CCR5) affect disease progression in humans suggests that variation in CCR5 might also influence the response of chimpanzees to HIV-1/SIVcpz. To determine whether patterns of genetic variation at 5'CCR5 in chimpanzees are similar to those in humans, we analyzed patterns of DNA sequence variation in 37 wild-born chimpanzees (26 P. t. verus, 9 P. t. troglodytes, and 2 P. t. schweinfurthii), along with previously published 5'CCR5 data from 112 humans and 50 noncoding regions in the human and chimpanzee genomes. These analyses revealed that patterns of variation in 5'CCR5 differ dramatically between chimpanzees and humans. In chimpanzees, 5'CCR5 was less diverse than 80% of noncoding regions and was characterized by an excess of rare variants. In humans, 5'CCR5 was more diverse than 90% of noncoding regions and had an excess of common variants. Under a wide range of demographic histories, these patterns suggest that, whereas human 5'CCR5 has been subject to balancing selection, chimpanzee 5'CCR5 has been influenced by a selective sweep. This result suggests that chimpanzee 5'CCR5 might harbor or be linked to functional variants that influence chimpanzee resistance to disease caused by SIVcpz/HIV-1.

DNA Sequence Variation and Haplotype Structure of the ICAM1 and TNF Genes in 12 Ethnic Groups of India Reveal Patterns of Importance in Designing Association Studies

We have examined the patterns of DNA sequence variation in and around the genes coding for ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India. We aimed to (a) quantify the nature and extent of the variation, and (b) analyse the observed patterns of variation in relation to population history and ethnic background. At the ICAM1 and TNF loci, respectively, the total numbers of SNPs that were detected were 28 and 12. Many of these SNPs are not shared across ethnic groups and are unreported in the dbSNP or TSC databases, including two fairly common non-synonymous SNPs at positions 13487 and 13542 in the ICAM1 gene. Conversely, the TNF-376A SNP that is reported to be associated with susceptibility to malaria was not found in our study populations, even though some of the populations inhabit malaria endemic areas. Wide between-population variation in the frequencies of shared SNPs and coefficients of linkage disequilibrium have been observed. These findings have profound implications in case-control association studies.

Sequencing Complex Diseases With HapMap

Determining the patterns of DNA sequence variation in the human genome is a useful first step toward identifying the genetic basis of a common disease. A haplotype map (HapMap), aimed at describing these variation patterns across the entire genome, has been recently developed by the International HapMap Consortium. In this article, we present a novel statistical model for directly characterizing specific sequence variants that are responsible for disease risk based on the haplotype structure provided by HapMap. Our model is developed in the maximum-likelihood context, implemented with the EM algorithm. We perform simulation studies to investigate the statistical properties of this disease-sequencing model. A worked example from a human obesity study with 155 patients was used to validate this model. In this example, we found that patients carrying a haplotype constituted by allele Gly16 at codon 16 and allele Gln27 at codon 27 genotyped within the beta2AR candidate gene display significantly lower body mass index than patients carrying the other haplotypes. The implications and extensions of our model are discussed.

Genetic diversity and management of Nearctic rock ptarmigan (Lagopus mutus)

Though the rock ptarmigan, Lagopus mutus (Montin, 1776), is a relatively common breeding bird in arctic regions worldwide, several Nearctic insular populations have become extinct or threatened in the past 250 years. In this study, we use patterns of DNA sequence variation in the mitochondrial control region and a nuclear intron (GAPDH) to reexamine the evolutionary history of Nearctic rock ptarmigan populations as a basis for conservation and management. The extent of genetic diversity within currently recognized subspecies varies widely, with many nonmigratory insular subspecies genetically invariant and continental subspecies moderately diverse. Our analyses suggest at least six evolutionarily significant units (ESUs) in the Nearctic and Iceland, four of which correspond to recognized subspecies: Lagopus mutus evermanni (Elliot, 1896) on Attu I., Alaska, Lagopus mutus welchi (Brewster, 1885) on Newfoundland, Lagopus mutus rupestris (Gmelin, 1789) in the Canadian Arctic, and Lagopus mutus islandorum (Faber, 1822) on Iceland. A fifth ESU comprises three central Aleutian subspecies. The remaining subspecies of the Aleutian archipelago, along with Lagopus mutus nelsoni (Stejneger, 1884) of mainland Alaska and Lagopus mutus captus (Peters, 1934) of Ellesmere I., Nunavut, constitute a sixth ESU, which we further subdivide into three management units based on patterns of genetic substructuring and geographic barriers to immigration.

Natural Selection and Molecular Evolution in PTC, a Bitter-Taste Receptor Gene

The ability to taste phenylthiocarbamide (PTC) is a classic phenotype that has long been known to vary in human populations. This phenotype is of genetic, epidemiologic, and evolutionary interest because the ability to taste PTC is correlated with the ability to taste other bitter substances, many of which are toxic. Thus, variation in PTC perception may reflect variation in dietary preferences throughout human history and could correlate with susceptibility to diet-related diseases in modern populations. To test R. A. Fisher's long-standing hypothesis that variability in PTC perception has been maintained by balancing natural selection, we examined patterns of DNA sequence variation in the recently identified PTC gene, which accounts for up to 85% of phenotypic variance in the trait. We analyzed the entire coding region of PTC (1,002 bp) in a sample of 330 chromosomes collected from African (n=62), Asian (n=138), European (n=110), and North American (n=20) populations by use of new statistical tests for natural selection that take into account the potentially confounding effects of human population growth. Two intermediate-frequency haplotypes corresponding to "taster" and "nontaster" phenotypes were found. These haplotypes had similar frequencies across Africa, Asia, and Europe. Genetic differentiation between the continental population samples was low (FST=0.056) in comparison with estimates based on other genes. In addition, Tajima's D and Fu and Li's D and F statistics demonstrated a significant deviation from neutrality because of an excess of intermediate-frequency variants when human population growth was taken into account (P<.01). These results combine to suggest that balancing natural selection has acted to maintain "taster" and "nontaster" alleles at the PTC locus in humans.

The International HapMap Project.

The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

Inferring human history: clues from Y-chromosome haplotypes.

DNA molecules are organic elements of information storage imbued with imperfect copying processes. Thus, they are fundamental repositories of an organism’s evolutionary history. The field of human molecular evolution is predicated on the concept that patterns of DNA sequence variation in living populations encode aspects of human heritage shaped by a constellation of evolutionary influences. The framework of genetic variability in the genome reflects both evolutionary adaptive processes that are locus-specific and population-level forces that affect all the components of the genome equally. Genetic research often focuses on distinguishing inconsistencies in patterns of variation between genomic regions to help bridge the gap between particular genes and traits, including matters of function and malfunction. Alternatively, genomic DNA is also an archive of those aspects of human evolutionary processes reflective of population-level forces like drift, subdivision, size fluctuation, and migration. By studying the degree of genetic molec

Complex High-Resolution Linkage Disequilibrium and Haplotype Patterns of Single-Nucleotide Polymorphisms in 2.5 Mb of Sequence on Human Chromosome 21

One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

Patterns of DNA sequence variation suggest the recent action of positive selection in the janus-ocnus region of Drosophila simulans.

Levels of nucleotide polymorphism in three paralogous Drosophila simulans genes, janusA (janA), janusB (janB), and ocnus (ocn), were surveyed by DNA sequencing. The three genes lie in tandem within a 2.5-kb region of chromosome arm 3R. In a sample of eight alleles from a worldwide distribution we found a significant departure from neutrality by several statistical tests. The most striking feature of this sample was that in a 1.7-kb region containing the janA and janB genes, 30 out of 31 segregating sites contained variants present only once in the sample, and 29 of these unique variants were found in the same allele. A restriction survey of an additional 28 lines of D. simulans revealed strong linkage disequilibrium over the janA-janB region and identified six more alleles matching the rare haplotype. Among the rare alleles, the level of DNA sequence variation was typical for D. simulans autosomal genes and showed no departure from neutrality. In addition, the rare haplotype was more similar to the D. melanogaster sequence, indicating that it was the ancestral form. These results suggest that the derived haplotype has risen to high worldwide frequency relatively recently, most likely as a result of natural selection.

Patterns of DNA sequence variation in chromosomally recognized taxa of Anopheles gambiae: evidence from rDNA and single-copy loci.

Patterns of DNA sequence variation in the ribosomal DNA (rDNA) second internal transcribed spacer (ITS2) and five unlinked single-copy nuclear loci were examined for evidence of reproductive isolation among four chromosomally recognized taxa of Anopheles gambiae from West Africa: Savanna, Bamako, Mopti and Forest, as well as sibling species An. arabiensis and An. merus. Included among the single-copy loci were three sequence-tagged random amplified polymorphic DNA (RAPD) loci, two of which (R15 and R37) had been reported as discriminating between Mopti and other chromosomal forms. Each of the five single-copy sequences were highly polymorphic in most samples. However, the R15 and R37 loci had no diagnostic value, and therefore are not recommended as tools in recognition of field-collected An. gambiae chromosomal forms. Although pairwise comparisons between species generally revealed significant levels of differentiation at all five loci, variation was not partitioned by chromosomal form within An. gambiae at any single-copy locus examined. The few exceptions to these trends appear related to a location either inside or nearby chromosomal inversions. At the tryptophan oxygenase locus inside inversion 2Rb, variation was structured only by inversion orientation and not by taxonomic designation even between An. gambiae and An. arabiensis, providing the first molecular evidence that the 2Rb inversion was transferred between species by introgressive hybridization. By contrast, the rDNA showed fixed differences between species and a difference diagnostic for Mopti, consistent with effective, if not complete, reproductive isolation. The apparent disagreement between the data from this locus and multiple single-copy loci within An. gambiae may be explained by the much lower effective population size of rDNA, owing to concerted evolution, which confers increased sensitivity at much shorter divergence times. Taken together with the accompanying reports by della Torre et al. (2001), Favia et al. (2001) and Gentile et al. (2001), our data suggest that neutral molecular markers may not have the sensitivity required to detect isolation between these recently established taxa.

Effects of natural selection on patterns of DNA sequence variation at the transferrin, somatolactin, and p53 genes within and among chinook salmon (Oncorhynchus tshawytscha) populations.

This paper describes DNA sequence variation within and among four populations of chinook salmon (Oncorhynchus tshawytscha) at the transferrin, somatolactin and p53 genes. Patterns of variation among salmon species at the transferrin gene have been hypothesized to be shaped by positive natural selection for new alleles because the rate of nonsynonymous substitution is significantly greater than the rate of synonymous substitution. The twin goals of this study were to determine if the history of selection among salmon species at the transferrin gene is also reflected in patterns of intraspecific variation in chinook salmon, and to look for evidence of local adaptation at the transferrin gene by comparing patterns of nonsynonymous and synonymous variation among chinook salmon populations. The analyses presented here show that unlike patterns of variation between species, there is no evidence of greater differentiation among chinook salmon populations at nonsynonymous compared to synonymous sites. There is also no evidence of a reduction of within-species variation due to the hitchhiking effect at the transferrin gene, although in some populations nonsynonymous and synonymous derived mutations are both at higher frequencies than expected under a simple neutral model. Population size weighted selection coefficients (4Ns) that are consistent with both the inter and intraspecific data range from approximately 10 to approximately 235, and imply that between 1 and 40% of new nonsynonymous mutations at the transferrin gene have been beneficial.

Analysis of patterns of DNA sequence variation in flanking and coding regions of murine germ-line immunoglobulin heavy-chain variable genes: Evolutionary implications

Analysis of patterns of DNA sequence variation in flanking and coding regions of murine germ-line immunoglobulin heavy-chain variable genes: Evolutionary implications

Analysis of patterns of DNA sequence variation in flanking and coding regions of murine germ-line immunoglobulin heavy-chain variable genes: evolutionary implications.

We analyzed the DNA sequence structure of the 5' flanking and coding regions of 52 VH186.2-related germ-line genes isolated by PCR from C57BL/6J and BALB/c mice. The aligned coding regions display hypervariable and conserved regions corresponding to some of the complementarity-determining regions (CDRs) and framework regions (FRs) found in somatically mutated rearranged immunoglobulin variable genes. Most of the coding regions (88.5%) display open reading frames, strongly suggesting positive selection by antigen. Phylogenetic comparisons of putative transcribed regions versus 5' nontranscribed regions show that they have evolved very differently. Inspection of the 52 murine VH186.2-related DNA sequences (as well as other vertebrate germ-line V sequences reported in the literature) reveals clusters of insertion and deletion events bracketing the transcription/coding unit. These data strongly suggest hyperrecombination events targeting the putative transcription/coding sequence. Given that the DNA of unrearranged germ-line V elements cannot be the direct target for "natural-selection" antigen-binding forces (since V elements are only expressed somatically when rearranged in a mature lymphocyte), it is difficult to explain how these nonrandom sequence variations appear in the germ-line DNA. A number of molecular genetic processes are considered, including antigen-driven soma-to-germ-line gene feedback operative during vertebrate germ-line V gene evolution.