The (GA)(n) microsatellite has been known from previous studies to adopt unusual, ordered, cooperatively melting secondary structures in neutral aqueous solutions containing physiological concentrations of salts, at acid pH values or in aqueous ethanol solutions. To find more about the primary structure specificity of these structures, we performed parallel comparative studies of related tetranucleotide repeats (GAGC)(5), (GAGT)(5), and (GACA)(5). The general conclusion following from these comparative studies is that the primary structure specificity is fairly high, indicating that not only guanines but also adenines play a significant role in the stabilization of these unusual structures. (GAGC)(5) is a hairpin or a duplex depending on DNA concentration. Neither acid pH nor ionic strength or the presence of ethanol changed the secondary structure of (GAGC)(5) in a significant way. (GACA)(5) forms a weakly stable hairpin in neutral aqueous solutions but forms a duplex at acid pH where cytosine is protonated. (GAGT)(5) behaves most similar to (GAGA)(5). Salt induces its hairpin to duplex transition at neutral pH and an isomerization into another, probably parallel stranded, duplex takes place at acid pH. (GAGT)(5) is the only of the three present 20-mers that responds to ethanol like (GAGA)(5).
We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.
- MeSH
- Alleles MeSH
- Aromatase genetics MeSH
- White People genetics MeSH
- Genetic Markers MeSH
- Genotype MeSH
- Humans MeSH
- Microsatellite Repeats genetics MeSH
- Coronary Artery Disease ethnology genetics MeSH
- Polymorphism, Genetic MeSH
- Steroid 17-alpha-Hydroxylase MeSH
- Age of Onset MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- MeSH
- DNA analysis MeSH
- Hypertension MeSH
- Humans MeSH
- Blood Pressure Determination MeSH
- Microsatellite Repeats MeSH
- Norepinephrine blood MeSH
- Tyrosine 3-Monooxygenase genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comparative Study MeSH
Reliable representation of the B-DNA base-pair step twist is one of the crucial requirements for theoretical modeling of DNA supercoiling and other biologically relevant phenomena in B-DNA. It has long been suspected that the twist is inaccurately described by current empirical force fields. Unfortunately, comparison of simulation results with experiments is not straightforward because of the presence of BII backbone substates, whose populations may differ in experimental and simulation ensembles. In this work, we provide a comprehensive view of the effect of BII substates on the overall B-DNA helix twist and show how to reliably compare twist values from experiment and simulation in two scenarios. First, for longer DNA segments freely moving in solution, we show that sequence-averaged twists of different BI/BII ensembles can be compared directly because of approximate cancellation of the opposing BII effects. Second, for sequence-specific data, such as a particular base-pair step or tetranucleotide twist, can be compared only for a clearly defined BI/BII backbone conformation. For the purpose of force field testing, we designed a compact set of fourteen 22-base-pair B-DNA duplexes (Set 14) containing all 136 distinct tetranucleotide sequences and carried out a total of 84 μs of molecular dynamics simulations, primarily with the OL15 force field. Our results show that the ff99bsc0εζOL1χOL4, parmbsc1, and OL15 force fields model the B-DNA helical twist in good agreement with X-ray and minicircle ligation experiments. The comprehensive understanding obtained regarding the effect of BII substates on the base-pair step geometry should aid meaningful comparisons of various conformational ensembles in future research.
BACKGROUND: Tetranucleotide Short Tandem Repeats (STRs) for human identification and common use in forensic cases have recently been used to address the population genetics of the North-Eastern Mediterranean area. However, to gain confidence in the inferences made using STRs, this kind of analysis should be challenged with changes in three main aspects of the data, i.e. the sizes of the samples, their distance across space and the genetic background from which they are drawn. AIM: To test the resilience of the gradients previously detected in the North-Eastern Mediterranean to the enlargement of the surveyed area and population set, using revised data. SUBJECTS AND METHODS: STR genotype profiles were obtained from a publicly available database (PopAffilietor databank) and a dataset was assembled including >7000 subjects from the Arabian Peninsula to Scandinavia, genotyped at eight loci. Spatial principal component analysis (sPCA) was applied and the frequency maps of the nine alleles which contributed most strongly to sPC1 were examined in detail. RESULTS: By far the greatest part of diversity was summarised by a single spatial principal component (sPC1), oriented along a SouthEast-to-NorthWest axis. The alleles with the top 5% squared loadings were TH01(9.3), D19S433(14), TH01(6), D19S433(15.2), FGA(20), FGA(24), D3S1358(14), FGA(21) and D2S1338(19). These results confirm a clinal pattern over the whole range for at least four loci (TH01, D19S433, FGA, D3S1358). CONCLUSIONS: Four of the eight STR loci (or even alleles) considered here can reproducibly capture continental arrangements of diversity. This would, in principle, allow for the exploitation of forensic data to clarify important aspects in the formation of local gene pools.
- MeSH
- Gene Frequency * MeSH
- Genetic Variation * MeSH
- Genotype * MeSH
- Microsatellite Repeats * MeSH
- Genetics, Population MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Africa, Northern MeSH
- Middle East MeSH
- Mediterranean Region MeSH
The analysis of Y-chromosome variation has provided valuable clues about the paternal history of domestic animal populations. The main goal of the current work was to characterize Y-chromosome diversity in 31 goat populations from Central Eastern (Switzerland and Romania) and Southern Europe (Spain and Italy) as well as in reference populations from Africa and the Near East. Towards this end, we have genotyped seven single nucleotide polymorphisms (SNPs), mapping to the SRY, ZFY, AMELY and DDX3Y Y-linked loci, in 275 bucks from 31 populations. We have observed a low level of variability in the goat Y-chromosome, with just five haplotypes segregating in the whole set of populations. We have also found that Swiss bucks carry exclusively Y1 haplotypes (Y1A: 24%, Y1B1: 15%, Y1B2: 43% and Y1C: 18%), while in Italian and Spanish bucks Y2A is the most abundant haplotype (77%). Interestingly, in Carpathian goats from Romania the Y2A haplotype is also frequent (42%). The high Y-chromosome differentiation between Swiss and Italian/Spanish breeds might be due to the post-domestication spread of two different Near Eastern genetic stocks through the Danubian and Mediterranean corridors. Historical gene flow between Southern European and Northern African goats might have also contributed to generate such pattern of genetic differentiation.
- MeSH
- Y Chromosome genetics MeSH
- Genotype MeSH
- Haplotypes genetics MeSH
- Goats MeSH
- Microsatellite Repeats genetics MeSH
- Genetics, Population MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
- MeSH
- Alleles MeSH
- Haplotypes * MeSH
- Humans MeSH
- Chromosomes, Human, Y * MeSH
- Microsatellite Repeats * MeSH
- Forensic Genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Sexual parasites offer unique insights into the reproduction of unisexual and sexual populations. Because unisexuality is almost exclusively linked to the female sex, most studies addressed host-parasite dynamics in populations where sperm-dependent females dominate. Pelophylax water frogs from Central Europe include hybrids of both sexes, collectively named P. esculentus. They live syntopically with their parental species P. lessonae and/or P. ridibundus. Some hybrid lineages consist of all males providing a chance to understand the origin and perpetuation of a host-parasite (egg-dependent) system compared to sperm-dependent parthenogenesis. METHODS: We focused on P. ridibundus-P. esculentus populations where P. ridibundus of both sexes lives together with only diploid P. esculentus males. Based on 17 microsatellite markers and six allozyme loci, we analyzed (i) the variability of individual genomes, (ii) the reproductive mode(s) of all-male hybrids, and (iii) the genealogical relationships between the hybrid and parental genomes. RESULTS: Our microsatellite data revealed that P. esculentus males bear Mendelian-inherited ridibundus genomes while the lessonae genome represents a single clone. Our data indicate that this clone did not recently originate from adjacent P. lessonae populations, suggesting an older in situ or ex situ origin. CONCLUSIONS: Our results confirm that also males can perpetuate over many generations as the unisexual lineage and successfully compete with P. ridibundus males for eggs provided by P. ridibundus females. Natural persistence of such sex-specific hybrid populations allows to studying the similarities and differences between male and female reproductive parasitism in many biological settings.
- MeSH
- Genotype MeSH
- Hybridization, Genetic MeSH
- Microsatellite Repeats MeSH
- Reptilian Proteins genetics MeSH
- Ranidae genetics MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
