A plausible explanation for heart rates in mammals

We consider a simple model to give a plausible mechanical explanation of what are the actual resting heart rates of mammals optimized for. We study what is the optimal frequency for a viscoelastic fluid circulating in a pulsatile way through a network of tubes and conclude that the heart rate is not optimized to transport blood through the whole net. Rather, actual resting heart rates of mammals happen at frequencies that optimize flow in vessels of radii that correspond to large arteries, which bring oxygenated blood rapidly far away from the heart, towards head and limbs. Our results for the optimal frequencies, obtained using observed radii of femoral arteries in mammals, agree best with the heart rates observed. We find a theoretical allometric relation between optimal flow frequency and radius: ν∼R⁻¹. This one, agrees with the exponent obtained when plotting observed heart rates versus radii of both, femoral arteries and carotids in mammals of different sizes, from mice to horses.     

DNA variability and recombination rates at X-linked loci in humans.

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 (pi) in humans, (ii) investigate whether there is variation in pi 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 pi 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, pi 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.     

Negative correlation between compositional symmetries and local recombination rates

Although still not much understood, the universal reverse complement symmetry in genomes may contain much information about the genome. In this article, under the hypothesis that recombination rate variations may be related to the high order DNA structure, we studied the association between local recombination rates and local symmetry levels in mouse, rat and human. We found significant negative correlations between recombination rates and reverse complement compositional symmetries in these three organisms. This negative correlation pattern also held at individual chromosome levels when data only from each individual chromosome was analyzed.     

Properties of a neutral allele model with intragenic recombination

An infinite-site neutral allele model with crossing-over possible at any of an infinite number of sites is studied. A formula for the variance of the number of segregating sites in a sample of gametes is obtained. An approximate expression for the expected homozygosity is also derived. Simulation results are presented to indicate the accuracy of the approximations. The results concerning the number of segregating sites and the expected homozygosity indicate that a two-locus model and the infinite-site model behave similarly for 4Nu less than or equal to 2 and r less than or equal to 5u, where N is the population size, u is the neutral mutation rate, and r is the recombination rate. Simulations of a two-locus model and a four-locus model were also carried out to determine the effect of intragenic recombination on the homozygosity test of Watterson (Genetics 85, 789-814; 88, 405-417) and on the number of unique alleles in a sample. The results indicate that for 4Nu less than or equal to 2 and r less than or equal to 10u, the effect of recombination is quite small.     

A transient assay in plant cells reveals a positive correlation between extrachromosomal recombination rates and length of homologous overlap.

An assay to monitor homologous recombination in plant cells has been established by cotransfecting Nicotiana plumbaginifolia protoplasts with different topological forms of plasmids of various deletion mutants of a non-selectable marker gene, the beta-glucuronidase (GUS) gene. Transient GUS enzyme activities were measured by a sensitive assay. In the nuclear DNA of the cotransfected protoplasts the recombined complete GUS gene could be detected by a specially modified PCR analysis. In comparison to the standard assay, which monitors homologous recombination by integration of a selectable marker, the described assay avoids position effects of gene expression, is fast, easy to handle and large numbers of samples can be processed simultaneously. We were able to demonstrate a positive correlation between the length of overlapping homology (up to 1200 base pairs) of the transfected supercoiled circular or linearized plasmids and the respective GUS activities. We found a significant drop in the recombination rates when the overlap of both substrates was reduced to 456 basepairs or less. The requirement for such a long stretch of homology for efficient recombination might ensure the stability of the rather repetitive plant genome.     

Zygotic algebra for two linked loci with sexually different recombination rates

This is a study of the properties of a zygotic algebra of two linked autosomal loci with different recombination rates in males and females, without selection or mutation and with random mating. The above-mentioned zygotic algebra contains a genetic subalgebra. A canonical basis of this subalgebra is constructed and the train roots are calculated.     

Age-dependent recombination rates in human pedigrees

In humans, chromosome-number abnormalities have been associated with altered recombination and increased maternal age. Therefore, age-related effects on recombination are of major importance, especially in relation to the mechanisms involved in human trisomies. Here, we examine the relationship between maternal age and recombination rate in humans. We localized crossovers at high resolution by using over 600,000 markers genotyped in a panel of 69 French-Canadian pedigrees, revealing recombination events in 195 maternal meioses. Overall, we observed the general patterns of variation in fine-scale recombination rates previously reported in humans. However, we make the first observation of a significant decrease in recombination rates with advancing maternal age in humans, likely driven by chromosome-specific effects. The effect appears to be localized in the middle section of chromosomal arms and near subtelomeric regions. We postulate that, for some chromosomes, protection against non-disjunction provided by recombination becomes less efficient with advancing maternal age, which can be partly responsible for the higher rates of aneuploidy in older women. We propose a model that reconciles our findings with reported associations between maternal age and recombination in cases of trisomies.     

A note on the correlation between heterozygosity and recombination rate

Mechanisms responsible for the correlation between heterozygosity and recombination rate have been thought to be background selection and selective sweep. In addition to these two, diversity enhancing selection and/or gene conversion is suggested to be contributing to the correlation, by surveying some examples of highly polymorphic loci that tend to locate in high-recombination regions.     

A correlation of phylogenetic diversity in the Proteobacteria with the influences of ecological forces.

The Proteobacteria are physiologically and morphologically diverse, although they form a coherent set of four main lineages on phylogenetic analysis of ribosomal RNA. A rational and consistent taxonomic arrangement bringing today's phenotypic and phylogenetic conclusions about them into register is not yet possible. It is also difficult to understand the selective forces involved in their evolution that fostered such diversity. This latter problem is addressed in this essay and is based on the assumption that bacterial evolution could only have occurred in ecological consortia whose products of metabolism modified the environment, provided nutrition, and have a basis for selection of new capabilities.     

Deletion polymorphism in wheat chromosome regions with contrasting recombination rates

Polymorphism for deletions was investigated in 1027 lines of tetraploid and hexaploid wheat and 420 lines of wheat diploid ancestors. A total of 26 deletions originating during the evolution of polyploid wheat were discovered among 155 investigated loci. Wheat chromosomes were divided into a proximal, low-recombination interval containing 69 loci and a distal, high-recombination interval containing 86 loci. A total of 23 deletions involved loci in the distal, high-recombination interval and only 3 involved loci in the proximal, low-recombination interval. The rates of DNA loss differed by several orders of magnitude in the two intervals. The rate of diploidization of polyploid wheat by deletions was estimated and was shown to have proceeded faster in the distal, high-recombination interval than in the proximal, low-recombination interval.     

Species diversity in local neutral communities

We extend the neutral theory of macroecology by deriving biodiversity models (relative species abundance and species-area relationships) in a local community-metacommunity system in which the local community is embedded within the metacommunity. We first demonstrate that the local species diversity patterns converge to that of the metacommunity as the size (scale) of the embedded local community increases. This result shows that in continuous landscapes no sharp boundaries dividing the communities at the two scales exist; they are an artificial distinction made by the current spatially implicit neutral theory. Second, we remove the artificial restriction that speciation cannot occur in a local community, even if the effects of local speciation are small. Third, we introduce stochasticity into the immigration rate, previously treated as constant, and demonstrate that local species diversity is a function not only of the mean but also of the variance in immigration rate. High variance in immigration rates reduces species diversity in local communities. Finally, we show that a simple relationship exists between the fundamental diversity parameter of neutral theory and Simpson's index for local communities. Derivation of this relationship extends recent work on diversity indices and provides a means of evaluating the effect of immigration on estimates of the fundamental diversity parameter derived from relative species abundance data on local communities.     

A whole genome scan for differences in recombination rates among three Bos taurus breeds

Twenty paternal half-sib families of a granddaughter design were genotyped for 265 genetic markers, most of them microsatellites. These were 16 Holstein families, 3 Simmental families, and 1 Brown Swiss family. The number of sires per breed was 872, 170, and 32, respectively. Two-point recombination rates were estimated both jointly for all breeds and each single breed separately. Of 1168 marker intervals, 865 provided estimates for at least two breeds. Differences between breeds were tested by likelihood ratio tests. Four marker intervals, representing three genomic regions on BTA19, BTA24, and BTA27, show a significant impact of the breed at a false discovery rate of 0.23 and indicate a genetic component of observed heterogeneity of recombination. The variability of recombination rates between cattle breeds might not be a common feature of the whole genome, but rather might be restricted to certain chromosomal segments. Thus, attention should be paid to heterogeneities when pooling data of such regions from different breeds. Received: 14 March 2001 / Accepted: 8 May 2001     

Intermolecular plasmid recombination in fibroblasts from humans with DNA damage-processing defects

We have evaluated the ability of immortalized human fibroblasts to recombine transfected plasmid DNA. A number of cell lines from normal individuals and from patients with DNA damage-processing defects were examined. Two plasmid recombination substrates were derived from pSV2neo and contained nonoverlapping deletions in the aminoglycoside phosphotransferase II gene. Intermolecular recombination was assessed by two methods after cotransfection. In a short-term, extrachromosomal recombination assay, low molecular weight DNA was extracted from the human cells 48 h after transfection, and recombinant plasmids were detected by transformation into appropriate indicator bacteria. In a long-term stable recombination assay the fibroblasts were cotransfected and G418-resistant colonies allowed to form. By the former assay all but two cultures were recombination-proficient, whereas all were recombination-proficient by the latter assay. The efficiency of transfection of human cells with plasmids appears to be a major variable affecting recombination. Recombination can be stimulated by uv irradiation of plasmid DNA prior to transfection. Cells from patients with Fanconi anemia, ataxia telangiectasia, and xeroderma pigmentosum complementation groups A, C, D, E, and G are not defective at intermolecular plasmid recombination.     

MareyMap: an R-based tool with graphical interface for estimating recombination rates

Comparing genetic and physical maps (the so-called Marey map approach) is still the most widely used approach to estimate genome-wide recombination rates. Remarkably, there is no available bioinformatics tool specifically devoted to Marey map approach. Here, we developed such a tool called MareyMap based on GNU R and Tcl/Tk. MareyMap offers a user-friendly graphical interface and includes useful features, such as data cleaning process, sophisticated interpolation methods to estimate local rates, possibility of complex queries, various range of import-export files. Moreover, MareyMap comes with ready-to-use maps for human, Drosophila, Caenorhabditis elegans and Arabidopsis. MareyMap has been made so that it can be easily upgraded with new data and interpolation methods. Availability: http://pbil.univ-lyon1.fr/software/mareymap/.     

Non-reciprocal recombination as an explanation of aberrant segregation in Chlamydomonas reinhardi

Summary In crosses of a p-aminobencoic acid requiring mutant of Chlamydomonas reinhard with the wildtype we observed besides the expected 4:4 segregation a surprisingly high frequency of aberrant segregation, all of which preferentially led to the wildtype. The only possible explanation of this finding is a non-reciprocal recombination, as mutations, trisomy and the loss of a tetrad cell with following additional division of a sister cell can be excluded. The molecular mechanism of non-reciprocal recombinations is still unknown. Nevertheless our findings are best understood, if we accept the hybrid-DNA model of Holliday, especially because this model is not only able to explain the 5:3 and 6:2 tetrads, but also the 7:1 and 8:0 segregations which occur at a much lower rate.The frequency of non-reciprocal recombinations could be reduced by irradiating zygotes at the very beginning of the germination period. If the X-rays were applicated 61/2 hours after induction of the germination, no clear aberrant segregation could be found.The reduction of the frequency of non-reciprocal recombinations by X-rays leads to the conclusion, that the mechanism of mutation and conversion are not identical. On the other hand we known many mutagenic substances which also cause non-reciprocal recombination. Thus it can be supposed that both the mechanisms have some steps in common.     

Variation in recombination rates across Vitis species

Recombination rate data are presented for three populations of grape based on framework genetic linkage maps developed with simple-sequence repeat markers. These linkage maps were constructed from different Vitis species and represent three genetic backgrounds. The first population is pure Vitis vinifera, derived from a cross of the European cultivars Riesling and Cabernet Sauvignon. The second is an interspecific cross between two commercially used rootstock cultivars of different North American Vitis species parentage, Ramsey (Vitis champinii) and Riparia Gloire (Vitis riparia). The third population, D8909-15 (Vitis rupestris × (Vitis arizonica/Vitis girdiana form)) × F8909-17 (V. rupestris × (V. arizonica/Vitis candicans form)), is an F1 from two half-sibs. Genome-wide and chromosome-wide recombination rates varied across the three populations and among the six Vitis parents. Global recombination rates in the parents of the third F1 population, with a complex Vitis background, were significantly reduced. In the first and third populations, the recombination rate was significantly greater in the male parent. Specific genome locations with frequent heterogeneity in recombination were identified, suggesting that recombination rates are not equal across the Vitis genome. The identification of regions with suppressed or high recombination will aid grape breeders and geneticists who rely on recombination events to introgress disease resistance genes from the genomes of wild Vitis species, develop fine-scale genetic maps, and clone disease resistance genes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Similarity in recombination rate estimates highly correlates with genetic differentiation in humans

Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans. We calculated the recombination rates between adjacent pairs of 636,933 common single-nucleotide polymorphism loci in 28 worldwide human populations and analyzed them in relation to genetic distances between populations. We found a strong and highly significant correlation between similarity in the recombination rates corrected for effective population size and genetic differentiation between populations. This correlation is observed at the genome-wide level, but also for each chromosome and when genetic distances and recombination similarities are calculated independently from different parts of the genome. Moreover, and more relevant, this relationship is robustly maintained when considering presence/absence of recombination hotspots. Simulations show that this correlation cannot be explained by biases in the inference of recombination rates caused by haplotype sharing among similar populations. This result indicates a rapid pace of evolution of recombination, within the time span of differentiation of modern humans.     

A comparison of two-point, three-point and deletion mapping in the C cistron of rhizobiophage 16-3, with an explanation for the recombination pattern

A general tendency for additivity prevailed in recombination frequencies for two-point fine-structure mapping of 14 mutants in the C cistron of Rhizobium meliloti phage 16–3, with little evidence of any marker effect. Intracistronic three-point mapping indicated that double crossovers are rare. Deletion mapping indicated that the two- and three-point mapping data gave the correct order of the mutations. A high frequency (5 to 8%) of c/c⁺ heterozygotic phage progenies was observed in standard crosses. This pattern implies formation of a relatively long region of heterozygosity. Together with the results of the three-point tests, it suggests certain properties of the branch migration and resolution steps envisioned in current mechanisms of recombination.