Human SNP variability and mutation rate are higher in regions of high recombination

Understanding the co-variation of nucleotide diversity and local recombination rates is important both for the mapping of disease-associated loci and in understanding the causes of sequence evolution. It is known that single nucleotide polymorphisms (SNPs) around protein coding genes show higher diversity in regions of high recombination. Here, we find that this correlation holds for SNPs across the entire human genome, the great majority of which are not near exons or control elements. Contrasting with results from coding regions, we provide evidence that the higher nucleotide diversity in regions of high recombination is most likely due, at least in part, to a higher mutation rate. One possible explanation for this is that recombination is mutagenic.     

Evidence for quantitative trait loci affecting twinning rate in North American Holstein cattle

Twinning in dairy cattle has been associated with many negative health and reproductive events that cause economic loss to the producer. Reports have suggested that twinning rates are increasing and that there may be a positive relationship between milk production and twinning frequency. Putative quantitative trait loci (QTL) for twinning and ovulation rate on bovine chromosomes 5, 7, 19 and 23 have been previously identified in other populations. The objective of this study was to detect and possibly confirm the existence and effects of these QTL in the North American Holstein population. Half-sib families of 20 North American Holstein sires with above average twinning rate predicted transmitting abilities (PTA) comprised the sample population under investigation. Twinning rate PTA values had been estimated from calving data. DNA extracted from semen samples was analysed using 45-61 microsatellite markers across the four chromosomes. Marker heterozygosity of the patriarchs averaged 62%. Evidence of twinning QTL was found in multiple families on chromosomes 5, 7 and 23 and in one family on chromosome 19. Four of the sires formed one three-generation family: one sire and three half-sib sons with sons of their own. This extended family was analysed with additional markers confirming a twinning QTL of significant size on chromosome 5.     

Evidence for recombination in Candida glabrata

Despite its clinical importance, little is known of the epidemiology and population structure of Candida glabrata. C. glabrata possesses a mating type system similar to that in Saccharomyces cerevisiae, however mating, meiosis and recombination have not been demonstrated. We performed multilocus sequence typing on a collection of 165 isolates to test for evidence of genetic recombination. A total of 3345 bp from six loci (FKS, LEU2, NMT1, TRP1, UGP1, and URA3) were sequenced for each isolate. The polymorphisms at these loci defined 34 sequence types. Significant evidence for a clonal population was revealed by the index of association and the number of phylogenetically compatible pairs of loci. However, 14 examples of phylogenetic incompatibility were also found. Thus we conclude that although C. glabrata has a predominantly clonal population structure, the multiple phylogenetic incompatibilities found strongly suggest that recombination occurred during the evolution of C. glabrata, and may infrequently still occur.     

Evidence for recombination in Mycobacterium tuberculosis

Due to its mostly isolated living environment, Mycobacterium tuberculosis is generally believed to be highly clonal, and thus recombination between different strains must be rare and is not critical for the survival of the species. To investigate the roles recombination could have possibly played in the evolution of M. tuberculosis, an analysis was conducted on previously determined genotypes of 36 synonymous single nucleotide polymorphisms (SNPs) in 3,320 M. tuberculosis isolates. The results confirmed the predominant clonal structure of the M. tuberculosis population. However, recombination between different strains was also suggested. To further resolve the issue, 175 intergenic SNPs and 234 synonymous SNPs were genotyped in 37 selected representative strains. A clear mosaic polymorphic pattern ahead of the MT0105 locus encoding a PPE (Pro-Pro-Glu) protein was obtained, which is most likely a result of recombination hot spot. Given that PPE proteins are thought to be critical in host-pathogen interactions, we hypothesize that recombination has been influential in the history of M. tuberculosis and possibly a major contributor to the diversity observed ahead of the MT0105 locus.     

Genomic correlates of recombination rate and its variability across eight recombination maps in the western honey bee (Apis mellifera L.)

Background

Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic recombination among multicellular animals with about five cross-over events per chromatid.

Results

Here, we present a comparative analysis of recombination rates across eight genetic linkage maps of the honey bee genome to investigate which genomic sequence features are correlated with recombination rate and with its variation across the eight data sets, ranging in average marker spacing ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best the variation in local recombination rate along chromosomes at the analyzed 100 kbp scale. In contrast, variation among the different maps was correlated to the abundance of microsatellites and several specific tri- and tetra-nucleotides.

Conclusions

The combined evidence from eight medium-scale recombination maps of the honey bee genome suggests that recombination rate variation in this highly recombining genome might be due to the DNA configuration instead of distinct sequence motifs. However, more fine-scale analyses are needed. The empirical basis of eight differing genetic maps allowed for robust conclusions about the correlates of the local recombination rates and enabled the study of the relation between DNA features and variability in local recombination rates, which is particularly relevant in the honey bee genome with its exceptionally high recombination rate.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1281-2) contains supplementary material, which is available to authorized users.     

Estimating digestion rate and the problem of individual variability, exemplified by a scyphozoan jellyfish

Ultrastructural changes in the intestinal epithelium of fed and starved specimens of Spadella cephaloptera are described. Animals were maintained in a circulating natural sea water system and fed with Artemia salina nauplii. After a period of acclimation, they were individually isolated, deprived of food for 24 h and submitted to controlled feeding experiments. The absorption develop in the intestinal absorptive cells (A-cells) 5 min after the ingestion of prey and consist in the formation of endocytotic vesicles and endosome-like vacuoles. During the following steps up to 10 h, a second type of digestive vacuole containing electron-dense material, and probably corresponding to a lysosome-like compartment, appears. Throughout this time, the vacuoles progressively arrange in columns, the youngest at the top and the oldest at the bottom of the A-cells. In addition, large lipid inclusions appear in the apical cytoplasm. The ultrastructural changes of the intestinal secretory cells (S-cells) is less marked, but the number of granules largely diminishes during the first 30 min after the ingestion of prey. In starved specimens, major changes in A-cells occur between the sixth and tenth day of starvation and consist in the increase of endosome-like vacuoles. Lysosome-like vacuoles containing dense material are not observed. At the same time, necrosis features are evident in S-cells. After 30 days of starvation, necrosis features are observed in the totality of the intestinal epithelium and the specimens die few days later.     

Human male recombination maps for individual chromosomes

Meiotic recombination is essential for the segregation of chromosomes and the formation of normal haploid gametes, yet we know very little about the meiotic process in humans. We present the first (to our knowledge) recombination maps for every autosome in the human male obtained by new immunofluorescence techniques followed by centromere-specific multicolor fluorescence in situ hybridization in human spermatocytes. The mean frequency of autosomal recombination foci was 49.8+/-4.3, corresponding to a genetic length of 2,490 cM. All autosomal bivalents had at least one recombination focus. In contrast, the XY bivalent had a recombination focus in 73% of nuclei, suggesting that a relatively large proportion of spermatocytes may be at risk for nondisjunction of the XY bivalent or elimination by meiotic arrest. There was a very strong correlation between mean length of the synaptonemal complex (SC) and the number of recombination foci per SC. Each bivalent presented a distinct distribution of recombination foci, but in general, foci were near the distal parts of the chromosome, with repression of foci near the centromere. The position of recombination foci demonstrated positive interference, but, in rare instances, foci were very close to one another.     

Management of athletic training taking into account individual heart rate variability characteristics

This article presents a new approach to planning and timely adjusting athletic trainings according to the data of the quick analysis of heart rate variability. It has been shown that individual types of regulation are different not only in the autonomic balance, but also in the degree of endurance of training and competition loads.     

Evidence for intra-cistronic recombination in Anopheles gambiae

Heterozygotes for the functionally allelic white and pink eye mutants in Anopheles gambiae yielded wild-type progeny at a rate of 3/25600. It is probable that this was due to intra-cistronic recombination.     

A method for the dynamic management of genetic variability in dairy cattle

According to the general approach developed in this paper, dynamic management of genetic variability in selected populations of dairy cattle is carried out for three simultaneous purposes: procreation of young bulls to be further progeny-tested, use of service bulls already selected and approval of recently progeny-tested bulls for use. At each step, the objective is to minimize the average pairwise relationship coefficient in the future population born from programmed matings and the existing population. As a common constraint, the average estimated breeding value of the new population, for a selection goal including many important traits, is set to a desired value. For the procreation of young bulls, breeding costs are additionally constrained. Optimization is fully analytical and directly considers matings. Corresponding algorithms are presented in detail. The efficiency of these procedures was tested on the current Norman population. Comparisons between optimized and real matings, clearly showed that optimization would have saved substantial genetic variability without reducing short-term genetic gains.     

PRP gene variability in the us cattle population

Abstract

The primary amino acid sequence of the prion protein (PrP) has previously been correlated with changes in the incubation period of subacute spongiform encephalopathies. We have analyzed the PrP gene from 65 different cattle representing 14 breeds by polymerase chain reaction and restriction enzyme analysis. Two distinct PrP alleles differing in the number of octapeptide repeats are present. The predominant genotype is homozygous for 6 octapeptide repeats. Few individuals (8) were found to be heterozygous for these repeats and only 1 animal was homozygous for the 5 octapeptide repeat allele.     

Evidence of recombination in the norovirus capsid gene

Noroviruses are single-stranded RNA viruses with high genomic variability. They have emerged in the last decade as a major cause of acute gastroenteritis. It remains so far unclear whether norovirus evolution is driven by sequence mutation and/or recombination. In this study, we have assessed the occurrence of recombination in the norovirus capsid gene. For this purpose, 69 complete capsid sequences of norovirus strains accessible in GenBank as well as 25 complete capsid sequences generated from norovirus-positive clinical samples were examined. Unreported recombination was detected in about 8% of norovirus strains belonging to genetic clusters I/1 (n = 1), II/1 (n = 1), II/3 (n = 1), II/4 (n = 3), and II/5 (n = 1). Recombination breakpoints were mainly located at the interface of the putative P1-1 and P2 domains of the capsid protein and/or within the P2 domain. The recombination region displayed features such as length, sequence composition (upstream and downstream GC- and AU-rich sequences, respectively), and predicted RNA secondary structure that are characteristic of homologous recombination activators. Our results suggest that recombination in the norovirus capsid gene may naturally occur, involving capsid domains presumably exposed to immunological pressure.     

Evidence for rare recombination at the gametophytic self-incompatibility locus

The gametophytic self-incompatibility locus has been thought to be a nonrecombining genomic region. Inferences have been made, however, about the functional importance of different parts of the S-locus, based on differences in the levels of variability along the gene, and this is valid only if recombination occurs. It is thus important to test whether recombination occurs within and near the S-locus. Several recent attempts to test this have reached conflicting conclusions. In this study, we examine a large data set on sequence variation at the S-locus in several species with gametophytic self-incompatibility systems, in the Solanaceae, Rosaceae and Scrophulariaceae. We use the longest sequences available to test for recombination based on linkage disequilibrium between polymorphic sites in the S-locus. The relationship between linkage disequilibrium and physical distance between the sites suggests rare intragenic exchange in the evolutionary history of four species of Solanaceae and two species of Rosaceae.     

Microsatellite variation and recombination rate in the human genome

Background (purifying) selection on deleterious mutations is expected to remove linked neutral mutations from a population, resulting in a positive correlation between recombination rate and levels of neutral genetic variation, even for markers with high mutation rates. We tested this prediction of the background selection model by comparing recombination rate and levels of microsatellite polymorphism in humans. Published data for 28 unrelated Europeans were used to estimate microsatellite polymorphism (number of alleles, heterozygosity, and variance in allele size) for loci throughout the genome. Recombination rates were estimated from comparisons of genetic and physical maps. First, we analyzed 61 loci from chromosome 22, using the complete sequence of this chromosome to provide exact physical locations. These 61 microsatellites showed no correlation between levels of variation and recombination rate. We then used radiation-hybrid and cytogenetic maps to calculate recombination rates throughout the genome. Recombination rates varied by more than one order of magnitude, and most chromosomes showed significant suppression of recombination near the centromere. Genome-wide analyses provided no evidence for a strong positive correlation between recombination rate and polymorphism, although analyses of loci with at least 20 repeats suggested a weak positive correlation. Comparisons of microsatellites in lowest-recombination and highest-recombination regions also revealed no difference in levels of polymorphism. Together, these results indicate that background selection is not a major determinant of microsatellite variation in humans.     

Species and recombination effects on DNA variability in the tomato genus

Population genetics theory predicts that strong selection for rare, beneficial mutations or against frequent, deleterious mutations reduces polymorphism at linked neutral (or weakly selected) sites. The reduction of genetic variation is expected to be more severe when recombination rates are lower. In outbreeding species, low recombination rates are usually confined to certain chromosomal regions, such as centromeres and telomeres. In contrast, in predominantly selfing species, the rarity of double heterozygotes leads to a reduced effective recombination rate in the whole genome. We investigated the effects of restricted recombination on DNA polymorphism in these two cases, analyzing five Lycopersicon species with contrasting mating systems: L. chilense, L. hirsutum, L. peruvianum, L. chmielewskii, and L. pimpinellifolium, of which only the first three species have self-incompatibility alleles. In each species, we determined DNA sequence variation of five single-copy genes located in chromosomal regions with either high or low recombination rate. We found that the mating system has a highly significant effect on the level of polymorphism, whereas recombination has only a weak influence. The effect of recombination on levels of polymorphism in Lycopersicon is much weaker than in other well-studied species, including Drosophila. To explain these observations, we discuss a number of hypotheses, invoking selection, recombination, and demographic factors associated with the mating system. We also provide evidence that L. peruvianum, showing a level of polymorphism (almost 3%) that is comparable to the level of divergence in the whole genus, is the ancestral species from which the other species of the genus Lycopersicon have originated relatively recently.     

Evidence for recombination of mitochondrial DNA in triploid crucian carp

In this study, we report the complete mitochondrial DNA (mtDNA) sequences of the allotetraploid and triploid crucian carp and compare the complete mtDNA sequences between the triploid crucian carp and its female parent Japanese crucian carp and between the triploid crucian carp and its male parent allotetraploid. Our results indicate that the complete mtDNA nucleotide identity (98%) between the triploid crucian carp and its male parent allotetraploid was higher than that (93%) between the triploid crucian carp and its female parent Japanese crucian carp. Moreover, the presence of a pattern of identity and difference at synonymous sites of mitochondrial genomes between the triploid crucian carp and its parents provides direct evidence that triploid crucian carp possessed the recombination mtDNA fragment (12,759 bp) derived from the paternal fish. These results suggest that mtDNA recombination was derived from the fusion of the maternal and paternal mtDNAs. Compared with the haploid egg with one set of genome from the Japanese crucian carp, the diploid sperm with two sets of genomes from the allotetraploid could more easily make its mtDNA fuse with the mtDNA of the haploid egg. In addition, the triple hybrid nature of the triploid crucian carp probably allowed its better mtDNA recombination. In summary, our results provide the first evidence of mtDNA combination in polyploid fish.     

Effect of reward level on individual variability in demand feeding activity and growth rate in Arctic charr and rainbow trout

Groups of Arctic charr and rainbow trout were fed by using demand feeders and their individual trigger actuations registered with a PIT-tag (Passive Integrated Transponder) system. Food was supplied at two reward levels, low and high, to five replicate groups of each species for 21 to 27 days. The reward level was defined as the amount of food obtained in response to a single trigger actuation. The effects of reward level on individual demand feeding activity and growth rale were assessed.
As a result of high demand feeding activity, the daily food rations for trout were in excess of their needs at both reward levels. This can be ascribed to the fact that they compensated a low reward level by increasing their bite activity. In contrast, demand feeding activity in charr did not differ significantly between reward levels. Instead, resulting food rations were limiting and excessive, at low and high reward levels, respectively. The variation in bite activity between individuals (measured as their proportional contribution to the total number of trigger actuations within a group) for charr was significantly higher in the low-reward treatment than in the high-reward level. For trout, the variation in bite activity did not differ significantly between treatments. Differences in response to reward level are suggested to be due to the fact that the social hierarchy is weaker in trout than in charr; i.e. the differences in bite activity between dominant and non-dominant individuals are smaller in trout. At both reward levels, the benefit of being dominant, measured in terms of growth rate was significant for charr but non-significant for trout.     

Evidence for an additional cattle DQB locus

 Studying the genetic polymorphism of the major histocompatibility complex class II genes in cattle, we identified a sequence (KUH1) which resembles those encoding class II β chains. The gene was shown to be transcribed in peripheral blood leukocytes. Sequence comparisons, Southern blot, and phylogenetic analyses indicate that (1) KUH1 represents a distinct DQB locus, which we propose to designate BoLA-DQB5, (2) DQB5 constitutes an ancient DQB locus which diverged from a common ancestor gene prior to the duplication resulting in DQB1 and DQB2, (3) DQB5 is associated with haplotypes which contain DQA5 and a duplicated DQ region. Received: 26 January 1999 / Revised: 20 April 1999