Average Pairwise Distance Research Articles

Diversity analysis of provitamin A maize inbred lines using single nucleotide polymorphism markers

ABSTRACTThe success of a breeding programme can be determined by the level of genetic diversity that exists among breeding materials. This study was carried out to (i) determine the level of genetic diversity that exist among the collection of tropical provitamin A maize inbred lines and (ii) evaluate the genetic structure and divergence of provitamin A maize inbred lines. Forty-six advanced provitamin A inbred lines obtained from the International Maize and Wheat Improvement Centre (CIMMYT) and International Institute of Tropical Agriculture (IITA) were genotyped using 3047 single nucleotide polymorphism (SNP) markers. Genotyping was done following an Illumina Infinium HD Assay Ultra protocol. Eight six percent of the SNPs were polymorphic with the mean polymorphic information content of 0.36. Cluster analysis displayed two distinct clusters. The average pairwise genetic distance among the inbred lines was 0.60. The average gene diversity was 0.359. Variation was partitioned into among individuals (78%), among populations (12%) and within individuals (10%). Overall results suggest the inbred lines are genetically diverse. The key implication of this study is that selection should be done from genetically diverse inbred lines in order to exploit heterosis when developing hybrids.

Evaluation of genetic diversity, agronomic traits, and anthracnose resistance in the NPGS Sudan Sorghum Core collection

BackgroundThe United States Department of Agriculture (USDA) National Plant Germplasm System (NPGS) sorghum core collection contains 3011 accessions randomly selected from 77 countries. Genomic and phenotypic characterization of this core collection is necessary to encourage and facilitate its utilization in breeding programs and to improve conservation efforts. In this study, we examined the genome sequences of 318 accessions belonging to the NPGS Sudan sorghum core set, and characterized their agronomic traits and anthracnose resistance response.ResultsWe identified 183,144 single nucleotide polymorphisms (SNPs) located within or in proximity of 25,124 annotated genes using the genotyping-by-sequencing (GBS) approach. The core collection was genetically highly diverse, with an average pairwise genetic distance of 0.76 among accessions. Population structure and cluster analysis revealed five ancestral populations within the Sudan core set, with moderate to high level of genetic differentiation. In total, 171 accessions (54%) were assigned to one of these populations, which covered 96% of the total genomic variation. Genome scan based on Tajima’s D values revealed two populations under balancing selection. Phenotypic analysis showed differences in agronomic traits among the populations, suggesting that these populations belong to different ecogeographical regions. A total of 55 accessions were resistant to anthracnose; these accessions could represent multiple resistance sources. Genome-wide association study based on fixed and random model Circulating Probability (farmCPU) identified genomic regions associated with plant height, flowering time, panicle length and diameter, and anthracnose resistance response. Integrated analysis of the Sudan core set and sorghum association panel indicated that a large portion of the genetic variation in the Sudan core set might be present in breeding programs but remains unexploited within some clusters of accessions.ConclusionsThe NPGS Sudan core collection comprises genetically and phenotypically diverse germplasm with multiple anthracnose resistance sources. Population genomic analysis could be used to improve screening efforts and identify the most valuable germplasm for breeding programs. The new GBS data set generated in this study represents a novel genomic resource for plant breeders interested in mining the genetic diversity of the NPGS sorghum collection.

1891. Invasive Group A Streptococcus Infections Among Residents of Multiple Nursing Homes—Denver, Colorado, 2017–2018

BackgroundOlder adults residing in nursing homes (NH) are at increased risk for invasive group A Streptococcus (GAS) infections due to advanced age, presence of wounds, and comorbidities; approximately one-third of infected patients die. Beginning in 2015, increasing numbers of GAS infections in NH residents and several NH clusters were reported from the Denver metropolitan area. Colorado Department of Public Health and Environment (CDPHE) and CDC investigated to characterize cases and assess if outbreaks resulted from interfacility transmission.MethodsWe reviewed data from Active Bacterial Core surveillance (ABCs) in the 5-county Denver area from January 2017 to June 2018. We defined a case as isolation of GAS from a normally sterile site in an NH resident. GAS isolates underwent whole-genome sequencing (WGS) at CDC’s Streptococcus Laboratory to determine emm types for genotyping. Among isolates with the same emm type, pairwise single-nucleotide polymorphism (SNP) distances were calculated using Nucmer software. In October 2018, a CDPHE-CDC team assessed infection control at NHs with cases of the most common emm type.ResultsOver 18 months, among >100 NHs in the Denver area, ≥1 GAS case was identified in 29 NHs, with 6 having ≥3 cases. During this period, 68 cases in NH residents were identified. WGS identified 17 emm types among isolates from these cases; most common was emm11.10 (34%, n = 22), a rare subtype in ABCs. All emm11.10 isolates had nearly identical genomes (average pairwise SNP distance: 3.2), and were isolated from 10 NHs, with 2 NHs having ≥ 4 cases. Multiple infection control lapses were noted during site visits to 8 NHs.ConclusionMultiple outbreaks due to GAS were noted in 5-county Denver area NHs in 2017–2018. WGS of surveillance isolates identified a rarely seen emm subtype 11.10 from multiple facilities with temporal and genomic clustering suggesting interfacility GAS transmission. Disclosures All Authors: No reported Disclosures.

Genetic analysis of NS5B gene from bovine viral diarrhea virus-infected cattle in Central and East Java, Indonesia.

Background and Aim:A previous study divided Indonesian bovine viral diarrhea virus (BVDV)-1 into subgenotypes BVDV-1a to BVDV-1d based on the partial NS5B gene using strain Bega as reference for BVDV-1a. In fact, it is clustered into BVDV-1c with strain Bega-like Australia. BVDV genotyping has been done on isolates from Jakarta, West and Central Java, but East Java isolates have not been genotyped. This study aimed to analyze genetic variability and amino acid residues in the nucleotide-binding pocket of the NS5B gene from infected cattle.Materials and Methods:Samples were obtained from the Sera Bank originating from active and passive surveillance of cattle that had been tested for BVDV antigen from 2013 to 2017. Detection of the p80 antibody and BVDV genotyping was carried out using ELISA and nested-multiplex-polymerase chain reaction (PCR), respectively. We defined 15 nested PCR products for partial sequencing of NS5B. Those field samples were selected from each location and year using proportional calculation as a representative sample. Homological and phylogenetic analyses of the partial NS5B gene were performed using BLAST and MEGA version 6.Results:Based on the phylogenetic tree analysis using 360 nucleotides as the partial NS5B gene, Indonesian BVDV-1 isolates from Central and East Java were subdivided to BVDV-1a (n=9), BVDV-1b (n=1), and BVDV-1c (n=5). In the present study, the homology of BVDV subgenotype -1a, -1b, and -1c was compared to the BVDV GenBank data and found 90-93%, 93%, and 92-95% respectively with the average pairwise distance of 0.207. A point mutation was shown at R283K of all BVDV isolates based on the sequence of three amino acid residues R283, R285, and I287 in the nucleotide-binding pocket as a part of the encoded RNA-dependent RNA polymerase.Conclusion:This study revealed the genetic variability of BVDV infecting cattle in Central Java and East Java, Indonesia, the subtypes BVDV-1a, BVDV-1b, BVDV-1c, and a point mutation at the R283K residue.

Variability in the Global Proso Millet (Panicum miliaceum L.) Germplasm Collection Conserved at the ICRISAT Genebank

Proso millet (Panicum miliaceum L.), also known as common millet or broomcorn millet, is an important ancient crop mostly grown for food, feed, and fodder purposes largely in China, Russia, India, and the USA. It is an under-researched and under-utilized crop. Over 29,000 germplasm accessions have been conserved in genebanks globally. Five races (miliaceum, patentissimum, contractum, compactum, ovatum) have been recognized in proso millet based on panicle morphology and shape. The genebank at the International Crops Research Institute for the Semi-Arid Tropics conserves 849 accessions of proso millet originating from 30 countries and represents all five races. Characterization of these germplasm accessions revealed large variability for morpho-agronomic traits, including for days to 50% flowering (26 to 50 days), plant height (20 to 133 cm), and inflorescence length (22 to 400 mm). On average, the race miliaceum was tall (62 cm) with long panicles (209 mm) and ovatum had short plants (46 cm) with small panicles (108 mm). The average Gower’s distance based on 18 morpho-agronomic traits on 841 accessions was 0.261. The race miliaceum had the highest among accessions within race average pairwise distance (0.254), while the distance was the lowest in ovatum (0.192). The races miliaceum and ovatum showed the highest divergence with each other (0.275), while the lowest divergence was observed between compactum and ovatum (0.229). Trait-specific sources were identified for early maturity, tall plants, long inflorescences, and greater seed size. The information on variability and trait-specific sources identified could potentially support proso millet improvement.

Review of Brazilian jawfishes of the genus Opistognathus with descriptions of two new species (Teleostei, Opistognathidae)

A new species of jawfish, Opistognathusthionyisp. n., is described from the Vitória-Trindade Chain and Fernando de Noronha Archipelago off Brazil, a disjunct distribution of ca. 1,800 km. Opistognathusthionyi and its allopatric Caribbean sister-species, Opistognathusmaxillosus, both have a wide, fan-like upper margin of the subopercular flap and mostly over-lapping meristic data. The new species differs from O.maxillosus in having the darkest spot on the spinous dorsal fin, when present, between spines 2–5, versus always present between spines 6–9, the buccal area surrounding the esophageal opening pale versus very dark and fewer oblique scale rows in longitudinal series (45–52 vs. 69–85). A second new species, Opistognathusvicinussp. n., known from Brazil’s mainland, has completely over-lapping meristic values with its allopatric Caribbean sister-species O.whitehursti, but differs in lacking vomerine teeth and a supramaxilla and retaining the juvenile color pattern of the latter species in adults. Diagnoses, photographs, an identification key, and distributional maps are given for all Brazilian species of Opistognathus.Molecular phylogenetic analysis of partial cytochrome c oxidase subunit-I sequences indicates that specimens of the two allopatric pairs, O.thionyi – O.maxillosus and O.vicinus – O.whitehursti, form reciprocally monophyletic groups that differ from each other on average by 9 to 11%, with less than 1% average pair-wise genetic distance within-species. Similar patterns of phylogenetic structure were observed between reciprocally monophyletic (predominately allopatric) groups within nominal species of Opistognathusaurifrons, suggesting the possibility of at least two additional undescribed species from the Brazilian Province.

Blooming Trees: Substructures and Surrounding Groups of Galaxy Clusters

Abstract We develop the Blooming Tree Algorithm, a new technique that uses spectroscopic redshift data alone to identify the substructures and the surrounding groups of galaxy clusters, along with their member galaxies. Based on the estimated binding energy of galaxy pairs, the algorithm builds a binary tree that hierarchically arranges all of the galaxies in the field of view. The algorithm searches for buds, corresponding to gravitational potential minima on the binary tree branches; for each bud, the algorithm combines the number of galaxies, their velocity dispersion, and their average pairwise distance into a parameter that discriminates between the buds that do not correspond to any substructure or group, and thus eventually die, and the buds that correspond to substructures and groups, and thus bloom into the identified structures. We test our new algorithm with a sample of 300 mock redshift surveys of clusters in different dynamical states; the clusters are extracted from a large cosmological N-body simulation of a ΛCDM model. We limit our analysis to substructures and surrounding groups identified in the simulation with mass larger than 1013 h −1 M ⊙. With mock redshift surveys with 200 galaxies within 6 h −1 Mpc from the cluster center, the technique recovers 80% of the real substructures and 60% of the surrounding groups; in 57% of the identified structures, at least 60% of the member galaxies of the substructures and groups belong to the same real structure. These results improve by roughly a factor of two the performance of the best substructure identification algorithm currently available, the σ plateau algorithm, and suggest that our Blooming Tree Algorithm can be an invaluable tool for detecting substructures of galaxy clusters and investigating their complex dynamics.

The mitochondrial genome of the Kentish Plover Charadrius alexandrinus (Charadriiformes: Charadriidae) and phylogenetic analysis of Charadrii.

The suborder Charadrii (Aves: Charadriiformes), one of the most species-rich radiations within shorebirds, which contains good source for studies of ecology, behaviour and evolution. The resources of mitogenome have rapidly accumulated in recent years due to the advanced genomic sequencing, while suborder Charadrii's mitogenome has not been well studied. The primary objective of this study was to determine the complete mitogenome sequence of Charadrius alexandrinus, and investigated the evolutionary relationship within Charadrii. The mitogenome of C. alexandrinus were generated by amplification of overlapping Polymerase Chain Reaction (PCR) fragments. In this study, we determined the complete mitogenome sequence of the Kentish Plover Charadrius alexandrinus, and comparative analysed 11 species to illustrate mitogenomes structure and investigated their evolutionary relationship within Charadrii. The Charadrii mitogenomes displayed moderate size variation, the mean size was 16,944bp (SD = 182, n = 11), and most of the size variation due to mutations in the control region (CR). Nucleotide composition was consistently biased towards AT rich, and the A+T content also varies for each protein-coding genes. The variation in ATP8 and COIII was the highest and lowest respectively. The GC skew was always negative, with the ATP8 had higher value than other regions. The average uncorrected pairwise distances revealed heterogeneity of evolutionary rate for each gene, the COIII, COI and COII have slow evolutionary rate, whereas the gene of ATP8 has the relative fast rate. The highest value of Ks and Ka were ND1 and ATP8, and the ratios of Ka/Ks are lower than 0.27, indicating that they were under purifying selection. Phylogenomic analysis based on the complete mitochondrial genomes strongly supported the monophyly of the suborder Charadrii. This study improves our understanding of mitogenome structure and evolution, and providing further insights into phylogeny and taxonomy in Charadrii. In future, sequencing more mitogenomes from various taxonomic levels will significantly improve our understanding of phylogenetic relationships within Charadrii.

Variations in mitochondrial cytochrome b region among Ethiopian indigenous cattle populations assert Bos taurus maternal origin and historical dynamics.

ObjectiveThis study was carried out to assess the haplotype diversity and population dynamics in cattle populations of Ethiopia.MethodsWe sequenced the complete mitochondrial cytochrome b gene of 76 animals from five indigenous and one Holstein Friesian×Barka cross bred cattle populations.ResultsIn the sequence analysis, 18 haplotypes were generated from 18 segregating sites and the average haplotype and nucleotide diversities were 0.7540±0.043 and 0.0010±0.000, respectively. The population differentiation analysis shows a weak population structure (4.55%) among the populations studied. Majority of the variation (95.45%) is observed by within populations. The overall average pair-wise distance (F ST) was 0.049539 with the highest (F ST = 0.1245) and the lowest (F ST = 0.011) F ST distances observed between Boran and Abigar, and Sheko and Abigar from the indigenous cattle, respectively. The phylogenetic network analysis revealed that all the haplotypes detected clustered together with the Bos taurus cattle and converged to a haplogroup. No haplotype in Ethiopian cattle was observed clustered with the reference Bos indicus group. The mismatch distribution analysis indicates a single population expansion event among the cattle populations.ConclusionOverall, high haplotype variability was observed among Ethiopian cattle populations and they share a common ancestor with Bos taurus.

Dynamics of social behaviour at parturition in a gregarious ungulate

Group living is the behavioural response that results when individuals assess the costs vs benefits of sociality, and these trade-offs vary across an animal’s life. Here we quantitatively assess how periparturient condition (mother/non-mother) and births affect the dynamics of social interactions of a gregarious ungulate, and how such can help to explain evolutionary hypotheses of the mother-offspring bond. To achieve this we used data of the individual movement of a group of Scottish blackface sheep (Ovis aries) marked with GPS collars and properties of mathematical graphs (networks). Euclidean pair-wise distance between sheep were threshold at different percentiles to determine network links, and these thresholds have a profound effect on the connectivity of the resulting network. Births increased the average pair-wise distance between mothers, and between mothers and non-mothers, with less effect on the distance between non-mothers. Mothers occupied peripheral positions within the flock, more evident following births. Associations between individuals (i.e. network community change) were highly dynamic, though mothers were less likely to change community than non-mothers, especially after births. Births hampered individual communication within the flock (assessed via network closeness centrality), especially in mothers. Overall leadership (lead positioning relative to flock movement) was not associated to reproductive condition, and individual leadership rank was not affected by births. A ten minute GPS acquisition time was adequate to capture complex social dynamics in sheep movement. The results on mother’s isolation behaviour support the hypotheses of selection for maternal imprint facilitation, reducing risks to nursing alien offspring, and group/multilevel selection on group formation.

Lower pre-ART intra-participant HIV-1 pol diversity may not be associated with virologic failure in adults.

BackgroundIdentifying pre-ART factors associated with the emergence of HIV-1 drug resistance is critical for optimizing strategies to prevent virologic failure. A previous study reported that lower pre-ART HIV-1 pol diversity was associated with higher risk of virologic failure in HIV-1-infected children. To investigate this association in adults, we measured HIV-1 diversity with deep sequencing in pre-ART samples from adults with well-characterized virologic outcomes in a study (A5142) of initial ART conducted by the AIDS Clinical Trials Group (ACTG).MethodsWe identified 22 cases in ACTG A5142 who experienced virologic failure with drug resistance mutations in RT and 44 matched controls who did not experience virologic failure. cDNA was synthesized from plasma HIV-1 RNA. Each cDNA molecule was tagged with a unique primer ID and RT codons 41–103 were amplified and deep sequenced. Sequences with the same tag were aligned and a consensus was generated to reduce PCR and sequencing errors. Diversity was calculated by measuring average pairwise distance (APD) of the consensus sequences. An exact conditional logistic regression model with percent APD as the risk factor estimated the odds ratio for VF and the corresponding 95% confidence interval.ResultsConsensus single-genome sequences and diversity estimates of pol were obtained for pre-ART samples from 21 cases and 42 controls. The median (IQR) pre-ART percent APD was 0.71 (0.31–1.13) in cases and 0.58 (0.32–0.94) in controls. A possible trend was found for higher diversity being associated with greater risk of virologic failure in adults (OR = 2.2 per one percent APD increase, 95% CI = [0.8, 7.2]; p = 0.15).ConclusionsThis study in adults suggests there is a positive association between higher pre-ART pol diversity and the risk of virologic failure in adults rather than an inverse relationship reported in children.

Estimating time of HIV-1 infection from next-generation sequence diversity.

Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection. The results were validated on a second dataset from 31 patients. Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing that diversity in NGS data yields superior estimates to the number of ambiguous sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of deep NGS was utilized with continuous diversity measures such as average pairwise distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene were used. For these data, TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 years at 6 years. Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection many years after the infection, in contrast to most alternative biomarkers. We provide the regression coefficients as well as web tool for TI estimation.

Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers

BackgroundOngoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir’s reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51–400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80–2000 copies/mL) viremia (VC, n = 10).ResultsThe HIV-1 diversity of the PBMC-associated proviral quasispecies in EC was significantly (P < 0.01) lower than in VC, but not significantly different between PEC and EEC groups. We detected a considerable variation in the average pairwise nucleotide distance and proportion of unique sequences in the HIV-1 proviral quasispecies of PEC and EEC. Some PEC and EEC displayed highly homogenous proviral populations with large clusters of identical sequences, while others exhibited relatively diverse proviral populations with a high proportion of unique sequences comparable to VC subjects. The long-term (10–15 years) follow-up of the HIV-1 proviral populations revealed a complete evolutionary stasis in one PEC and measurable divergence rates in one EEC [3.1 (1.2–5.6) × 10−3 substitutions/site/year and one VC [2.9 (0.7–5.1) × 10−3 substitutions/site/year].ConclusionsThere is no simple relationship between systemic viral suppression and intra-host proviral diversity or rate of reservoir’s reseeding in chronically infected HIV controllers. Our results demonstrate that very divergent patterns of intra-host viral diversity and divergence could be detected in the setting of natural suppression of HIV-1 replication and that ongoing evolution and reseeding of the PBMC proviral reservoir occurs in some elite controllers.

The mitochondrial genome of pin-tailed snipe Gallinago stenura, and its implications for the phylogeny of Charadriiformes.

The Charadriiformes, among the most diverse orders of bird, is a good source to research on evolution. The mitochondrial genome sequencing database has rapidly increased in recent years, while Charadriiformes mitogenome has not been well studied. In this research, we determined the complete mitogenome sequence of Gallinago stenura, and comparatively analysed 20 mitogenomes of Charadriiformes. The mitogenomes display moderate size variation, and most of variation due to mutations in the control region. In 13 protein-coding genes, we found: 1. The GC skews are always negative, while the negative AT skews are found in 5 genes, 2. The average uncorrected pairwise distances reveal heterogeneity of evolutionary rate for each gene, 3. The ATG and TAA, respectively, are observed the most commonly start and stop codon. The highest dN/dS is detected for ATP8 (0.16) among Charadriiformes, while the lowest for COI (0.01), indicating that 13 protein-coding genes are evolving under the purifying selection. Predicted secondary structures of tRNAs indicate that the sequences and structures of anticodon, amino acceptor, and TψC arms are highly conserved, and most nucleotide variation is restricted to dihydrouridine arms with obvious indel polymorphisms. A total of 15 conserved sequence boxes were recognized in the control regions, and the 4 bp (5’-AAAC-3’) and 7 bp (5’- AAACAAC -3’) repeat sequences occurred frequently. Phylogenomic analysis based on the nearly complete mitochondrial genomes strongly supported the monophyly of the order, and the suborder Charadrii is at the basal of Charadriiformes. Moreover, our results well resolved the complexity family-level relationships and clearly depicted the evolutionary processes of Charadriiformes, based on 12 mitochondrial protein-coding genes from 18 families. This study improves our understanding of mitogenomic structure and evolution, which can provide further insights into our understanding of phylogeny and taxonomy in Charadriiformes.

Genetic diversity and signatures of selection in various goat breeds revealed by genome-wide SNP markers

BackgroundThe detection of signatures of selection has the potential to elucidate the identities of genes and mutations associated with phenotypic traits important for livestock species. It is also very relevant to investigate the levels of genetic diversity of a population, as genetic diversity represents the raw material essential for breeding and has practical implications for implementation of genomic selection. A total of 1151 animals from nine goat populations selected for different breeding goals and genotyped with the Illumina Goat 50K single nucleotide polymorphisms (SNP) Beadchip were included in this investigation.ResultsThe proportion of polymorphic SNPs ranged from 0.902 (Nubian) to 0.995 (Rangeland). The overall mean HO and HE was 0.374 ± 0.021 and 0.369 ± 0.023, respectively. The average pairwise genetic distance (D) ranged from 0.263 (Toggenburg) to 0.323 (Rangeland). The overall average for the inbreeding measures FEH, FVR, FLEUT, FROH and FPED was 0.129, −0.012, −0.010, 0.038 and 0.030, respectively. Several regions located on 19 chromosomes were potentially under selection in at least one of the goat breeds. The genomic population tree constructed using all SNPs differentiated breeds based on selection purpose, while genomic population tree built using only SNPs in the most significant region showed a great differentiation between LaMancha and the other breeds. We hypothesized that this region is related to ear morphogenesis. Furthermore, we identified genes potentially related to reproduction traits, adult body mass, efficiency of food conversion, abdominal fat deposition, conformation traits, liver fat metabolism, milk fatty acids, somatic cells score, milk protein, thermo-tolerance and ear morphogenesis.ConclusionsIn general, moderate to high levels of genetic variability were observed for all the breeds and a characterization of runs of homozygosity gave insights into the breeds’ development history. The information reported here will be useful for the implementation of genomic selection and other genomic studies in goats. We also identified various genome regions under positive selection using smoothed FST and hapFLK statistics and suggested genes, which are potentially under selection. These results can now provide a foundation to formulate biological hypotheses related to selection processes in goats.

MARS: improving multiple circular sequence alignment using refined sequences

BackgroundA fundamental assumption of all widely-used multiple sequence alignment techniques is that the left- and right-most positions of the input sequences are relevant to the alignment. However, the position where a sequence starts or ends can be totally arbitrary due to a number of reasons: arbitrariness in the linearisation (sequencing) of a circular molecular structure; or inconsistencies introduced into sequence databases due to different linearisation standards. These scenarios are relevant, for instance, in the process of multiple sequence alignment of mitochondrial DNA, viroid, viral or other genomes, which have a circular molecular structure. A solution for these inconsistencies would be to identify a suitable rotation (cyclic shift) for each sequence; these refined sequences may in turn lead to improved multiple sequence alignments using the preferred multiple sequence alignment program.ResultsWe present MARS, a new heuristic method for improving Multiple circular sequence Alignment using Refined Sequences. MARS was implemented in the C++ programming language as a program to compute the rotations (cyclic shifts) required to best align a set of input sequences. Experimental results, using real and synthetic data, show that MARS improves the alignments, with respect to standard genetic measures and the inferred maximum-likelihood-based phylogenies, and outperforms state-of-the-art methods both in terms of accuracy and efficiency. Our results show, among others, that the average pairwise distance in the multiple sequence alignment of a dataset of widely-studied mitochondrial DNA sequences is reduced by around 5% when MARS is applied before a multiple sequence alignment is performed.ConclusionsAnalysing multiple sequences simultaneously is fundamental in biological research and multiple sequence alignment has been found to be a popular method for this task. Conventional alignment techniques cannot be used effectively when the position where sequences start is arbitrary. We present here a method, which can be used in conjunction with any multiple sequence alignment program, to address this problem effectively and efficiently.

Characterization of N-linked glycosylation sites on envelope proteins of simian/human immunodeficiency virus in peripheral blood of Chinese rhesus macaques during acute infection

Objective: To investigate the number and distribution of N-linked glycosylation sites of simian/human immunodeficiency virus envelope proteins(SHIVSF162P3)and SHIV transmission. Methods: Two female adult Chinese rhesus macaques(4 years old)were intravenously inoculated with 300 TCID50 SHIVSF162P3. The macaques weighed 4 and 5 kg and were identified as Rh1 and Rh2. We collected plasma samples at days 3, 7, 10, 14, 17, 21, 24, 28, 35, 42, 49, 56, 63, 70 and 77 post-challenge. Subsequently, we monitored plasma viral load by real-time PCR after viral RNA isolation and cDNA synthesis. We amplified the full-length envelope gene by single genome amplification(SGA)at days 7, 14, 28 and 77. BioEdit, MEGA, and the HIV Databases were used to analyze envelope sequences. Sequence diversity and N-linked glycosylation sites were compared between virus stock and plasma viruses of the two macaques. Results: A total of 55 env sequences were obtained from virus stock and their average pairwise distances were(0.166 6± 0.096 3)%. Viral loads peaked at 7.68 and 7.49 log10 copies/ml at day 10 and reached the set point at day 42(4.27 and 4.81 log10 copies/ml). The percentages of envelope sequences containing 25 potential N-linked glycosylation sites(PNGSs)were 83%(20/24)and 94%(29/31)in Rh1 and Rh2, respectively, at day 7; these were significantly higher than the proportion in SHIVSF162P3 stock(49%(27/55)). Viral diversity after infection increased with time whereas the proportion of sequences containing 25 PNGSs decreased and sequences containing 27 PNGSs gradually increased. In Rh1, the percentage of sequences containing 27 PNGSs increased to 29% at day 28 and reached 35% at day 77 in Rh2. By analyzing the number of PNGSs in the V1-V5 regions, we found that PNGS variation mainly occurred in the V4 loop. Compared with sequences containing 27 PNGSs, a seven amino acid(TWNNTIG)deletion was found in the V4 loop, which resulted in a loss of two PNGSs at positions 392 and 396. Conclusion: Low glycosylation of the SHIVSF162P3 V4 loop may facilitate spread of the SHIV virus whereas viruses with highly glycosylated V4 loops showed replication advantages after infection.

Sequential CCR5-Tropic HIV-1 Reactivation from Distinct Cellular Reservoirs following Perturbation of Elite Control.

BackgroundHIV Elite Controllers may reveal insights into virus persistence given they harbour small reservoir sizes, akin to HIV non-controllers treated early with combination antiretroviral therapy. Both groups of patients represent the most promising candidates for interventions aimed at sustained remission or ‘cure’. Analytic treatment interruption (ATI) in the latter group leads to stochastic rebound of virus, though it is unclear whether loss of elite control is also associated with similar rebound characteristics.MethodsWe studied three discrete periods of virus rebound during myeloma related immune disruption over 2.5 years in an elite controller who previously underwent autologous stem cell transplantation (ASCT) in the absence of any antiretroviral therapy. Single genome sequencing of the V1-V4 region of env in PBMC and plasma was performed and phylogenies reconstructed. Average pairwise distance (APD) was calculated and non-parametric methods used to assess compartmentalisation. Coreceptor usage was predicted based on genotypic algorithms.Results122 single genome sequences were obtained (median 26 sequences per rebound). The initial rebounding plasma env sequences following ASCT represented two distinct lineages, and clustered with proviral DNA sequences isolated prior to ASCT. One of the lineages was monophyletic, possibly indicating reactivation from clonally expanded cells. The second rebound occurred 470 days after spontaneous control of the first rebound and was phylogenetically distinct from the first, confirmed by compartmentalisation analysis, with a different cellular origin rather than ongoing replication. By contrast, third rebound viruses clustered with second rebound viruses, with evidence for ongoing evolution that was associated with lymphopenia and myeloma progression. Following ASCT a shift in tropism from CXCR4-tropic viruses to a CCR5-tropic population was observed to persist through to the third rebound.ConclusionsOur data highlight similarities in the viral reservoir between elite and non-controllers undergoing ATI following allogeneic transplantation. The lack of propagation of CXCR4 using viruses following transplantation warrants further study.

Population Genomics Related to Adaptation in Elite Oat Germplasm.

Six hundred thirty five oat ( L.) lines and 4561 single-nucleotide polymorphism (SNP) loci were used to evaluate population structure, linkage disequilibrium (LD), and genotype-phenotype association with heading date. The first five principal components (PCs) accounted for 25.3% of genetic variation. Neither the eigenvalues of the first 25 PCs nor the cross-validation errors from = 1 to 20 model-based analyses suggested a structured population. However, the PC and = 2 model-based analyses supported clustering of lines on spring oat vs. southern United States origin, accounting for 16% of genetic variation ( < 0.0001). Single-locus -statistic () in the highest 1% of the distribution suggested linkage groups that may be differentiated between the two population subgroups. Population structure and kinship-corrected LD of = 0.10 was observed at an average pairwise distance of 0.44 cM (0.71 and 2.64 cM within spring and southern oat, respectively). On most linkage groups LD decay was slower within southern lines than within the spring lines. A notable exception was found on linkage group Mrg28, where LD decay was substantially slower in the spring subpopulation. It is speculated that this may be caused by a heterogeneous translocation event on this chromosome. Association with heading date was most consistent across location-years on linkage groups Mrg02, Mrg12, Mrg13, and Mrg24.

Robust time-series retrieval using probabilistic adaptive segmental alignment

Traditional pairwise sequence alignment is based on matching individual samples from two sequences, under time monotonicity constraints. However, in many application settings matching subsequences (segments) instead of individual samples may bring in additional robustness to noise or local non-causal perturbations. This paper presents an approach to segmental sequence alignment that jointly segments and aligns two sequences, generalizing the traditional per-sample alignment. To accomplish this task, we introduce a distance metric between segments based on average pairwise distances and then present a modified pair-HMM (PHMM) that incorporates the proposed distance metric to solve the joint segmentation and alignment task. We also propose a relaxation to our model that improves the computational efficiency of the generic segmental PHMM. Our results demonstrate that this new measure of sequence similarity can lead to improved classification performance, while being resilient to noise, on a variety of sequence retrieval problems, from EEG to motion sequence classification.