The human gut contains a complex microbiota dominated by bacteriophages but also containing other viruses and bacteria and fungi. There are a growing number of techniques for the extraction, ...sequencing, and analysis of the virome but currently no standardized protocols. This study established an effective workflow for virome analysis to investigate the virome of stool samples from two understudied ethnic groups from Malaysia: the Jakun and Jehai Orang Asli. By using the virome extraction and analysis workflow with the Oxford Nanopore Technology, long-read sequencing successfully captured close to full-length viral genomes. The virome composition of the two indigenous Malaysian communities were remarkably different from those found in other parts of the world. Additionally, plant viruses found in the viromes of these individuals were attributed to traditional food-seeking methods. This study establishes a human gut virome workflow and extends insights into the healthy human gut virome, laying the groundwork for comparative studies.
We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including ...single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree on the basis of binary single-nucleotide variants and projected the more complex variants onto it, estimating the number of mutations for each class. Our phylogeny shows bursts of extreme expansion in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations.
Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. ...Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease—causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.
Mountain gorillas are an endangered great ape subspecies and a prominent focus for conservation, yet we know little about their genomic diversity and evolutionary past. We sequenced whole genomes ...from multiple wild individuals and compared the genomes of all four Gorilla subspecies. We found that the two eastern subspecies have experienced a prolonged population decline over the past 100,000 years, resulting in very low genetic diversity and an increased overall burden of deleterious variation. A further recent decline in the mountain gorilla population has led to extensive inbreeding, such that individuals are typically homozygous at 34% of their sequence, leading to the purging of severely deleterious recessive mutations from the population. We discuss the causes of their decline and the consequences for their future survival.
The history of plants to be utilized as medicines is thousands of years old. Black cumin is one of the most widely examined plant possessing naturally occurring compounds with antimicrobial ...potential. Foliar application of growth stimulators is a successful strategy to enhance yield and quality in many crops. A field study was planned to apply growth stimulator like moringa leaf extract on black cumin crop grown under field conditions using RCB design with three replications. All other agronomic inputs and practices were uniform. The treatments were moringa leaf extract concentrations (10%, 20%), growth stages (40 days after sowing, 80 DAS, 120 DAS, 40 + 80 DAS, 40 + 120 DAS, 80 + 120 DAS, 40 + 80 + 120 days after sowing) and two controls unsprayed check (i.e. no moringa leaf extract, no water) and sprayed check (no moringa leaf extract + water). Application of 20% moringa leaf extract at stage-7 (40 + 80 + 120 days after sowing) had significantly increased plant height, branches plant
, essential oil content, fixed oil content, peroxidase value and iodine value of black cumin oil over unsprayed control. Application of moringa leaf extract showed maximum results and improves growth and yield of black cumin when applied at 40 + 80 + 120 days after sowing. As this study was only conducted using moringa leaf extract, it is advisable to conduct an experiment with various bio stimulants along with fertilizer combinations and growth regulators to check their synergistic effects for more reliable and acceptable recommendations in future.
The Kalash represent an enigmatic isolated population of Indo-European speakers who have been living for centuries in the Hindu Kush mountain ranges of present-day Pakistan. Previous Y-chromosomal ...and mitochondrial DNA markers provided no support for their claimed Greek descent following invasion of this region by Alexander III of Macedon and analysis of autosomal loci provided evidence of a strong genetic bottleneck. To understand their origins and demography further, we genotyped 23 unrelated Kalash samples on the Illumina HumanOmni 2.5M-8 BeadChip and sequenced one male individual at high coverage on an Illumina Hi-Seq 2000. Comparison with published data from ancient hunter-gatherers and European farmers show that the Kalash share drift with the Paleolithic Siberian hunter-gatherer and may represent an extremely drifted ancient North Eurasian population which also contributed to European and Near Eastern ancestry. Since the split from other South Asian populations the Kalash have maintained a low long-term effective population size (2,319-2,603) and experienced no detectable gene flow from their geographic neighbors in Pakistan or from other extant Eurasian populations. The mean time of divergence between Kalash and other populations currently residing in this region, was estimated to be 11.8 (10.6 -12.6) thousand years ago, and thus they represent present day descendants of some of the earliest migrants into the Indian sub-continent from West Asia.
The Americas were the last inhabitable continents to be occupied by humans, with a growing multidisciplinary consensus for entry 15–25 thousand years ago (kya) from northeast Asia via the former ...Beringia land bridge 1–4. Autosomal DNA analyses have dated the separation of Native American ancestors from the Asian gene pool to 23 kya or later 5, 6 and mtDNA analyses to ∼25 kya 7, followed by isolation (“Beringian Standstill” 8, 9) for 2.4–9 ky and then a rapid expansion throughout the Americas. Here, we present a calibrated sequence-based analysis of 222 Native American and relevant Eurasian Y chromosomes (24 new) from haplogroups Q and C 10, with four major conclusions. First, we identify three to four independent lineages as autochthonous and likely founders: the major Q-M3 and rarer Q-CTS1780 present throughout the Americas, the very rare C3-MPB373 in South America, and possibly the C3-P39/Z30536 in North America. Second, from the divergence times and Eurasian/American distribution of lineages, we estimate a Beringian Standstill duration of 2.7 ky or 4.6 ky, according to alternative models, and entry south of the ice sheet after 19.5 kya. Third, we describe the star-like expansion of Q-M848 (within Q-M3) starting at 15 kya 11 in the Americas, followed by establishment of substantial spatial structure in South America by 12 kya. Fourth, the deep branches of the Q-CTS1780 lineage present at low frequencies throughout the Americas today 12 may reflect a separate out-of-Beringia dispersal after the melting of the glaciers at the end of the Pleistocene.
•We sequenced 20 Native American Y chromosomes chosen for their genetic diversity•A Beringian Standstill of <4,600 years led to both Siberian and American Y-lineages•Y-lineage split times rule out occupation of the Americas before 19,500 years ago•Present-day male population structure in South America arose before 12,000 years ago
Pinotti et al. provide a genetic analysis of male history in the Americas that reveals three or four founding lineages, an occupation of Beringia for no longer than 4,600 years, entry south of the ice sheets after 19,500 years ago, and the establishment of the present-day male population structure in South America by 12,000 years ago.
Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to ...understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed GP , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages.
This study profiled the prevalence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) in the community and compared their resistome and genomic profiles with isolates from clinical ...patients through whole-genome sequencing.
Fecal samples from 233 community dwellers from Segamat, a town in southern Malaysia, were obtained between May through August 2018. Putative ESBL strains were screened and tested using antibiotic susceptibility tests. Additionally, eight clinical ESBL-EC were obtained from a hospital in the same district between June through October 2020. Whole-genome sequencing was then conducted on selected ESBL-EC from both settings (n = 40) for pan-genome comparison, cluster analysis, and resistome profiling.
A mean ESBL-EC carriage rate of 17.82% (95% CI: 10.48%- 24.11%) was observed in the community and was consistent across demographic factors. Whole-genome sequences of the ESBL-EC (n = 40) enabled the detection of multiple plasmid replicon groups (n = 28), resistance genes (n = 34) and virulence factors (n = 335), with no significant difference in the number of genes carried between the community and clinical isolates (plasmid replicon groups, p = 0.13; resistance genes, p = 0.47; virulence factors, p = 0.94). Virulence gene marker analysis detected the presence of extraintestinal pathogenic E. coli (ExPEC), uropathogenic E. coli (UPEC), and enteroaggregative E. coli (EAEC) in both the community and clinical isolates. Multiple blaCTX-M variants were observed, dominated by blaCTX-M-27 (n = 12), blaCTX-M-65 (n = 10), and blaCTX-M-15 (n = 9). The clinical and community isolates did not cluster together based on the pan-genome comparison, suggesting isolates from the two settings were clonally unrelated. However, cluster analysis based on carried plasmids, resistance genes and phenotypic susceptibility profiles identified four distinct clusters, with similar patterns between the community and clinical isolates.
ESBL-EC from the clinical and community settings shared similar resistome profiles, suggesting the frequent exchange of genetic materials through horizontal gene transfer.
In population genomics, polymorphisms that are highly differentiated between geographically separated populations are often suggestive of Darwinian positive selection. Genomic scans have highlighted ...several such regions in African and non-African populations, but only a handful of these have functional data that clearly associates candidate variations driving the selection process. Fine-Mapping of Adaptive Variation (FineMAV) was developed to address this in a high-throughput manner using population based whole-genome sequences generated by the 1000 Genomes Project. It pinpoints positively selected genetic variants in sequencing data by prioritizing high frequency, population-specific and functional derived alleles.
We developed a stand-alone software that implements the FineMAV statistic. To graphically visualise the FineMAV scores, it outputs the statistics as bigWig files, which is a common file format supported by many genome browsers. It is available as a command-line and graphical user interface. The software was tested by replicating the FineMAV scores obtained using 1000 Genomes Project African, European, East and South Asian populations and subsequently applied to whole-genome sequencing datasets from Singapore and China to highlight population specific variants that can be subsequently modelled. The software tool is publicly available at https://github.com/fadilla-wahyudi/finemav .
The software tool described here determines genome-wide FineMAV scores, using low or high-coverage whole-genome sequencing datasets, that can be used to prioritize a list of population specific, highly differentiated candidate variants for in vitro or in vivo functional screens. The tool displays these scores on the human genome browsers for easy visualisation, annotation and comparison between different genomic regions in worldwide human populations.
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