Biology subjects

Ayub, Q.

Publications and source records attributed to Ayub, Q..

11 recordsLinked to original sources

bioRxiv2026

Shared antimicrobial resistance gene families across gut microbiomes in indigenous Orang Asli communities of Peninsular Malaysia

Indigenous groups across the world have been underrepresented in the ongoing efforts to map human microbiome diversity. This study investigates the gut microbiome and resistome diversities of Indigenous Orang Asli communities in Malaysia with different lifestyles and degree of urbanisation. Healthy adult participants (>18 years old) were recruited from three Indigenous communities - Temuan (urban), Temiar (semi-urban), and Jahai (rural hunter-gatherer), as well as urban Malays. Stool samples were collected on dry ice and analysed using shotgun metagenomic sequencing. Microbial alpha diversity (Shannon) decreased but antibiotic resistance genes (ARGs) diversity increased as the degree of urbanisation in the groups increased (P < 0.05). The groups contributed to 13% of the variation observed in the microbial composition (PERMANOVA, P = 0.001), and 14.5% in resistome composition (PERMANOVA, P = 0.001). Romboutsia timonensis was significantly depleted in Jahai compared to Malay (FDR = 0.04). Shared ARGs conferring resistance to beta-lactams (cfxA), tetracyclines (tet), and macrolides (erm) were observed across all groups, irrespective of geographical location, ethnicity and lifestyle. This study provides initial characterisation of the gut microbiome and resistome of three Indigenous Orang Asli communities in Malaysia. Our findings offer foundational evidence of antimicrobial resistance patterns and underscores the need for broader inclusion of underrepresented populations in national surveillance and stewardship efforts. Impact statementOur study generated one of the first integrated microbiome-resistome analyses across an urbanisation gradient of Malaysian gut microbiome. Shotgun metagenomic profiling of hard-to-access Indigenous cohorts enabled taxonomic classification for most reads, supporting high-resolution microbial community and ARG analysis. Increasing urbanisation was associated with reduced microbial alpha diversity alongside increased ARG diversity, with population grouping explaining an insightful proportion of both microbiome and resistome variation. Core resistance determinants to beta-lactams (cfxA), tetracyclines (tet), and macrolides (erm) were consistently detected across lifestyles and geographies. These results establish a baseline framework for urbanisation-linked microbial shifts in the under-studied Malaysian gut microbiome and provide actionable direction for investigating national AMR drivers, surveillance design, and targeted stewardship strategies in underrepresented populations. Data summary and code availabilitySupporting data are provided in the supplementary data files. Specific accession numbers of the sequence data are provided as Supplementary Material. Codes produced for this analysis can be found at https://zenodo.org/records/18208358.

genomics↗

bioRxiv2024

Identification of novel prophages and variants of Integrative and Conjugative Elements in Elizabethkingia anophelis clinical isolates from Seremban, Malaysia

Elizabethkingia anophelis is an emerging multidrug-resistant pathogen that has been identified globally, including in Malaysia. In this study, we used the Oxford Nanopore Technologies (ONT) long-read platform to generate the complete genome sequences of seven clinical isolates of E. anophelis from a tertiary hospital in the city of Seremban, located in the state of Negeri Sembilan in Peninsular Malaysia. These sequences were analysed alongside over 400 publicly available E. anophelis genomes from other countries. Three of the seven E. anophelis isolates, Eli4, Eli5, and Eli6, were almost identical and their isolation over a period of six weeks from the same hospital was suggestive of nosocomial transmission. Besides these three isolates, the other E. anophelis isolates were genetically diverse and related to distinct isolates from other countries. No plasmids were identified in the genomes of all seven E. anophelis isolates. A novel 39,686 bp prophage was identified in the genome of E. anophelis Eli4 while a presumptive incomplete prophage was found in the genomes of Eli2, Eli4, Eli5 and Eli6. E. anophelis genomes are notable for possessing integrative and conjugative elements (ICEs), which enable the bacterium to acquire new genes, including those encoding antimicrobial resistance or virulence. Several novel ICE sequences were discovered in the Seremban E. anophelis genomes, and this includes an ICE found in Eli8, designated Eli8_ICE1, which encodes phage defence genes such as type I restriction-modification systems, a bacterial cyclic oligonucleotide-based anti-phage signalling system (CBASS) and prokaryotic argonaute systems. The latter two phage defence genes have so far not been reported in the E. anophelis genome. This study demonstrates the utility of long-read sequencing in assessing the diversity and plasticity of E. anophelis genomes and emphasises further research into the role of ICEs in phage defence systems and their potential impact on antimicrobial treatment and phage therapy. RepositoriesThe Elizabethkingia anophelis genomes in this study have been deposited in the NCBI database under BioProject PRJNA1175025.

microbiology↗

bioRxiv2024

Partitioning the genomic journey to becoming Homo sapiens

What makes us human? Homo sapiens diverged from its ancestors in fundamental ways, as reflected in recent genomic acquisitions, such as the PAR2-Y chromosome translocation. Here we show that despite morphological and cultural differences between modern and archaic humans, these human groups share these recent acquisitions. Our modern lineage shows recent functional variants in only 56 genes, of which 24 are linked to brain functions and skull morphology. Nevertheless, these acquisitions failed to introgress into Neanderthals when archaic and modern populations admixed after 350 kya, suggesting their exclusive link to the modern human niche or that Neanderthals small population size hindered their spread. Taken together, our results point to a scenario where Modern and Archaic should be regarded as populations of an otherwise common human species, which independently accumulated mutations and cultural innovations.

evolutionary biology↗

bioRxiv2024

Himalayan whole-genome sequences provide insight into population formation and adaptation

High-altitude environments pose substantial challenges for human survival and reproduction, attracting considerable attention to the demographic and adaptive histories of high-altitude populations. Previous work focused mainly on Tibetans, establishing their genetic relatedness to East Asians and their genetic adaptation to high altitude, especially at EPAS1. Here, we present 87 new whole-genome sequences from 16 Himalayan populations and the insight they provide into the genomic history of the region. We show that population structure in the Himalayas began to emerge as early as 10,000 years ago, predating archaeological evidence of permanent habitation above 2,500 meters by approximately 6,000 years. The high prevalence of the introgressed adaptive EPAS1 haplotype in all high-altitude populations today supports a shared genetic origin and its importance for survival in this region. We also identify additional selection signals in genes associated with hypoxia, physical activity, immunity and metabolism which could have facilitated adaptation to the harsh environment. Over time, increasing genetic structure led to the diverse and strongly differentiated ethnic groups observed today, most of which maintained small population sizes throughout their history or experienced severe bottlenecks. Between 6,000 and 3,000 years ago, a few uniparental lineages became predominant, likely coinciding with the advent of agriculture, although significant population growth was not observed in the Himalayas except in the Tibetans. In more recent times, we detect bidirectional gene flow between high-altitude and lowland groups, occurring on both sides of the Himalayan range. The timing of this admixture aligns with the rise and expansion of historical regional powers, particularly during the Tibetan Empire and the northern Indian Gupta Empire. In the past few centuries, migrations to the Himalayas seem to have occurred alongside conflicts and population displacements in nearby regions and show some sex bias.

genomics↗

bioRxiv2023

Genomic, genetic and phylogenetic evidence for a new falcon species using chromosome-level genome assembly of the gyrfalcon and population genomics

The taxonomic classification of a falcon population found in the Altai region in Asia has been heavily debated for two centuries and previous studies have been inconclusive, hindering a more informed conservation approach. Here, we generated a chromosome-level gyrfalcon reference genome using the Vertebrate Genomes Project (VGP) assembly pipeline. Using whole genome sequences of 44 falcons from different species and populations, including "Altai" falcons, we analyzed their population structure, admixture patterns and demographic history. We find that the Altai falcons are genomically mosaic of saker and gyrfalcon ancestries, and carry distinct W- and mitochondrial-haplotypes that cluster with the lanner falcon. The Altai haplotype diverged 422,000 years ago from the ancestor of sakers and gyrfalcons, both of which, in turn, split 109,000 years ago. The Altai W chromosome includes coding variants that may influence important structural, behavioral and reproductive traits. These findings support the designation of Altai falcons as a distinct falcon species (Falco altaicus).

genomics↗

bioRxiv2022

Ghost admixture in eastern gorillas

Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic ghost lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.

evolutionary biology↗

bioRxiv2020

A fluoroquinolone-sensitive Shigella sonnei UKMCC1015 downregulates the expression of ribosomal proteins in response to sub-lethal concentration of norfloxacin

1.Shigella causes shigellosis that requires antibiotic treatment in severe cases. Sub-lethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unknown. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a norfloxacin-sensitive strain, Shigella sonnei UKMCC1015. Firstly, the whole genome of S. sonnei UKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. However, transcriptomic analysis showed that low NOR levels do not change the expression of AMR genes and norfloxacin targets. Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated ppGpp levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase (relA). However, high levels of ppGpp (due to relA overexpression) are detrimental to the continued survival of S. sonnei during prolonged exposure to NOR. This study revealed that a norfloxacin-sensitive strain responds differently to sub-lethal NOR than commonly reported in resistant strains. Overexpression of relA (high ppGpp levels) may reduce the mutability of S. sonnei UKMCC1015 in response to NOR exposure and affect NOR tolerance.

microbiology↗

bioRxiv2019

Genomic characterization of Vibrio parahaemolyticus from Pacific white shrimp and rearing water reveals novel sequence types and multiple introductions of Photorhabdus insect-related (Pir) toxin-like genes into Malaysia

The Malaysian and global shrimp aquaculture production has been significantly impacted by acute hepatopancreatic necrosis disease (AHPND) typically caused by Vibrio parahaemolyticus harboring the pVA plasmid containing the pirAVpand pirBVpgenes which code for Photorhabdus insect-related (Pir) toxin. The limited genomic resource for V. parahaemolyticus strains from Malaysian aquaculture farms precludes an in-depth understanding of their diversity and evolutionary relationships. In this study, we isolated shrimp-associated and environmental (rearing water) V. parahaemolyticus from three aquaculture farms located in Northern and Central Malaysia followed by whole-genome sequencing of 40 randomly selected isolates on the Illumina MiSeq. Phylogenomic analysis and multilocus sequence typing (MLST) reveal distinct lineages of V. parahaemolyticus that harbor the pirABVpgenes. The recovery of pVA plasmid backbone devoid of pirAVp or pirABVp in some V. parahaemolyticus isolates suggests that the toxin genes are prone to deletion. The new insight gained from phylogenomic analysis of Asian V. parahaemolyticus, in addition to the observed genomic instability of pVa plasmid, will have implications for improvements in aquaculture practices to diagnose, treat or limit the impacts of this disease.

microbiology↗

bioRxiv2019

Insights into human genetic variation and population history from 929 diverse genomes

Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented private genetic variation in southern and central Africa and in Oceania and the Americas, but an absence of fixed, private variants between major geographical regions. We also find deep and gradual population separations within Africa, contrasting population size histories between hunter-gatherer and agriculturalist groups in the last 10,000 years, a potentially major population growth episode after the peopling of the Americas, and a contrast between single Neanderthal but multiple Denisovan source populations contributing to present-day human populations. We also demonstrate benefits to the study of population relationships of genome sequences over ascertained array genotypes. These genome sequences are freely available as a resource with no access or analysis restrictions.

genomics↗

bioRxiv2018

Positive selection in Europeans and East-Asians at the ABCA12 gene

Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation.\n\nWe confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and frequent among non-Africans already 45,000 years ago.

genomics↗

bioRxiv2017

Like Sugar in Milk: Reconstructing the genetic history of the Parsi population

BackgroundThe Parsis, one of the smallest religious community in the world, reside in South Asia. Previous genetic studies on them, although based on low resolution markers, reported both Iranian and Indian ancestries. To understand the population structure and demographic history of this group in more detail, we analyzed Indian and Pakistani Parsi populations using high-resolution autosomal and uniparental (Y-chromosomal and mitochondrial DNA) markers. Additionally, we also assayed 108 mitochondrial DNA markers among 21 ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India.\n\nResultsOur extensive analyses indicated that among present-day populations, the Parsis are genetically closest to Middle Eastern (Iranian and the Caucasus) populations rather than their South Asian neighbors. They also share the highest number of haplotypes with present-day Iranians and we estimate that the admixture of the Parsis with Indian populations occurred [~]1,200 years ago. Enriched homozygosity in the Parsi reflects their recent isolation and inbreeding. We also observed 48% South-Asian-specific mitochondrial lineages among the ancient samples, which might have resulted from the assimilation of local females during the initial settlement.\n\nConclusionsWe show that the Parsis are genetically closest to the Neolithic Iranians, followed by present-day Middle Eastern populations rather than those in South Asia and provide evidence of sex-specific admixture from South Asians to the Parsis. Our results are consistent with the historically-recorded migration of the Parsi populations to South Asia in the 7thcentury and in agreement with their assimilation into the Indian sub-continents population and cultural milieu \"like sugar in milk\". Moreover, in a wider context our results suggest a major demographic transition in West Asia due to Islamic-conquest.

evolutionary biology↗