Biology subjects

Hamid, I.

Publications and source records attributed to Hamid, I..

6 recordsLinked to original sources

bioRxiv2026

Microtubule detyrosination enhances matrix remodeling and force transmission during endothelial sprouting

Angiogenic sprouting relies on the coordinated regulation of endothelial migration, force generation, and extracellular matrix (ECM) remodeling. While microtubules are known to regulate cell polarity and migration, how tubulin post-translational modifications reshape microtubule behavior and impact matrix-dependent migration programs remain unclear. Here, using sprouting angiogenesis as an integrative physiological context, we combine live-cell imaging, three-dimensional (3D) sprouting and microfluidic invasion assays, and 3D traction force microscopy to dissect the role of tubulin detyrosination and acetylation. We show that microtubule detyrosination, in contrast to acetylation, promotes directional persistence, sprout elongation and collective endothelial invasion. Detyrosinated microtubules remain dynamic and display more persistent growth, supporting sustained directional migration. Strikingly, microtubule detyrosination also enhances ECM remodeling, leading to increased matrix degradation and augmented traction force transmission. Functional inhibition experiments reveal that matrix degradation, rather than actomyosin contractility, is required for both elevated forces and enhanced sprouting. Together, these findings identify microtubule detyrosination as a key regulator linking cytoskeletal dynamics, cell migration and matrix remodeling during angiogenesis.

cell biology↗

bioRxiv2025

Transposable elements drive much of naturally occurring genetic lethality in Drosophila melanogaster

Recessive lethal mutations are widespread across studied species, with estimates suggesting that each individual carries at least one. Numerous lethal alleles persist in wild populations at higher frequencies than expected given their extreme deleterious nature. Though these findings spurred historical debate whether classical balancing selection maintains some lethal alleles at elevated frequencies (versus mutation-selection balance acting alone), we propose the question remained unanswered, especially given that the genetic basis of most naturally occurring lethal effects is still unknown. Given current genome-wide point mutation rate estimates, mutation-selection balance alone cannot explain some of this lethal variation in nature. However, evolutionary biologists have historically studied genetic variation through a lens of single nucleotide variants, when in fact the spectrum of mutational changes is far broader than point mutations alone, including indels, structural variants, short tandem repeats, and transposable element insertions. We uncover the genetic basis of lethality in nature and provide insight on the possible evolutionary forces allowing some to persist at higher frequencies. By locating hundreds of recessive lethal mutations in Drosophila melanogaster via complementation testing, fine-mapping, and sequencing a subset, we determine candidate lethal mutations in specific genes. We discover that many lethal disruptions are caused by transposable element insertions, potentially suggesting a higher mutation rate more compatible with mutation-selection balance. The most common transposable element in our data is estimated to have recently invaded D. melanogaster (between 2013-2016). This finding demonstrates that the many lethal alleles studied in D. melanogaster in the last century had a distinct genetic basis. Hence, we propose a model that could explain lethal variation in natural populations of D. melanogaster: lethal mutation frequencies are driven by invasions of new transposable elements and as time passes after each invasion, those frequencies decline as D. melanogaster evolves suppression mechanisms, allowing for natural selection to more efficiently remove lethal insertions. Upon the invasion of a new TE, the cycle repeats. The ubiquity of lethal alleles in natural populations is a classic conundrum for evolutionary geneticists for over a century, and this study utilized modern tools and sequencing technology to provide novel insight into this age-old mystery.

evolutionary biology↗

bioRxiv2025

Faroese Whole Genomes Provide Insight into Ancestry and Recent Selection

The Faroe Islands are home to descendants of a North Atlantic founder population with a unique history shaped by both migration and periods of relative isolation. Here, we investigate the genetic diversity, population structure, and demographic history of the islands by analyzing whole genome sequencing data from 40 participants in the Faroe Genome Project. This represents the first whole genome sequencing panel of this size from the Faroe Islands. We observed numerous putatively functional private alleles, including stop gain variants and high impact missense variants in the cohort. Faroese individuals had a higher proportion of their genomes contained in long runs of homozygosity than other European groups, including Finnish, suggesting a more recent or stronger bottleneck in the Faroese population. Signals of positive selection were identified at loci containing genes that play roles in vitamin D and dietary fat absorption and DNA repair, while increased diversity on lactase persistence haplotypes was observed. Fine-scale analysis of haplotype structure in present-day and ancient European genomes revealed genetic affinities with ancient Iron Age individuals from the North and West of Europe, providing evidence for potential contributions to the Faroese gene pool from Celtic and Viking populations as well as information about the temporal order in which these events happened. This study highlights the impact of evolutionary processes, such as ancient admixture, founder events, and positive selection, on the present-day genetic architecture of North Atlantic founder populations like the Faroe Islands.

genetics↗

bioRxiv2023

Whole-genome Studies of Malagasy People Uncover Novel Body Composition Associations

The majority of human genomic research studies have been conducted in European ancestry cohorts, at the loss of detecting potentially novel and globally impactful findings. Here, we present the first whole genome sequence data and genome-wide association study in a cohort of 264 Malagasy individuals from three locations on the island of Madagascar. We describe genetic variation in this Malagasy cohort, providing insight into the shared and unique patterns of genetic variation across the island. We observe phenotypic variation by location, and find high rates of hypertension particularly in the Southern Highlands as well as elevated malaria prevalence in the West Coast relative to other sites. We find a number of genetic associations with body composition traits, including many variants that are unique to African populations or populations with admixed African ancestry such as Madagascar. This study highlights the utility of including diverse populations in genomic research for the potential to gain novel insights, even with small cohort sizes. This project was conducted in partnership and consultation with local Malagasy stakeholders and serves as an example for equitable genomic research with potential impacts on our understanding of human health and disease.

genomics↗

bioRxiv2022

Localizing post-admixture adaptive variants with object detection on ancestry-painted chromosomes

Gene flow between previously isolated populations during the founding of an admixed or hybrid population has the potential to introduce adaptive alleles into the new population. If the adaptive allele is common in one source population, but not the other, then as the adaptive allele rises in frequency in the admixed population, genetic ancestry from the source containing the adaptive allele will increase nearby as well. Patterns of genetic ancestry have therefore been used to identify post-admixture positive selection in humans and other animals, including examples in immunity, metabolism, and animal coloration. A common method identifies regions of the genome that have local ancestry outliers compared to the distribution across the rest of the genome, considering each locus independently. However, we lack theoretical models for expected distributions of ancestry under various demographic scenarios, resulting in potential false positives and false negatives. Further, ancestry patterns between distant sites are often not independent. As a result, current methods tend to infer wide genomic regions containing many genes as under selection, limiting biological interpretation. Instead, we develop a deep learning object detection method applied to images generated from local ancestry-painted genomes. This approach preserves information from the surrounding genomic context and avoids potential pitfalls of user-defined summary statistics. We find the-method is robust to a variety of demographic misspecifications using simulated data. Applied to human genotype data from Cabo Verde, we localize a known adaptive locus to a single narrow region compared to multiple or long windows obtained using two other ancestry-based methods.

genomics↗

bioRxiv2020

Rapid adaptation to malaria facilitated by admixture in the human population of Cabo Verde

Humans have undergone large migrations over the past hundreds to thousands of years, exposing ourselves to new environments and selective pressures. Yet, evidence of ongoing or recent selection in humans is difficult to detect. Many of these migrations also resulted in gene flow between previously separated populations. These recently admixed populations provide unique opportunities to study rapid evolution in humans. Developing methods based on distributions of local ancestry, we demonstrate that this sort of genetic exchange has facilitated detectable adaptation to a malaria parasite in the admixed population of Cabo Verde within the last [~]20 generations. We estimate the selection coefficient is approximately 0.08, one of the highest inferred in humans. Notably, we show that this strong selection at a single locus has likely affected patterns of ancestry genome-wide, potentially biasing demographic inference. Our study provides evidence of adaptation in a human population on historical timescales.

evolutionary biology↗