Biology subjects

Chakraborty, M.

Publications and source records attributed to Chakraborty, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

SAXS/MC studies of the mixed-folded protein Cdt1 reveal monomeric, folded over conformations

Cdt1 is a protein critical for DNA replication licensing and is well-established to be a binding partner of the minichromosome maintenance (MCM) complex. Cdt1 has also been demonstrated to have an emerging, "moonlighting" role at the kinetochore via direct binding to microtubules and to the Ndc80 complex. However, it is not known how the structure and conformations of Cdt1 could allow for these multiple, completely unique sets of protein complexes. And while there exist multiple robust methods to study entirely folded or entirely unfolded proteins, structure-function studies of combined, mixed folded/disordered proteins remain challenging. It this work, we employ multiple orthogonal biophysical and computational techniques to provide a detailed structural characterization of human Cdt1 92-546. DSF and DSCD show both folded winged helix (WH) domains of Cdt1 are relatively unstable. CD and NMR show the N-terminal and the linker regions are intrinsically disordered. Using DLS and SEC-MALS, we show that Cdt1 is polydisperse, monomeric at high concentrations, and without any apparent inter-molecular self-association. SEC-SAXS of the monomer in solution enabled computational modeling of the protein in silico. Using the program SASSIE, we performed rigid body Monte Carlo simulations to generate a conformational ensemble. Using experimental SAXS data, we filtered for conformations which did and did not fit our data. We observe that neither fully extended nor extremely compact Cdt1 conformations are consistent with our SAXS data. The best fit models have the N-terminal and linker regions extended into solution and the two folded domains close to each other in apparent "folded over" conformations. The best fit Cdt1 conformations are consistent with a function as a scaffold protein which may be sterically blocked without the presence of binding partners. Our studies also provide a template for combining experimental and computational biophysical techniques to study mixed-folded proteins.

biophysics↗

bioRxiv2023

Interactions between the gut microbiome, dietary restriction, and aging in genetically diverse mice

The intestinal microbiome changes with age, but the causes and consequences of microbiome aging remain unclear. Furthermore, the gut microbiome has been proposed to mediate the benefit of lifespan- extending interventions such as dietary restriction, but this hypothesis warrants further exploration. Here, by analyzing 2997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice, we provide new insights into the interplay between the microbiome, aging, dietary restriction, host genetics, and a wide range of health parameters. First, we find that microbiome uniqueness increases with age across datasets and species. Moreover, age-associated changes are better explained by cumulative exposure to stochastic events (neutral theory) than by the influence of an aging host (selection theory). Second, we unexpectedly find that the majority of microbiome features are significantly heritable and that the amount of variation explained by host genetics is as large as that of aging and dietary restriction. Third, we find that the intensity of dietary restriction parallels the extent of microbiome changes and that dietary restriction does not rejuvenate the microbiome. Lastly, we find that the microbiome is significantly associated with multiple health parameters -- including body composition, immune parameters, and frailty -- but not with lifespan. In summary, this large and multifaceted study sheds light on the factors influencing the microbiome and aspects of host physiology modulated by the microbiome.

microbiology↗

bioRxiv2023

Increasing equity in science requires better ethics training: a course by trainees, for trainees

Despite the profound impacts of scientific research, few scientists have received the necessary training to productively discuss the ethical and societal implications of their work. To address this critical gap, we - a group of predominantly human genetics trainees - developed a course on genetics, ethics, and society. We intend for this course to serve as a template for other institutions and scientific disciplines. Our curriculum positions human genetics within its historical and societal context and encourages students to evaluate how societal norms and structures impact the conduct of scientific research. We demonstrate the utility of this course via surveys of enrolled students and provide resources and strategies for others hoping to teach a similar course. We conclude by arguing that if we are to work towards rectifying the inequities and injustices produced by our field, we must first learn to view our own research as impacting and being impacted by society.

genetics↗

bioRxiv2023

Nuclear lamin A-associated proteins are required for centromere assembly

Many Lamin A-associated proteins (LAAPs) that are key constituents of the nuclear envelope (NE), assemble at the "core" domains of chromosomes during NE reformation and mitotic exit. However, the identity and function of the chromosomal core domains remain ill-defined. Here, we show that a distinct section of the core domain overlaps with the centromeres/kinetochores of chromosomes during mitotic telophase. The core domain can thus be demarcated into a kinetochore proximal core (KPC) on one side of the segregated chromosomes and the kinetochore distal core (KDC) on the opposite side, close to the central spindle. We next tested if centromere assembly is connected to NE re-formation. We find that centromere assembly is markedly perturbed after inhibiting the function of LMNA and the core-localized LAAPs, BANF1 and Emerin. We also find that the LAAPs exhibit multiple biochemical interactions with the centromere and inner kinetochore proteins. Consistent with this, normal mitotic progression and chromosome segregation was severely impeded after inhibiting LAAP function. Intriguingly, the inhibition of centromere function also interferes with the assembly of LAAP components at the core domain, suggesting a mutual dependence of LAAP and centromeres for their assembly at the core domains. Finally, we find that the localization of key proteins involved in the centromeric loading of CENP-A, including the Mis18 complex and HJURP were markedly affected in LAAP-inhibited cells. Our evidence points to a model where LAAP assembly at the core domain serves a key function in loading new copies of centromeric proteins during or immediately after mitotic exit.

cell biology↗

bioRxiv2023

B Cells Promote T Cell Immunosenescence and Mammalian Aging Parameters

A dysregulated adaptive immune system is a key feature of aging, and is associated with age-related chronic diseases and mortality. Most notably, aging is linked to a loss in the diversity of the T cell repertoire and expansion of activated inflammatory age-related T cell subsets, though the main drivers of these processes are largely unknown. Here, we find that T cell aging is directly influenced by B cells. Using multiple models of B cell manipulation and single-cell omics, we find B cells to be a major cell type that is largely responsible for the age-related reduction of naive T cells, their associated differentiation towards pathogenic immunosenescent T cell subsets, and for the clonal restriction of their T cell receptor (TCR). Accordingly, we find that these pathogenic shifts can be therapeutically targeted via CD20 monoclonal antibody treatment. Mechanistically, we uncover a new role for insulin receptor signaling in influencing age-related B cell pathogenicity that in turn induces T cell dysfunction and a decline in healthspan parameters. These results establish B cells as a pivotal force contributing to age-associated adaptive immune dysfunction and healthspan outcomes, and suggest new modalities to manage aging and related multi-morbidity. One Sentence SummaryInsulin receptor signaling facilitates the induction of age associated B cell inflammatory changes, which drive phenotypic aging of the T cell compartment and adverse outcomes to mammalian healthspan parameters.

immunology↗

bioRxiv2023

Wound induced small-peptide mediated signalling cascade regulated by OsPSKR, dictates balance between growth and defense in rice

Wounding is a general stress in plants that results from various pest and pathogenic infections in addition to environment induced mechanical damages. Plants have sophisticated molecular mechanisms to recognize and respond to pests and pathogens. Although several molecules such as phytohormones, peptides and receptors have been attributed to wound responses in dicots, such mechanisms for monocots probably having distinct wound responses are less understood. Here, we show the involvement of two distinct categories of temporally separated, endogenously derived peptides, namely, plant elicitor peptides (PEPs) and phytosulfokine (PSK), that mediate wound responses in rice. These peptides trigger a dynamic signal relay in which a novel receptor kinase named OsPSKR played a major role. OsPSKR perceived PSK ligand, acting in association with a co-receptor OsSERK1, to activate downstream responses in a kinase activity-dependent manner. Perturbation of OsPSKR expression in rice led to compromised development and constitutive autoimmune phenotypes. These results suggested that OsPSKR maintains the trade-off between growth and exaggerated defense responses, both during homeostasis and wounding. Collectively, these findings indicate the presence of a stepwise peptide-mediated signal relay that regulates the transition from defense to growth upon wounding in monocots. One line summaryEndogenous peptide signalling initiated wound responses through a receptor-like kinase OsPSKR to maintain the balance between growth and defense responses.

plant biology↗

bioRxiv2023

Oncogenic reactivation of young L1s is a hallmark of colon cancer

Transposable elements become increasingly active in both cancerous and aging cells, driven by loss of DNA methylation as cells divide. Here we leverage the epigenomes of colon cancers with matched adjacent tissue, in addition to non-cancerous normals and cell line models, to assess the role of transposable elements as drivers or passengers in cancer development. Using the baseline of activity from normal and adjacent tissue, we show that the youngest subfamilies of the LINE1 (L1) family exhibit a degree of activity and recurrence across patients that goes beyond what is expected from hypomethylation and cell division, suggesting an additional mechanism of oncogenic reactivation. We characterize this mechanism and find that the loss of the tumor suppressor PLZF drives young L1 reactivation in a cell-division-independent manner. PLZF de-repression exposes abundant motifs for tumor core factors in the L1 5UTR. Active young L1s act as oncogenic enhancers, interacting with oncogenes via gained chromatin loops. We uncover oncogenic L1 reactivation as a hallmark of colon cancer, where young L1s activate universally in our cohort at high levels of recurrence, act as enhancers to oncogenes, and become wired into the core regulatory circuitry of colon cancer.

genomics↗

bioRxiv2022

Phanta: Phage-inclusive profiling of human gut metagenomes

The human gut microbiome is a diverse ecosystem that encompasses multiple domains of life and plays a vital role in human health. Due to technical limitations, most microbiome studies have focused on gut prokaryotes, overlooking bacteriophages and other gut viruses. The most common method to profile viruses is to assemble shotgun metagenomic reads - often from virus-enriched samples - and identify viral genomes de novo. While valuable, this resource-intensive and reference-independent method has limited sensitivity. To overcome these drawbacks, we developed Phanta, which profiles human gut metagenomes in a virus-inclusive manner directly from short reads utilizing recently published catalogs of gut viral genomes. Phanta incorporates k-mer based classification tools and was developed with virus-specific properties in mind. Specifically, it includes optimizations considering viruses small genome size, sequence homology with prokaryotes, and interactions with other members of the gut microbial community. Based on simulations, the workflow is fast and accurate with respect to both prokaryotes and viruses, minimizing false positive species identification using a novel genome coverage-based strategy. When applied to metagenomes from healthy adults, Phanta identified ~200 viral species per sample, ~5x more than the standard assembly-based methods. Notably, we observed a 2:1 ratio between gut viruses and bacteria, with higher interindividual variability of the gut virome compared to the gut bacteriome. Phanta performs equally well on bulk vs. virus-enriched metagenomes, making it possible to study prokaryotes and viruses in a single experiment, with a single analysis. Phanta can tandemly profile gut viruses and prokaryotes in existing and novel datasets, and can therefore identify cross-domain interactions with likely relevance to human health. We expect that Phanta will reduce the barrier to virus-inclusive studies of the human gut microbiome, thus making it standard practice.

genomics↗

bioRxiv2022

Sex-linked gene traffic underlies the acquisition of sexually dimorphic UV color vision in Heliconius butterflies

Butterflies have photoreceptor cells that are sensitive to the ultraviolet part of the spectrum due to ultraviolet-sensitive rhodopsin (UVRh), a gene that has been duplicated in the Heliconius genus. In individuals expressing UVRh1 and UVRh2, electrophysiological and behavioral studies demonstrate that these opsin proteins enable discrimination of UV wavelengths. This behavioral trait varies between species, being absent in H. melpomene and limited to females in H. erato. To identify the evolutionary origins of this trait, we first examined UV color vision in H. charithonia, a species related to H. erato in the sara/sapho group. We found that this species also has sexually dimorphic UV color vision. To identify the genetic basis of this trait, we built a reference-grade genome assembly of H. charithonia. We discovered that one duplicate, UVRh1, is present on the W chromosome, making it obligately female-specific. We employed gDNA PCR assays of UVRh1 across the Heliconius genus. In species with sexually dimorphic UVRh1 mRNA expression, UVRh1 gDNA is absent in males, whereas in species with sexually monomorphic UVRh1 mRNA expression, UVRh1 gDNA is found in both sexes. The presence or absence of male UVRh1 expression across the Heliconius phylogeny supports a model where sexual dimorphism was acquired early via movement of a gene duplication to the W-chromosome. We used CRISPR-Cas9 to engineer a deletion in the UVRh1 locus in female H. charithonia and use immunohistochemistry to show that UVRh1 protein expression is absent in mutant tissue, similar to that of males. Our results show that a rare behavioral phenotype, sex-specific UV color vision, was acquired via sex chromosome gene traffic of a duplicated UV rhodopsin.

evolutionary biology↗

bioRxiv2022

The Ndc80-Cdt1-Ska1 complex constitute a minimal processive kinetochore-microtubule coupling unit

The Ndc80 kinetochore complex is essential for robust kinetochore-microtubule (k-MT) attachments during mitosis. Ndc80 has been shown to recruit the Ska1 complex to kinetochores, where Ska1 is thought to aid in k-MT coupling by Ndc80. Our previous work has shown that Cdt1, a DNA replication licensing factor, is a novel mitotic spindle-associated protein that is also recruited to kinetochores via Ndc80 and is required for stabilizing k-MT attachments. In this study, we developed auxin-induced degron (AID)-tagging to validate the previously demonstrated mitotic role of Cdt1. We demonstrate a direct interaction between Cdt1 and Ska1 that is essential for proper recruitment of Cdt1 to kinetochores and spindle microtubules. We find that Cdk1dependent phosphorylation of Cdt1 during mitosis is critical for Ska1-binding, consequently regulating the stabilization of metaphase k-MT attachments and normal mitotic progression. Total internal reflection fluorescence microscopy (TIR-FM) experiments reveal that Cdt1 synergizes with the Ndc80 and the Ska1 complexes for microtubule-binding. Further, we show that single Cdt1 molecules form diffusive tripartite complexes with Ndc80 and Ska1 that can processively track the ends of dynamic microtubules in vitro. Taken together our data identifies a minimal molecular unit responsible for bidirectional processive tip tracking of kinetochores.

cell biology↗

bioRxiv2022

Assessment of local potato cultivars found in Cis-Himalayan region of West Bengal through morphology and biochemical profiling

Potato is a major global food crop grown for tubers (underground storage stems) that are high in carbohydrates, minerals, and vitamins. The presence of anthocyanins in tuber skin and flesh can have a significant impact on customer preferences. Potatoes are also high in resistant starches, which have a variety of health benefits, including enhanced fullness, cholesterol reduction, and a reduced risk of colon cancer etc. In West Bengal, diabetes is prevalent. Similarly, according to ICMR studies, colon cancer affects 8.9% of all cancer patients in West Bengal cancer which is caused by ill eating habits or the consumption of foods that are low in antioxidants. 5-10% of colon cancers are genetically caused, while the remainder are caused by poor eating habits or the consumption of foods that are low in antioxidants. To address these issues, one strategy is to eat foods with a low glycemic index and high antioxidant content as a staple food. The tuber tissues of the potato (S. tuberosum L.) accumulate various quantities of anthocyanins, which are commonly consumed around the world. Anthocyanins are pigments that range in colour from red to purple and are found throughout the plant kingdom. Anthocyanins are powerful antioxidants that are water soluble. The red skin potato is well-known among the general public. The epidermal layer contains a high quantity of red anthocyanins, which causes the skin to be red. With this background the present study has been undertaken to address the following objectives morphological (quantitative and qualitative traits) and biochemical characterization of local potato cultivars and identification of most stable genotypes based on the anthocyanin content and tuber yield of local potato cultivars. For our recent research 14 local potato cultivar from North Bengal were collected and evaluated for DUS characterization showed wide range of variability with respect to different phenotypic variants of ten characters. Overall predominant DUS characters of local potato cultivars found in North Bengal are medium sized apical length of sprout, short stem height, compact foliage structure, open leaf structure, ovate lanceolate type leaflet shape, purple leaf sprout predominant colour, spherical leaf sprout shape, medium intensity of anthicyanin coloraton at the base, light intensity of anthicyanin coloraton at the tip and weak nature of light sprout pubescence base. The results of the present investigation suggest that local potato cultivars collected from the northern part of West Bengal showed a high level of genetic variation. The differences between genotypes were highly significant at the 1% and 5% alpha level for all characters like tuber yield, length and weight of tuber, length of sprout, chlorophyll content, canopy temperature, and number of tuber per plant, according to the analysis of variance. Three quantitative traits namely tuber yield, tuber breadth, tuber length played major role in the genetic variance. Anthocyanin content had more contribution to diversify the local potato cultures according to biochemical characterization AMMI analysis suggested that Jalpai from CoochBehar is the most stable potato cultivars in respect to anthocyanin content and tuber yield per plant.

plant biology↗

bioRxiv2022

CLASP2 stabilizes GDP-associated terminal tubulins to prevent microtubule catastrophe

CLASPs are ubiquitous stabilizers of microtubule dynamics but their molecular targets at the microtubule plus-end are not understood. Using DNA origami-based reconstructions we show that clusters of human CLASP2 form a load-bearing bond with terminal GDP-tubulins at the stabilized microtubule tip. This activity relies on the unconventional TOG2 domain of CLASP2, which releases its high-affinity bond with the GDP-dimers upon their conversion into polymerization-competent GTP-tubulin. By tethering dynamic microtubule ends near immobilized CLASP2, we show that the targets for CLASP2 binding at the polymerizing tip arise stochastically, leading to nanoscale disruptions in microtubule tip integrity. The ability of CLASP2 to recognize nucleotide-specific tubulin conformation and stabilize the catastrophe-promoting GDP-tubulins intertwines with the previously underappreciated exchange between GDP and GTP at terminal tubulins, providing a distinct molecular mechanism to suppress microtubule catastrophe without affecting tubulin incorporation.

biophysics↗

bioRxiv2021

Small molecule v-ATPase inhibitor Etidronate lowers levels of ALS protein ataxin-2

Antisense oligonucleotide therapy targeting ATXN2--a gene in which mutations cause neurodegenerative diseases spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis--has entered clinical trials in humans. Additional methods to lower ataxin-2 levels would be beneficial not only in uncovering potentially cheaper or less invasive therapies, but also in gaining greater mechanistic insight into how ataxin-2 is normally regulated. We performed a genome-wide fluorescence activated cell sorting (FACS)-based CRISPR screen in human cells and identified multiple subunits of the lysosomal vacuolar ATPase (v-ATPase) as regulators of ataxin-2 levels. We demonstrate that Etidronate--a U.S. Food and Drug Administration (FDA)-approved drug that inhibits the v-ATPase--lowers ataxin-2 protein levels in mouse and human neurons. Moreover, oral administration of the drug to mice in their water supply and food is sufficient to lower ataxin-2 levels in the brain. Thus, we uncover Etidronate as a safe and inexpensive compound for lowering ataxin-2 levels and demonstrate the utility of FACS-based screens for identifying targets to modulate levels of human disease proteins.

neuroscience↗

bioRxiv2021

The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity

BackgroundAnopheles stephensi is the most menacing malaria vector to watch for in newly urbanizing parts of the world. The fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions of malaria vectors are implicated in adaptation. ResultsWe report the assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome completes the trilogy with respect to a 16 Mbp inversion (2Rb) in An. stephensi associated with adaptation to environmental heterogeneity. Comparative genome analysis revealed breakpoint structure and allowed extraction of 22,650 segregating SNPs for typing this inversion. Using whole genome sequencing of 82 individual mosquitoes, we conclude that one third of both wild and laboratory populations maintain heterozygous genotype of 2Rb. The large number of SNPs are tailored to assign inversion genotype directly from 1740 exonic SNPs 80% of which are expressed in various developmental stages. ConclusionsThe genome trilogy approach accelerates study of fine structure and typing of important inversions in malaria vectors putting the genome resources for the much understudied An. stephensi, on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse populations cluster with IndCh pointing to significant commerce between cities, perhaps, allowing for survival of the fittest strain.

genomics↗

bioRxiv2020

Heterogenous adhesion of follower cells affects tension profile and velocity of leader cells in primary keratocyte collective cell migration

Single cell studies demonstrate membrane tension to be a central regulator of lamellipodia-driven motility bringing in front-coherence. During collective cell migration, however, tension mapping or existence of intracellular tension-gradients and the effect of cell-cell interactions have remained unexplored. In this study of membrane fluctuations and fluctuation-tension of migrating primary keratocyte cell-sheets, we first show that some leader cells are followed by followers which remain de-adhered from the substrate while being attached to other cells and thus appear to be "taking a ride". A subtle yet significant enhanced long-timescale velocity in these leaders indicate increased directionality. Intriguingly, such leaders mostly have front-high tension gradients like single keratocytes, while followers and other leaders usually display front-low membrane tension gradients. The front-high tension gradient and higher membrane tension observed in these leaders, despite the high cell-to-cell variability in membrane tension demonstrate how leader-follower interactions and heterogenous adhesion profiles are key in collective cell migration.

biophysics↗

bioRxiv2020

Behavioral and genomic sensory adaptations underlying the pest activity of Drosophila suzukii

Studying how novel phenotypes originate and evolve is fundamental to the field of evolutionary biology as it allows us to understand how organismal diversity is generated and maintained. However, determining the basis of novel phenotypes is challenging as it involves orchestrated changes at multiple biological levels. Here, we aim to overcome this challenge by using a comparative species framework combining behavioral, gene expression, and genomic analyses to understand the evolutionary novel egg-laying substrate-choice behavior of the invasive pest species Drosophila suzukii. First, we used egg-laying behavioral assays to understand the evolution of ripe fruit oviposition preference in D. suzukii as compared to closely related species D. subpulchrella and D. biarmipes, as well as D. melanogaster. We show that D. subpulchrella and D. biarmipes lay eggs on both ripe and rotten fruits, suggesting that the transition to ripe fruit preference was gradual. Secondly, using two-choice oviposition assays, we studied how D. suzukii, D. subpulchrella, D. biarmipes and D. melanogaster differentially process key sensory cues distinguishing ripe from rotten fruit during egg-laying. We found that D. suzukiis preference for ripe fruit is in part mediated through a species-specific preference for stiff substrates. Lastly, we sequenced and annotated a high-quality genome for D. subpulchrella. Using comparative genomic approaches, we identified candidate genes involved in D. suzukiis ability to seek out and target ripe fruits. Our results provide detail to the stepwise evolution of pest activity in D. suzukii, indicating important cues used by this species when finding a host, and the molecular mechanisms potentially underlying their adaptation to a new ecological niche.

evolutionary biology↗

bioRxiv2020

Predicting Chemical Shifts with Graph Neural Networks

AO_SCPLOWBSTRACTC_SCPLOWInferring molecular structure from NMR measurements requires an accurate forward model that can predict chemical shifts from 3D structure. Current forward models are limited to specific molecules like proteins and state of the art models are not differentiable. Thus they cannot be used with gradient methods like biased molecular dynamics. Here we use graph neural networks (GNNs) for NMR chemical shift prediction. Our GNN can model chemical shifts accurately and capture important phenomena like hydrogen bonding induced downfield shift between multiple proteins, secondary structure effects, and predict shifts of organic molecules. Previous empirical NMR models of protein NMR have relied on careful feature engineering with domain expertise. These GNNs are trained from data alone with no feature engineering yet are as accurate and can work on arbitrary molecular structures. The models are also efficient, able to compute one million chemical shifts in about 5 seconds. This work enables a new category of NMR models that have multiple interacting types of macromolecules.

biophysics↗

bioRxiv2020

Hidden features of the malaria vectormosquito, Anopheles stephensi ,revealed by a high-quality referencegenome

BackgroundThe mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vectors genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution. ResultsTo access previously intractable genomic regions, we generated a reference-grade genome assembly and full transcript annotations that achieve a new standard for reference genomes of disease vectors. Here, we report novel species-specific transposable element families and insertions in functional genetic elements, demonstrating the widespread role of TEs in genome evolution and phenotypic variation. We discovered 29 previously hidden members of insecticide resistance genes, uncovering new candidate genetic elements for the widespread insecticide resistance observed in An. stephensi. We identified 2.4 Mb of the Y-chromosome and seven new male-linked gene candidates, representing the most extensive coverage of the Y-chromosome in any mosquito. By tracking full length mRNA for >15 days following blood feeding, we discover distinct roles of previously uncharacterized genes in blood metabolism and female reproduction. The Y-linked heterochromatin landscape reveals extensive accumulation of long-terminal repeat retrotransposons throughout the evolution and degeneration of this chromosome. Finally, we identify a novel Y-linked putative transcription factor that is expressed constitutively through male development and adulthood, suggesting an important role throughout male development. ConclusionCollectively, these results and resources underscore the significance of previously hidden genomic elements in the biology of malaria mosquitoes and will accelerate development of genetic control strategies of malaria transmission.

genomics↗