Biology subjects

Murali, S. C.

Publications and source records attributed to Murali, S. C..

8 recordsLinked to original sources

bioRxiv2020

The structure, function, and evolution of a complete human chromosome 8

The complete assembly of each human chromosome is essential for understanding human biology and evolution. Using complementary long-read sequencing technologies, we complete the first linear assembly of a human autosome, chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08 Mbp centromeric -satellite array, a 644 kbp defensin copy number polymorphism important for disease risk, and an 863 kbp variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere. We show that the centromeric -satellite array is generally methylated except for a 73 kbp hypomethylated region of diverse higher-order -satellite enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. Using a dual long-read sequencing approach, we complete the assembly of the orthologous chromosome 8 centromeric regions in chimpanzee, orangutan, and macaque for the first time to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order -satellite structure evolved specifically in the great ape ancestor, and the centromeric region evolved with a layered symmetry, with more ancient higher-order repeats located at the periphery adjacent to monomeric -satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated at least 2.2-fold, and this acceleration extends beyond the higher-order -satellite into the flanking sequence.

genomics↗

bioRxiv2020

Genome-enabled insights into the biology of thrips as crop pests

BackgroundThe western flower thrips, Frankliniella occidentalis (Pergande), is a globally invasive pest and plant virus vector on a wide array of food, fiber and ornamental crops. While there are numerous studies centered on thrips pest and vector biology, feeding behaviors, ecology, and insecticide resistance, the underlying genetic mechanisms of the processes governing these areas of research are largely unknown. To address this gap, we present the F. occidentalis draft genome assembly and official gene set. ResultsWe report on the first genome sequence for any member of the insect order Thysanoptera. Benchmarking Universal Single-Copy Ortholog (BUSCO) assessments of the genome assembly (size = 415.8 Mb, scaffold N50 = 948.9 Kb) revealed a relatively complete and well-annotated assembly in comparison to other insect genomes. The genome is unusually GC-rich (50%) compared to other insect genomes to date. The official gene set (OGS v1.0) contains 16,859 genes, of which [~]10% were manually verified and corrected by our consortium. We focused on manual annotation, phylogenetic and expression evidence analyses for gene sets centered on primary themes in the life histories and activities of plant-colonizing insects. Highlights include: 1) divergent clades and large expansions in genes associated with environmental sensing (chemosensory receptors) and detoxification (CYP4, CYP6 and CCE enzymes) of substances encountered in agricultural environments; 2) a comprehensive set of salivary gland-associated genes supported by enriched expression; 3) apparent absence of members of the IMD innate immune defense pathway; and 4) developmental- and sex-specific expression analyses of genes associated with progression from larvae to adulthood through neometaboly, a distinct form of maturation compared to complete metamorphosis in the Holometabola. ConclusionsAnalysis of the F. occidentalis genome offers insights into the polyphagous behavior of this insect pest to find, colonize and survive on a widely diverse array of plants. The genomic resources presented here enable a more complete analysis of insect evolution and biology, providing a missing taxon for contemporary insect genomics-based analyses. Our study also offers a genomic benchmark for molecular and evolutionary investigations of other thysanopteran species.

genomics↗

bioRxiv2020

Recent ultra-rare inherited mutations identify novel autism candidate risk genes

Autism is a highly heritable, complex disorder where de novo mutation (DNM) variation contributes significantly to disease risk. Using whole-genome sequencing data from 3,474 families, we investigate another source of large-effect risk variation, ultra-rare mutations. We report and replicate a transmission disequilibrium of private likely-gene disruptive (LGD) mutations in probands but find that 95% of this burden resides outside of known DNM-enriched genes. This variant class more strongly affects multiplex family probands and supports a multi-hit model for autism. Candidate genes with private LGD variants preferentially transmitted to probands converge on the E3 ubiquitin-protein ligase complex, intracellular transport, and Erb signaling protein networks. We estimate these mutations are ~2.5 generations old and significantly younger than other mutations of similar type and frequency in siblings. Overall, private LGD variants are under strong purifying selection and act on a distinct set of genes not yet associated with autism. One sentence summaryUltra-rare autism variants preferentially transmitted to probands are younger and identify distinct gene candidates and functional networks.

genetics↗

bioRxiv2018

The Genomic Basis of Arthropod Diversity

BackgroundArthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.\n\nResultsUsing 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality and chemoperception.\n\nConclusionsThese analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.

genomics↗

bioRxiv2018

The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water

The semi-aquatic bugs conquered water surfaces worldwide and occupy ponds, streams, lakes, mangroves, and even open oceans. As such, they inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders thorough investigations of the mechanisms underlying the processes of adaptation and diversification in this group. Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome, the first water strider genome to be sequenced so far. G. buenoi genome is about 1 000Mb and the sequencing effort recovered 20 949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to water surface lifestyle. These expansions affect key processes such as growth, vision, desiccation resistance, detoxification, olfaction and epigenetic components. Strikingly, the G. buenoi genome contains three Insulin Receptors, a unique case among metazoans, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes include wavelength sensitivity shifts in opsin proteins likely in association with the requirements of vision in water habitats. Our findings suggest that local gene duplications might have had an important role during the evolution of water striders. These findings along with the G. buenoi genome open exciting research opportunities to understand adaptation and genome evolution of this unique hemimetabolous insect.

genomics↗

bioRxiv2017

Molecular evolutionary trends and feeding ecology diversification in the Hemiptera, anchored by the milkweed bug genome

BackgroundThe Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of hemipteran pests such as phloem-feeding aphids and blood-feeding bed bugs, we present the genome sequence and comparative analyses centered on the milkweed bug Oncopeltus fasciatus, a seed feeder of the family Lygaeidae.\n\nResultsThe 926-Mb Oncopeltus genome is well represented by the current assembly and official gene set. We use our genomic and RNA-seq data not only to characterize the protein-coding gene repertoire and perform isoform-specific RNAi, but also to elucidate patterns of molecular evolution and physiology. We find ongoing, lineage-specific expansion and diversification of repressive C2H2 zinc finger proteins. The discovery of intron gain and turnover specific to the Hemiptera also prompted evaluation of lineage and genome size as predictors of gene structure evolution. Furthermore, we identify enzymatic gains and losses that correlate with feeding biology, particularly for reductions associated with derived, fluid-nutrition feeding.\n\nConclusionsWith the milkweed bug, we now have a critical mass of sequenced species for a hemimetabolous insect order and close outgroup to the Holometabola, substantially improving the diversity of insect genomics. We thereby define commonalities among the Hemiptera and delve into how hemipteran genomes reflect distinct feeding ecologies. Given Oncopeltus's strength as an experimental model, these new sequence resources bolster the foundation for molecular research and highlight technical considerations for the analysis of medium-sized invertebrate genomes.

genomics↗

bioRxiv2017

Hemimetabolous genomes reveal molecular basis of termite eusociality

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the first, 2GB genome of a cockroach, Blattella germanica, and the 1.3GB genome of the drywood termite, Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.

evolutionary biology↗

bioRxiv2017

The house spider genome reveals an ancient whole-genome duplication during arachnid evolution

The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum. We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs in P. tepidariorum suggests that many have been subject to neofunctionalization and/or subfunctionalization since their duplication, and therefore may have contributed to the diversification of spiders and other pulmonate arachnids.

genomics↗