Biology subjects

Thakare, A.

Publications and source records attributed to Thakare, A..

3 recordsLinked to original sources

bioRxiv2024

The first assembled chromosome-level genome of an individual from Karnataka, India

We present the first chromosome-level assembled genome of an individual from Karnataka, India (KIn1), using de novo assembly of 12x coverage of PacBio HiFi reads generated in-house and 30x Hi-C data from the most ethnically related individual to KIn1 from Andhra Pradesh (HG04712), publicly available under International Genome Sample Resource (IGSR). We achieved an N50 of 137 Mb and an L50 of 9--very close to the maximum achievable N50 of 147 Mb and minimum achievable L50 of 8 respectively for human genomes. A comparison of the KIn1 assembly with assemblies of four other individual genomes from a Puerto Rican (PR1), Ashkenazi (Ash1), Hans Chinese (Hans1), and Northern European (T2T) reported to date from resources like IGSR and/or Genome-in-a-Bottle (GIBR) collections shows that the longest scaffolds from KIn1 cover 80-90% of the reference chromosomes and exhibit near collinearity. We find a unique inversion in the chromosome 7 euchromatic region and other major translocations in chromosomes 17 and 20 in KIn1. We also produced a chromosome-level assembly for another individual from Punjab, Lahore (HG03492), for use in our comparison. The analysis of variants among select IGSR individuals using the KIn1 assembly as a reference reveals that the Indian Telugu from the UK (ITU) population in IGSR is ethnically closest to KIn1, followed by the Sri Lankan Tamil from the UK (STU) as representatives of South Asian ancestry.

genomics↗

bioRxiv2022

Identification of a TNF-TNFR-like system in malaria vectors (Anopheles stephensi) likely to influence Plasmodium resistance

Identification of Plasmodium-resistance genes in malaria vectors remains an elusive goal despite the recent availability of high-quality genomes of several mosquito vectors. An. stephensi, with its three distinctly-identifiable forms at the egg stage, correlating with varying vector competence, offers an ideal species to discover functional mosquito genes implicated in Plasmodium resistance. Recently, the genomes of several strains of An. stephensi of the type-form, known to display high vectorial capacity, have been reported. Here, we report a chromosomal-level assembly of an intermediate-form of An. stephensi strain (IndInt), shown to have reduced vectorial capacity relative to a strain of type-form (IndCh). The contig level assembly with a L50 of 4 was scaffolded into chromosomes by using the genome of IndCh as the reference. The final assembly shows a heterozygous paracentric inversion, 3Li, involving 8 Mbp, which is syntenic to the extensively-studied 2La inversion implicated in Plasmodium resistance in An. gambiae involving 21 Mbp. Deep annotation of genes within the 3Li region in IndInt assembly using the state-of-the-art protein-fold prediction and other annotation tools reveals the presence of a TNF-like gene, which is the homolog of the eiger gene in Drosophila. Subsequent chromosome-wide searches revealed homologs of wengen (wgn) and grindelwald (grnd) genes in IndInt, which are known to be the receptors for eiger in Drosophila. We have identified all the genes in IndInt required for eiger-mediated signaling by analogy to TNF-TNFR system, suggesting the presence of a functionally active eiger signaling pathway present in IndInt. Comparative genomics of high-quality genome assemblies of the three type-forms with that of IndInt, reveals structurally disruptive mutations in eiger gene in all three strains of the type-form, alluding to compromised innate immunity in the type-form as the cause of high vectorial capacity in these strains. This is the first report of the presence of an intact evolutionarily-conserved TNF-TNFR signaling system in malaria vectors, with a potential role in Plasmodium resistance.

genomics↗

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↗