Biology subjects

Chamala, S.

Publications and source records attributed to Chamala, S..

3 recordsLinked to original sources

bioRxiv2022

Development and application of a computable genotype model in the GA4GH Variation Representation Specification

As the diversity of genomic variation data increases with our growing understanding of the role of variation in health and disease, it is critical to develop standards for precise inter-system exchange of these data for research and clinical applications. The Global Alliance for Genomics and Health (GA4GH) Variation Representation Specification (VRS) meets this need through a technical terminology and information model for disambiguating and concisely representing variation concepts. Here we discuss the recent Genotype model in VRS, which may be used to represent the allelic composition of a genetic locus. We demonstrate the use of the Genotype model and the constituent Haplotype model for the precise and interoperable representation of pharmacogenomic diplotypes, HGVS variants, and VCF records using VRS and discuss how this can be leveraged to enable interoperable exchange and search operations between assayed variation and genomic knowledgebases.

bioinformatics↗

bioRxiv2020

Natural selection imposed by mechanical properties of a biomaterial results in novel cellular phenotypes

Mechanical properties such as substrate stiffness are a ubiquitous feature of a cells environment. Many types of animal cells exhibit canonical phenotypic plasticity when grown on substrates of differing stiffness, in vitro and in vivo. Whether such plasticity is a multivariate optimum due to hundreds of millions of years of animal evolution, or instead is a compromise between conflicting selective demands, is unknown. We addressed these questions by means of experimental evolution of populations of mouse fibroblasts propagated for ~90 cell generations on soft or stiff substrates. The ancestral cells grow twice as fast on stiff substrate as on soft substrate and exhibit the canonical phenotypic plasticity. Soft-selected lines derived from a genetically diverse ancestral population increased growth rate on soft substrate to the ancestral level on stiff substrate and evolved the same multivariate phenotype. The pattern of plasticity in the soft-selected lines was opposite of the ancestral pattern, suggesting that reverse plasticity underlies the observed rapid evolution. Conversely, growth rate and phenotypes did not change in selected lines derived from clonal cells. Overall, our results suggest that the changes were the result of genetic evolution and not phenotypic plasticity per se. Whole-transcriptome analysis revealed consistent differentiation between ancestral and soft-selected populations, and that both emergent phenotypes and gene expression tended to revert in the soft-selected lines. However, the selected populations appear to have achieved the same phenotypic outcome by means of at least two distinct transcriptional architectures related to mechano-transduction and proliferation.

evolutionary biology↗

bioRxiv2019

The Avocado Genome Informs Deep Angiosperm Phylogeny, Highlights Introgressive Hybridization, and Reveals Pathogen Influenced Gene Space Adaptation

The avocado, Persea americana, is a fruit crop of immense importance to Mexican agriculture with an increasing demand worldwide. Avocado lies in the anciently-diverged magnoliid clade of angiosperms, which has a controversial phylogenetic position relative to eudicots and monocots. We sequenced the nuclear genomes of the Mexican avocado race, P. americana var. drymifolia, and the most commercially popular hybrid cultivar, Hass, and anchored the latter to chromosomes using a genetic map. Resequencing of Guatemalan and West Indian varieties revealed that [~]39% of the Hass genome represents Guatemalan source regions introgressed into a Mexican race background. Some introgressed blocks are extremely large, consistent with the recent origin of the cultivar. The avocado lineage experienced two lineage-specific polyploidy events during its evolutionary history. Although gene-tree/species-tree phylogenomic results are inconclusive, syntenic ortholog distances to other species place avocado as sister to the enormous monocot and eudicot lineages combined. Duplicate genes descending from polyploidy augmented the transcription factor diversity of avocado, while tandem duplicates enhanced the secondary metabolism of the species. Phenylpropanoid biosynthesis, known to be elicited by Colletotrichum (anthracnose) pathogen infection in avocado, is one enriched function among tandems. Furthermore, transcriptome data show that tandem duplicates are significantly up- and down-regulated in response to anthracnose infection, whereas polyploid duplicates are not, supporting the general view that collections of tandem duplicates contribute evolutionarily recent \"tuning knobs\" in the genome adaptive landscapes of given species.\n\nSIGNIFICANCE STATEMENTAvocado is a nutritious, economically important fruit species that occupies an unresolved position near the earliest evolutionary branchings of flowering plants. Our nuclear genome sequences of Mexican and Hass variety avocados inform ancient evolutionary relationships and genome doublings, the admixed nature of Hass, and provide a look at how pathogen interactions have shaped avocados more recent genomic evolutionary history.

genomics↗