Biology subjects

Mickalide, H.

Publications and source records attributed to Mickalide, H..

4 recordsLinked to original sources

bioRxiv2023

A pan-MHC reference graph with 246 fully contiguous phased sequences

The major histocompatibility complex (MHC) is a region of the human genome that is key to immune system function but sometimes refractory to genomic analyses due to extreme polymorphism and structural variation. We performed targeted long-read sequencing and de novo assembly of MHC to create 246 highly accurate, fully contiguous, and phased full-length sequences, mostly from data provided by the Human Pangenome Reference Consortium (HPRC). We identified alleles at high resolution across 39 loci including the class I and II HLA (human leukocyte antigen) genes, discovering 1,246 putative novel allele sequences. We identified copy number variation in the C4A and C4B genes and found significant linkage disequilibrium between C4A[~]C4B haplotypes and 14 MHC loci. We build our sequences into a novel "pan-MHC" reference graph, and we demonstrate that this improves the accuracy of short-read variant calling. Our haplotypes and graph contain significantly more population diversity than preexisting MHC sequences, thus improving the prospects for global health equity in this clinically important genomic region.

genomics↗

bioRxiv2020

Closed microbial communities self-organize to persistently cycle carbon

Nutrient cycling is an emergent property of ecosystems at all scales, from microbial communities to the entire biosphere. Understanding how nutrient cycles emerge from the collective metabolism of ecosystems is a challenging problem. Here we use closed microbial ecosystems (CES), hermetically sealed consortia that sustain nutrient cycles when provided with only light, to learn how microbial communities cycle carbon. A new technique for quantifying carbon exchange shows that CES comprised of an alga and diverse bacteria self-organize to robustly cycle carbon. Comparing a library of CES, we find that carbon cycling does not depend strongly on the taxonomy of the bacteria present. Metabolic profiling reveals functional redundancy across CES: despite strong taxonomic differences, self-organized CES exhibit a conserved set of metabolic capabilities. SummaryClosed microbial communities of algae and bacteria self-organize to robustly cycle carbon via emergent metabolite exchange.

ecology↗

bioRxiv2019

Higher-order interaction inhibits bacterial invasion of a phototroph-predator microbial community

In nature, the composition of an ecosystem is thought to be important for determining its resistance to invasion by new species. Studies of invasions in natural ecosystems, from plant to microbial communities, have found that more diverse communities are more resistant to invasion. It is thought that more diverse communities resist invasion by more completely consuming the resources necessary for would-be invaders. Here we show that Escherichia coli can successfully invade cultures of the alga Chlamydomonas reinhardtii (phototroph) or the ciliate Tetrahymena thermophila (predator), but cannot invade a community where both are present. The invasion resistance of the algae-ciliate community is due to a higher-order (3-way) interaction that is unrelated to resource consumption. We show that the mechanism of this interaction is the algal inhibition of bacterial aggregation which leaves bacteria vulnerable to ciliate predation. This mechanism of invasion resistance requires both the algae and the ciliate to be present and provides an example of invasion resistance through a trait-mediated higher-order interaction.

ecology↗

bioRxiv2016

Environment determines evolutionary trajectory in a constrained phenotypic space

Constraints on phenotypic variation limit the capacity of organisms to adapt to the multiple selection pressures encountered in natural environments. To better understand evolutionary dynamics in this context, we select Escherichia coli for faster migration through a porous environment, a process which depends on both motility and growth. We find that a trade-off between swimming speed and growth rate constrains the evolution of faster migration. Evolving faster migration in rich medium results in slow growth and fast swimming, while evolution in minimal medium results in fast growth and slow swimming. In each condition parallel genomic evolution drives adaptation through different mutations. We show that the trade-off is mediated by antagonistic pleiotropy through mutations that affect negative regulation. A model of the evolutionary process shows that the genetic capacity of an organism to vary traits can qualitatively alter the evolutionary trajectory when selection pressures are complex.

evolutionary biology↗