Biology subjects

Wilson, D. B.

Publications and source records attributed to Wilson, D. B..

3 recordsLinked to original sources

bioRxiv2021

Genetic diversity in facultatively sexual populations and its implications for the origins of self-incompatibility in algae and fungi

The evolutionary mechanism that drove the establishment of self-incompatibility in early sexual eukaryotes is still a debated topic. While a number of competing hypotheses have been proposed, many have not received detailed theoretical attention. In particular, the hypothesis that self-incompatibility increases the benefits of genetic recombination in sexual haploids has been comparatively understudied. In this paper we address this topic by mathematically deriving how the probability of mating with a genetically distinct individual changes as a function of the presence or absence of self-incompatible mating type classes. We find that although populations with mating types successfully engage in sexual reproduction less frequently than their self-compatible competitors, they can nevertheless engage in useful sex with genetically distinct partners more frequently. This conclusion holds when the number of sexual reproductive events per generation is low (i.e. in small populations with low rates of facultative sexual reproduction). Finally we demonstrate the potential for frequency-dependent selection in competitive dynamics between self-compatible and self-incompatible types. These analytic results provide a baseline for studying the sex advantage enhancer model for the evolutionary origin of mating types within each specific hypothesis for the evolution of recombination. PACS87.23.-n Ecology and evolution, 87.23.Kg Dynamics of evolution, 02.50.Ey Stochastic processes 2000 MSC37N25: Dynamical systems in biology, 60J70: Applications of diffusion theory (population genetics, absorption problems, etc.)

evolutionary biology↗

bioRxiv2020

The discriminatory power of the T cell receptor

T cells use their T-cell receptors (TCRs) to discriminate between lower-affinity self and higher affinity non-self pMHC antigens. Although the discriminatory power of the TCR is widely believed to be near-perfect, technical difficulties have hampered efforts to precisely quantify it. Here, we describe a method for measuring very low TCR/pMHC affinities, and use it to measure the discriminatory power of the TCR, and the factors affecting it. We find that TCR discrimination, although enhanced compared with conventional cell-surface receptors, is imperfect: primary human T cells can respond to pMHC with affinities as low as KD ~1 mM. The kinetic proofreading mechanism fit our data, providing the first estimates of both the time delay (2.8 s) and number of biochemical steps (2.67) that are consistent with the extraordinary sensitivity of antigen recognition. Our findings explain why self pMHC frequently induce autoimmune diseases and anti-tumour responses, and suggest ways to modify TCR discrimination.

immunology↗

bioRxiv2020

T cells exhibit unexpectedly low discriminatory power and can respond to ultra-low affinity peptide-MHC ligands

T cells use their T cell receptors (TCRs) to discriminate between peptide MHC (pMHC) ligands that bind with different affinities but precisely how different remains controversial. This is partly because the affinities of physiologically relevant interactions are often too weak to measure. Here, we introduce a surface plasmon resonance protocol to measure ultra-low TCR/pMHC affinities (KD ~ 1000 M). Using naive, memory, and blasted human CD8+ T cells we find that their discrimination power is unexpectedly low, in that they require a large >100-fold decrease in affinity to abolish responses. Interestingly, the discrimination power reduces further when antigen is presented in isolation on artificial surfaces but can be partially restored by adding ligands to CD2 or LFA-1. We were able to fit the kinetic proof-reading model to our data, yielding the first estimates for both the time delay (2.8 s) and number of biochemical steps (2.67). The fractional number of steps suggest that one of the proof-reading steps is not easily reversible.

immunology↗