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Hilton, A.

Publications and source records attributed to Hilton, A..

2 recordsLinked to original sources

Leveraging species-wide variation and patterns of adaptation to inform pecan crop improvement efforts

The genetic basis of adaptation is a fundamental question in evolutionary biology, and understanding how species will be able to adapt to changing conditions across their range has important implications for conservation and agriculture. To accurately interrogate the genetics of adaptation and assess the adaptive capacity of a species requires also characterizing the ways other mechanisms, including geographic distance and population dynamics, shape genetic variation. Pecan is an ecologically, culturally, and economically important North American tree, and a broader understanding of the genetics of environment adaptation will aid pecan conservation, breeding, and commercial management. Here, we use an expansive set of more than 700 pecan genotypes in combination with the first haplotype-resolved genome assembly for pecan to assess species-wide genetic variation and evaluate environmental adaptation across the native distribution. We identify five gene pools in pecan, with the lowest diversity in southern gene pools, and present evidence that gene pools began differentiating during multiple glacial cycles. Using complementary genotype-environment association approaches, we infer species-wide patterns of environmental adaptation. With these results, we predict mismatches in adaptation for pecan genotypes to different environments, including future environment scenarios. We see that in all locations, present-day genotypes incur some level of predicted maladaptation to simulated future environments, but current genetic diversity may provide a valuable source of resilience to future conditions through assisted migration. These results expand the understanding of environmental adaptation in pecan and provide insight into how long-lived species will be able to adapt to future conditions.

evolutionary biology↗

Missense mutations in the MLKL brace region lead to lethal neonatal inflammation in mice and are present in high frequency in humans.

We have isolated a mouse strain with a single missense mutation in the gene encoding MLKL, the essential effector of necroptotic cell death. The resulting substitution lies within the two-helix brace and confers constitutive, RIPK3 independent, killing activity to MLKL. Mice homozygous for MlklD139V develop lethal inflammation within days of birth, implicating the salivary glands and pericardium as hotspots for necroptosis and inflammatory infiltration. The normal development of MlklD139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, CRMO.

cell biology↗