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Keith, N.

Publications and source records attributed to Keith, N..

2 recordsLinked to original sources

Discovery and evaluation of cadmium-adapted Daphnia pulex genotypes in a region of historical mining reveals adaptation protects the germline from cadmium-induced mutations

Exposure to chemical pollutants can alter the rate, and genome-wide distribution of germline mutations. However, studies measuring the effect of chemical exposure on mutation rate and spectra have not considered the ecological and evolutionary backgrounds of studied genotypes, which could influence the rates and patterns of germline mutations in altered environments, e.g., chemical pollution. Utilizing a study of natural Daphnia pulex populations, we conducted a comprehensive experiment to test our hypothesis that adaptation to chemical pollution also protects the germline from mutagenesis. We, 1) identified Daphnia pulex populations that have adapted to live in mining-devastated regions by increasing their cadmium tolerance. 2) We completed a mutation-accumulation (MA) experiment with an adapted genotype to measure the germline mutation rate in both control conditions and an environmentally relevant cadmium concentration. 3) We compared these MA experiment results to a previously reported, identically designed MA experiment with a nonadapted genotype. We report that patterns of cadmium-induced mutagenesis in the adapted genotype were reversed compared to our previous observations in the nonadapted genotype. Cadmium exposure altered the single nucleotide mutation (SNM) rate in the same genome regions in adapted and nonadapted genotypes, but the rates were changed in opposite directions. Cadmium also altered specific SNM classes in these genotypes in opposite directions. The reversal of mutational trends in the adapted genotype suggests protection against cadmium genotoxicity. We further demonstrate that adapted populations have elevated gene copy-number and expression levels of metallothionein, the protein that protects against cadmium toxicity by binding to cadmium irreversibly.

evolutionary biology↗

Molecular and functional characterization of the Drosophila melanogaster conserved smORFome

Short polypeptides encoded by small open reading frames (smORFs) are ubiquitously found in eukaryotic genomes and are important regulators of physiology, development, and mitochondrial processes. Here, we focus on a subset of 298 smORFs that are evolutionarily conserved between Drosophila melanogaster and humans. Many of these smORFs are conserved broadly in the bilaterian lineage, with [~]182 conserved in plants. Within these conserved smORFs, we observed remarkably heterogenous spatial and temporal expression patterns - indicating wide-spread tissue-specific and stage-specific mitochondrial architectures. In addition, an analysis of annotated functional domains revealed a predicted enrichment of smORF polypeptides localizing to mitochondria. We conducted an embryonic ribosome profiling experiment finding support for translation of 137 of these smORFs during embryogenesis. We further embarked on functional characterization using CRISPR knockout/activation, RNAi knockdown, and cDNA overexpression, revealing diverse phenotypes. This study underscores the importance of identifying smORF function in disease and phenotypic diversity.

genomics↗