Biology subjects

Palmer, M. E.

Publications and source records attributed to Palmer, M. E..

3 recordsLinked to original sources

bioRxiv2026

Advances in the Design and Functionality of a Compact Multi-Reflecting Time-of-Flight Mass Spectrometer

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSRationaleC_ST_ABSHigh-resolution mass spectrometry is routinely used for the analysis of complex samples in pharmaceutical, environmental, and omics related studies. Such applications demand instrumentation to be capable of combining sub-ppm mass accuracy, high resolving power, rapid full m/z range acquisition, over a wide dynamic range. MethodsAchieving the above requirements places constraints on analyzer design and performance. Multi-reflecting time-of-flight (MRT) based analyzers have previously been reported as a means of significantly extending the effective flight path in compact TOF designs. Here, further instrument and functionality advances in a compact MRT mass spectrometer design are described. ResultsThe impact of these enhancements was assessed for targeted and non-targeted omics applications, examining the impact of acquisition speed on resolving power, dynamic range including limits of quantitation, and quantitative precision. ConclusionThe results obtained characterize the performance of the enhanced design features of a compact MRT mass spectrometer. Operation at elevated acquisition rates up to 200 Hz was observed without loss in resolving power, isotopic ratio accuracy, or quantitative precision.

biochemistry↗

bioRxiv2026

Adaptive loss of function accelerated the evolution of ancient and modern human cognition

Methods to detect accelerated evolution have identified many genomic regions with unexpectedly rapid evolution in the human lineage-significantly more than in chimpanzees, our closest living relatives. However, these methods focus on accelerated sequence evolution of short non-coding regions, leaving open the questions of how to identify accelerated evolution of molecular function, as opposed to sequence, and whether accelerated evolution has shaped the human genome more broadly. Here, we introduce a new approach to detect accelerated evolution: Function Aware Statistical Test for Evolutionary Rates (FASTER). In contrast to previous methods, FASTER can detect not only accelerated evolution of sequence, but also of predicted function, and can be applied to any set of genomic regions. Applying this method to humans and chimpanzees, we identified protein-coding, untranslated (UTR), and non-coding regions with accelerated evolution of function. Across all these genomic levels, we consistently found more rapid evolution in conserved sites in the human lineage compared to chimpanzee, many of which are predicted to reduce protein stability or chromatin accessibility. Multiple lines of evidence suggest this human-acceleration was driven in part by positive selection on brain development and cognition which has continued to shape human evolution even in the past several thousand years. Collectively, these results demonstrate the power of genome-wide scans for the evolution of predicted function and specifically suggest that a higher rate of reduction in function-including widespread decreases in cis-regulatory activity-may have been an important driver of both ancient and recent human evolution.

genomics↗

bioRxiv2025

A framework to detect positive selection using variant effect predictions reveals widespread adaptive evolution of human neurons

Detecting positive selection is essential to understanding evolution. Many methods to detect positive selection use simple classifications of genetic variants (e.g. synonymous/nonsynonymous). Here, we propose that these methods can be considered special cases of a more general framework to detect positive selection with any variant effect prediction method. Using evolutionary conservation and deep learning-based variant effect predictions, we apply this framework genome-wide in the human lineage and identify positive selection on protein sequences of genes involved in brain and heart development, chromatin accessibility in binding sites of dozens of transcription factors, and non-coding substitutions in compact genomic regions with reinforcing cell type-specific effects on cis-regulatory activity. Consistently, the dominant theme was positive selection on genes regulating neuronal connectivity, suggesting that fine-scale changes in brain wiring were essential to the evolution of human cognition. Overall, this framework represents a powerful, versatile tool to investigate adaptive evolution across the tree of life.

genomics↗