Oxygen-sensing regulatory architecture structures mammalian diversification
July 24, 2026·
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Jeroen B. Smaers
Alejandro Gil Gómez
Rosalind E. M. Rickaby
Christopher W. Pugh
C. West
P. Aggarwal
A. Hecker
A. Chen
C. Wen
Markus Riessland
Joshua S Rest
Abstract
The HIF oxygen-sensing pathway traces to the last metazoan common ancestor ~800 million years ago and is conventionally viewed as a conserved cellular stress-response module. We analyzed sequence-encoded TF-gene regulatory architecture for 34 transcription factors and 705 genes in 10 oxygen-sensing pathways across 239 mammalian species. Oxygen-sensing regulatory architecture carries strong clade-structured evolutionary signal, tracking placental evolution, atmospheric O2, life history, ecological specializations and cancer resistance. Major radiations occupy discrete, heritable configurations established at key phylogenetic transitions and retained across descendant lineages, revealing regulatory architecture lock-in as a structuring force in macroevolution.
Type
Publication
bioRxiv (preprint)
Authors
Computational Scientist
Alejandro Gil Gómez, Ph.D., is a Computational Scientist at Stony Brook Medicine and Research Computing focused on clinical and translational research. His expertise spans end-to-end bioinformatics, AI/ML workflows, and high-performance computing (HPC). He specializes in developing scalable, reproducible pipelines for a wide array of data types, including RNA-seq differential expression, genomic variant analysis, proteomics, and spatial omics. Experienced in processing HIPAA-regulated clinical datasets, he bridges advanced computational workflows with practical biomedical discovery. He holds a Ph.D. in Ecology and Evolution from Stony Brook University and has also taught bioinformatics and mentored students in data-intensive research.