The 'shape' of gene expression: Identifying genes that may share roles across species
Much of what we know about biology comes from animal models, particularly mice. Applying these insights to humans, however, is not always straightforward. For example, some of the genes important for the formation of germ cells, which eventually give rise to eggs or sperm, differ between mice and humans.
This groundbreaking research from Kyoto University's Institute for the Advanced Study of Human Biology (WPI-ASHBi) explores the shape of gene expression to identify genes that share similar roles across various species. The study, published in Cell Reports Methods, introduces a novel method called Species-OT that compares gene expression patterns to establish evolutionary relationships between genes.
By analyzing the geometric shapes formed by gene expression vectors, Species-OT can pinpoint candidate gene correspondences across different species, even when the specific genes involved may differ. The researchers focused on genes encoding transcription factors, which are expected to form the core of gene regulatory networks. To validate the method, they analyzed gene expression during the development of primordial germ cell-like cells from mouse and human pluripotent stem cells.
The results revealed promising matches between mouse and human genes that previously showed similar roles. Furthermore, the analysis showed relative similarity in the overall patterns of gene expression between humans and cynomolgus macaques, while mice were more distinct from both. The study also examined single-cell RNA-sequencing data from six mammalian species, revealing similarities among primates and among gorillas, orangutans, and cynomolgus macaques.
Importantly, mouse expression patterns differed significantly from those of the primates. These findings suggest that Species-OT can provide insights into shared gene regulatory mechanisms across species, which could be crucial for translating animal research findings to human disease understanding. The researchers hope to apply this method to other cell types, cell fate specification processes, and even differences between individuals to further refine our understanding of shared and specific mechanisms across species.
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