image: On the left, GACNEs are unevenly distributed across the genome, forming distinct hotspots. On the right, the Manhattan plots highlight these clustered regions and their associations with genes involved in the Wnt signaling pathway. At the bottom, functional enrichment analysis shows the biological functions associated with genes near GACNE hotspots.
Credit: ©Science China Press
Gliding has evolved independently six times in living mammals, making it a classic example of convergent evolution. Why does nature repeatedly produce similar complex adaptive traits? When distantly related species evolve similar features, do they rely on the same genetic changes, or can different genetic changes lead to similar outcomes?
A research team led by Academician Fuwen Wei at the Institute of Zoology, Chinese Academy of Sciences, has provided new insights into these questions. The study, published in Science China Life Sciences, found that independently evolved gliding mammals rarely share the same rapidly evolving regulatory regions. Instead, different regulatory regions may be associated with similar genes, regulatory networks, and developmental pathways, suggesting that similar biological functions can evolve through different genetic changes.
To investigate the genetic basis of gliding evolution, the researchers generated chromosome-level genomes for the red-and-white giant flying squirrel, Petaurista alborufus, and the sugar glider, Petaurus breviceps. They then compared genomes from 17 mammalian species representing three independently evolved gliding lineages.
The study focused on conserved non-coding elements, or CNEs. These are regions of the genome that have remained highly conserved during evolution and are thought to play important roles in gene regulation. The researchers identified CNEs that showed accelerated evolution specifically in gliding lineages and defined them as gliding-specific accelerated conserved non-coding elements, or GACNEs.
The locations of GACNEs were widely scattered across the genomes of the three gliding lineages, with very little overlap between lineages. This indicates that the same regulatory regions were generally not repeatedly altered during the independent evolution of gliding. The researchers then examined whether different regulatory regions could nevertheless have similar functions. Although the specific genes associated with GACNEs differed among gliding lineages, these genes showed similar patterns of functional enrichment. The associated functions included processes related to appendage development, brain development, and Wnt signaling.
The researchers also found that GACNEs were not randomly distributed across the genome. Instead, they were concentrated in multiple genomic regions, forming evolutionary hotspots. These hotspots differed in genomic location among the three gliding lineages, but the genes associated with the hotspots showed similar functional patterns. Closely related non-gliding species did not show comparable patterns. This difference provides additional support for a possible connection between the observed regulatory changes and the evolution of gliding.
By combining information on GACNE-associated genes, evolutionary hotspots, and transcription factors, the researchers identified several candidate regulators that may be involved in gliding adaptation. These included EMX2, ZFHX3, TCF7L2, TLE1, and CTBP2. Previous studies have shown that EMX2 plays an important role in wing membrane formation. The new study also identifies ZFHX3 as a candidate regulator for future investigation because it may be involved in several processes related to wing membrane development, muscle formation, cartilage development, and circadian regulation.
The researchers further compared the candidate regulatory regions with previously reported enhancers. Several candidate enhancers associated with gliding overlapped with regulatory regions known to be active in embryonic forelimb and lateral body regions. This finding provides additional support for a possible role of these regulatory regions in wing membrane development.
Together, the findings suggest that repeated evolution of gliding does not necessarily require the same regulatory regions to change repeatedly. Instead, different regulatory regions may influence similar genes and biological pathways, producing functional similarities despite differences in their DNA sequences.
The study provides a new perspective on how complex adaptive traits can evolve repeatedly. Similar phenotypes may arise not only through repeated changes in the same genes or regulatory regions, but also through different genetic changes that affect common biological functions.
The researchers note that the regulatory regions and transcription factors identified in the study are candidates for future functional studies. Further work combining genomic, epigenomic, and gene expression data, together with experimental approaches, will be needed to determine how these regulatory regions affect development and contribute to the evolution of gliding.
The findings may also provide a framework for studying other complex traits that have evolved independently in different species. Comparing genetic changes across independently evolved traits may help reveal when evolution repeatedly uses the same molecular changes and when different genetic routes can produce similar biological outcomes.
See the article:
Functional convergence of regulatory regions provides vital insights into mammalian gliding adaptation
https://doi.org/10.1007/s11427-026-3340-3
Journal
Science China Life Sciences