Biology subjects

Santana-Molina, C.

Publications and source records attributed to Santana-Molina, C..

4 recordsLinked to original sources

bioRxiv2026

Origins of eukaryotic metabolism

The origin of eukaryotes is a key event in the evolution of cellular life hypothesized to involve a symbiotic integration between a member of the Asgard archaea and the Alphaproteobacteria. Recent work has provided evidence for additional genetic input from other prokaryotes to the eukaryotic proteome yet the extent and sources of these contributions remain debated. Here we aimed to further resolve the prokaryotic origins of eukaryotic genes to inform our understanding of eukaryogenesis. Specifically, we developed a phylogenetic framework to investigate the origins of eukaryotic gene families associated with metabolism and informational processing for comparison. We found that informational processing genes were predominantly derived by archaea whereas eukaryotic metabolism is highly chimeric in its origin. In contrast to previous studies, we report a substantial number of archaeal origins of diverse metabolic enzymes including key metabolic regulators. This highlights an overlooked participation of archaeal metabolism and pinpoints potential metabolic integrations during eukaryogenesis. Apart from the alphaproteobacterial contributions to the eukaryotic metabolism, we found an additional dominant phylogenetic signal of genes potentially derived from Myxococcota, especially for gene families associated with lipid metabolism. By systematically analysing the origins of eukaryotic metabolism, this research offers novel insights into the origin of eukaryotic membranes and refine our current models for the origin of the eukaryotic cell.

evolutionary biology↗

bioRxiv2025

Domain-combination based pan-genomic Tree of Life

Reconstructing the Tree of Life (ToL) remains a central challenge in evolutionary biology. While sequence-based methods have resolved much of lifes diversity, deep evolutionary relationships often remain elusive, particularly across the three superkingdoms of life. Here, we present a complementary approach using genome-wide occurrence of protein domain combinations as phylogenetic signal. We analyzed 5,343 complete proteomes spanning Bacteria, Archaea, and Eukaryota, and inferred a pan-genomic ToL from [~]77,000 domain combinations, including isolated domains and domain pairs. Our reconstruction recovers major clades and captures both vertical inheritance and signals from non-vertical processes such as lateral gene transfer, endosymbiosis, and genome reduction. Ancestral reconstructions reveal functional innovations that mark key evolutionary transitions--such as the emergence of vesicle trafficking in Eukaryota or methanogenesis in Archaea. We found that organisms with reduced genomes, like Chlamydiota, tend to be misplaced in domain combination-based phylogenies due to sparse combinatorial data. Our results demonstrate that domain combinations carry a strong, evolutionary signal that is both biologically and functionally informative. While not a substitute for sequence-based phylogenetics, domain combination-based trees offer an alternative perspective, capable of integrating both vertical and lateral processes into a unified evolutionary framework. Author SummaryTraditional evolutionary trees are typically built from sequences, but this approach struggles to resolve deep branches in the Tree of Life. Here, we use combinations of protein domains--the functional modules that make up proteins to resolve major relationships in the tree. By analyzing over 5,000 complete proteomes from Bacteria, Archaea, and Eukaryotes, we reconstruct a Tree of Life that reflects both vertical inheritance and key evolutionary processes like endosymbiosis and gene transfer. This domain-based approach not only recovers known relationships but also reveals how major biological innovations emerged. Our results show that domain combinations provide a powerful and interpretable signal for studying evolution at a genomic scale.

evolutionary biology↗

bioRxiv2021

The 'squalene route' to carotenoid biosynthesis is widespread in Bacteria.

Squalene is mostly associated with the biosynthesis of polycyclic triterpenes. Although there have been suggestions that squalene could be involved in the biosynthesis of carotenoids, functionally and evolutionarily related to polycyclic triterpenes, evidence of this squalene route in nature was lacking. We demonstrate that planctomycetes synthesize C30 carotenoids via squalene and that this squalene route is widely distributed in Bacteria. We also investigated the functional roles of hopanoids and carotenoids in Planctomycetes and show that their protective functions under stress conditions are complementary. Our evolutionary analyses suggest that the C30 carotenoid biosynthetic pathway is the most ancestral, with a potential origin in Firmicutes or Planctomycetes. In addition, we propose an evolutionary scenario to explain the diversification of the different carotenoid and squalene pathways. Together, these results improve the evolutionary contextualization of these molecules. Likewise, the widespread occurrence of the squalene route in bacteria increases the functional repertoire of squalene.

microbiology↗

bioRxiv2020

Functional diversity of isoprenoidal lipids in Methylobacterium extorquens PA1

Hopanoids and carotenoids are two of the major isoprenoid-derived lipid classes in prokaryotes that have been proposed to have similar membrane ordering properties as sterols. Methylobacterium extorquens contains hopanoids and carotenoids in their outer membrane, making them an ideal system to investigate whether isoprenoid lipids play a complementary role in outer membrane ordering and cellular fitness. By genetically knocking out hpnE, and crtB we disrupted the production of squalene, and phytoene in Methylobacterium extorquens PA1, which are the presumed precursors for hopanoids and carotenoids, respectively. Deletion of hpnE unexpectedly revealed that carotenoid biosynthesis utilizes squalene as a precursor resulting in a pigmentation with a C30 backbone, rather than the previously predicted C40 phytoene-derived pathway. We demonstrate that hopanoids but not carotenoids are essential for growth at high temperature. However, disruption of either carotenoid or hopanoid synthesis leads to opposing effects on outer membrane lipid packing. These observations show that hopanoids and carotenoids may serve complementary biophysical roles in the outer membrane. Phylogenetic analysis suggests that M. extorquens may have acquired the C30 pathway through lateral gene transfer with Planctomycetes. This suggests that the C30 carotenoid pathway may have provided an evolutionary advantage to M. extorquens. ImportanceAll cells have a membrane that delineates the boundary between life and its environment. To function properly, membranes must maintain a delicate balance of physical and chemical properties. Lipids play a crucial role in tuning membrane properties. In eukaryotic organisms from yeast to mammals, sterols are essential for assembling a cell surface membrane that can support life. However, bacteria generally do not make sterols, so how do they solve this problem? Hopanoids and carotenoids are two major bacterial lipids, that are proposed as sterol surrogates. In this study we explore the bacterium M. extorquens for studying the role of hopanoids and carotenoids in surface membrane properties and cellular growth. Our findings suggest that hopanoids and carotenoids may serve complementary roles balancing outer membrane properties, and provide a foundation for elucidating the principles of surface membrane adaptation.

microbiology↗