da Fonseca, R. | bioRxiv Science

bioRxiv2025

Ghrelin and Mboat4 are lost in Serpentes

Exploring the evolution of gene networks associated with metabolic/energetic homeostasis can yield key insights into the adaptive landscapes governing the physioology of extant lineages. Here, we investigate a key hormonal module of energy metabolism in reptiles. Ghrelin (GHRL), also known as the "hunger hormone", is a multifunctional gastric peptide, involved in appetite, food intake and body weight regulation. We examined the genomes of 112 species comprising members of the Squamata, Testudines, Crocodilia and Rhynchocephalia and provide ample evidence that GHRL was independently lost in snakes, chameleons and toadhead agamas. In accordance, the enzyme responsible for ghrelin acylation and essential for its activity (membrane bound O-acyltransferase domain containing 4), is also eroded in these lineages. We suggest that the loss of this hormonal signalling system parallels critical modifications in energy metabolism, including a lower need to stimulate fatty acid oxidation during fasting in the locomotor muscles of snakes compared to other groups.

evolutionary biology↗

bioRxiv2025

PseudoChecker2 and PseudoViz: automation and visualization of gene loss in the Genome Era

High-fidelity genome assemblies provide unprecedented opportunities to decipher mechanisms of molecular evolution and phenotype landscapes. Here, we present PseudoChecker2, a command-line version of the web-tool PseudoChecker with expanded functions. It identifies gene loss via drastic mutational events such as premature stop codons, deletions and insertions. It enables the investigation of cross-species genomic datasets through: (i) integration into automated workflows, (ii) multiprocessing capability, and (iii) creation of a functional reference from annotation files. In addition, we introduce PseudoViz, a novel graphical interface designed to help interpret the results of PseudoChecker2 with intuitive visualizations. These tools combine the versatility and automation of a command-line tool with the user-friendliness of a graphical interface to tackle the challenges of the Genome Era. Availability and implementationPseudoChecker2 and PseudoViz are fully available at https://github.com/rresendepinto/PseudoChecker2 and https://github.com/rresendepinto/PseudoViz.

bioinformatics↗

bioRxiv2019

Link Your Sites (LYS) Scripts: Automated search of protein structures and mapping of sites under positive selection detected by PAML

The visualization of the molecular context of an amino acid mutation in a protein structure is crucial for the assessment of its functional impact and to understand its evolutionary implications. Currently, searches for fast evolving amino acid positions using codon substitution models like those implemented in PAML [1] are done in almost complete proteomes, generating large numbers of candidate proteins that require individual structural analyses. Here we present two python wrapper scripts as the package Link Your Sites (LYS). The first one i) mines the RCSB database [10] using the blast alignment tool to find the best matching homologous sequences, ii) fetches their domain positions by using Prosites [3,8,9], iii) parses the output of PAML extracting the positional information of fast-evolving sites and transform them into the coordinate system of the protein structure, iv) outputs a file per gene with the positions correlations to its homologous sequence. The second script uses the output of the first one to generate the proteins graphical assessment. LYS can therefore generate figures to be used in publication highlighting the positively selected sites mapped on regions that are known to have functional relevance and/or be used to reduce the number of targets that will be further analyzed by providing a list of those for which structural information can be retrieved. MotivationAutomatizing the search for protein structures to assess the functional impact of sites found to be under positive selection by codeml, implemented in PAML [1]. Building publication-quality figures highlighting the sites on a protein structure model that are within and outside functional domains. reduces the workload associated with selecting proteins for which a functional assessment of the impact of mutations can be done using a protein structure. This is especially relevant when analyzing almost complete proteomes which is the case of large comparative genomic studies. SoftwareLYS scripts are executed in the command line. They automatically search for homologous proteins at the RSCB database [10], determine the functional domain locations and correlate the positions pointed by the M8 model [1], and output a data frame that can be used as the input by PyMOL [7] to generate a visualization of the results. AvailabilityLYS is easy to install and implement and they are available at https://github.com/LysSanzMoreta/LYSAutomaticSearch

bioinformatics↗