Biology subjects

Penna, A.

Publications and source records attributed to Penna, A..

7 recordsLinked to original sources

bioRxiv2026

Conserved covariance structure underlies 60 million years of morphological diversification in primates

Evolvability, the capacity of populations to respond to selection, is shaped by the structure and amount of variation transmitted from generation to generation. Whether the heritable covariance structure itself remains stable or evolves rapidly is a central, yet unresolved, question in phenotypic evolution. Competing hypotheses suggest that trait covariation may be constrained by developmental and genetic architectures or, alternatively, reshaped by persistent directional selection. Here, we test whether covariance structure and evolvability are stable over macroevolutionary timescales by applying a comparative evolutionary quantitative genetics framework on primates. We quantified cranial variation using over ten thousand specimens representing 309 species and compared phenotypic covariance matrices for 57 genera within a Bayesian framework. Our results show that despite extensive morphological divergence, primates show remarkably conserved patterns of variation, modular organization, and capacity to respond to selection. Reconstruction of selection gradients across the primate radiation revealed that selection was highly structured, with preferential directions aligned with major axes of cranial variation. These results suggest that the stability of evolvability does not reflect evolutionary stasis, but rather emerges from the alignment between conserved developmental architecture and selection. Our findings demonstrate that covariance structure and the evolutionary potential it provides can persist over deep evolutionary timescales, providing a mechanistic framework for understanding how developmental systems shape the trajectories of major radiations.

evolutionary biology↗

bioRxiv2025

Invasion of new adaptive zones retains telltale signs of directional selection at macroevolutionary scales in mammals

Directional selection is often viewed as a transient force in macroevolution, with its signal eroded over time by stabilizing and fluctuating selection. Yet, transitions into new adaptive zones are predicted to impose strong and sustained selective pressures that may leave a detectable signature even across deep timescales. We test this prediction by comparing the rates of multivariate skull morphological evolution required to traverse the boundaries between adaptive zones against genetic drift expectations. Our dataset includes 11,793 specimens spanning 231 species from 12 mammalian clades, each containing unique ecological transitions into new adaptive zones. Using a quantitative genetics framework, we estimated the phenotypic distances between ancestral and derived adaptive zones and contrasted them with null expectations under genetic drift. While a few adaptive zone invasions (e.g., marsupials and rodents) are consistent with drift, most exhibit substantially elevated rates of evolution. These results suggest that directional selection has recurrently shaped mammalian cranial evolution during major ecological shifts. We propose that adaptive zone transitions represent evolutionary contexts in which adaptation leaves a persistent macroevolutionary signal, challenging the prevailing view that long-term patterns are dominated by static forces.

evolutionary biology↗

bioRxiv2023

Social network dynamics and gut microbiota composition during alpha male challenges in Colobus vellerosus

The gut microbiota of group-living animals is strongly influenced by their social interactions, but it is unclear how it responds to social instability. We investigated whether social instability associated with the immigration of new males and challenges to the alpha male position could explain differences in the gut microbiota in adult female Colobus vellerosus at Boabeng-Fiema, Ghana. During May-August 2007 and May 2008-May 2009, we collected: 1) 53 fecal samples from adult females in 8 social groups for v4 16S rRNA sequencing to determine gut microbiota composition; and 2) demographic and behavioral data ad libitum to determine male immigration, challenges to the alpha male position, and infant births and deaths. We estimated Sorensen and Bray-Curtis beta diversity indices (i.e., between-sample microbiome variation), and they were predicted by year, alpha male stability, group identity, age, and individual identity. We then created 1-m proximity networks using detailed behavioral data via focal follows of 19 adult females in 3 of these groups. Yearly 1-m proximity ties predicted adult female beta-diversity in the two socially stable groups. An alpha male takeover in the third group was associated with infant mortality and temporal variation in proximity networks. Beta-diversity among adult females was predicted by similarity in infant loss status and short-term (rather than yearly) 1-m proximity ties. Although the mechanism driving this association needs to be further investigated in future studies, our findings indicate that alpha male takeovers and social stability are associated with gut microbiota variation and highlight the importance of taking demographic and social network dynamics into account.

animal behavior and cognition↗

bioRxiv2023

Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

The high mutation rate of SARS-CoV-2 leads to emergence of several variants, some of which are resistant to vaccines and drugs targeting viral elements. Targeting host dependency factors - cell proteins required for viral replication - would help avoid resistance. However, whether different SARS-CoV-2 variants induce conserved cell responses and exploit the same core host factors is still unclear. We compared three variants of concern and observed that the host transcriptional response was conserved, differing only in kinetics and magnitude. By CRISPR screening we identified the host genes required for infection by each variant: most of the identified genes were shared by multiple variants, both in lung and colon cells. We validated our hits with small molecules and repurposed FDA-approved drugs. All drugs were highly effective against all tested variants, including delta and omicron, new variants that emerged during the study. Mechanistically, we identified ROS production as a pivotal step in early virus propagation. Antioxidant drugs, such as N-acetyl cysteine (NAC), were effective against all variants both in human lung cells, and in a humanised mouse model. Our study supports the use of available antioxidant drugs, such as NAC, as a general and effective anti-COVID-19 approach.

microbiology↗

bioRxiv2022

Developmental rules of primate dental evolution align microevolution with macroevolution

Macroevolutionary biologists have classically rejected the notion that higher level patterns of divergence arise through microevolutionary processes acting within populations. For morphology, this consensus partly derives from the inability of quantitative genetics models to correctly predict the behavior of evolutionary processes at the scale of millions of years. Developmental studies (evo-devo) have been proposed to reconcile micro and macroevolution. However, there has been little progress in establishing a formal framework to apply evo-devo models of phenotypic diversification. Here, we reframe this issue by asking if using evo-devo models to quantify biological variation can improve the explanatory power of comparative models, thus helping us bridge the gap between micro- and macroevolution. We test this prediction by evaluating the evolution of primate lower molars in a comprehensive dataset densely sampled across living and extinct taxa. Our results suggest that biologically-informed morphospaces alongside quantitative genetics models allow a seamless transition between the micro and macro scales, while biologically uninformed spaces do not. We show that the adaptive landscape for primate teeth is corridor-like, with changes in morphology within the corridor being nearly neutral. Overall, our framework provides a basis for integrating evo-devo into the modern synthesis, allowing an operational way to evaluate the ultimate causes of macroevolution.

evolutionary biology↗

bioRxiv2021

The mechanosensitive TRPV2 calcium channel controls melanoma invasiveness and metastatic potential.

Discovery of therapeutic targets against metastasis is of primary importance since being the main cause of cancer-related death. Melanoma is a highly aggressive cancer endowed with a unique capacity of rapidly metastasizing. Deregulation of calcium homeostasis has been involved in numerous cellular metastatic behaviors, although the molecular determinants supporting these processes often remain unclear. Here, we evidenced a prominent expression of the plasma membrane TRPV2 calcium channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic progression and dissemination. In vitro as well as in vivo, TRPV2 activity was sufficient to confer both migratory and invasive phenotypes to non-invasive melanoma cells, while conversely upon TRPV2 silencing, highly metastatic melanoma cells failed to retain their malignant behaviors. We established a model whereupon activation of the mechanosensitive TRPV2 channel, localized in highly dynamic nascent adhesion clusters, directly regulates calpain-dependent cleavage of the adhesive protein talin together with F-actin network. By operating at the crossroad of the tumor microenvironment and the intracellular machinery, mechanosensitive TRPV2 channel controls melanoma cells aggressiveness. Finally in human melanoma tumor samples, TRPV2 overexpression represents a molecular marker of advanced malignancy and bad prognosis, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma. SignificanceOne essential feature of metastatic cells is enhanced motility and invasiveness. This study evidences TRPV2 channel control over metastatic melanoma invasiveness, highlights new migration regulatory mechanisms, and reveals this channel as a biomarker and migrastatic target for the treatment of advanced melanoma.

cancer biology↗

bioRxiv2020

Fine tuning of calcium constitutive entry by optogenetically-controlled membrane polarization: impact on cell migration.

Anomalies in constitutive calcium entry (CCE) have been commonly attributed to cell dysfunction in pathological conditions such as cancer. Calcium influxes of this type rely on channels, such as TRP, to be constitutively opened and strongly depend on membrane potential and calcium driving force. We developed an optogenetic approach based on expression of the halorhodopsin chloride pump to study CCE in non-excitable cells. Using C2C12 cells, we found that halorhodopsin can be used to achieve a finely-tuned control of membrane polarization. Escalating the membrane polarization by incremental changes in light led to a concomitant increase in CCE through TRPV2 channels. Moreover, light-induced calcium entry through TRPV2 channels promoted cell migration. Our study shows for the first time that by modulating CCE and related physiological responses such as cell motility, halorhodopsin serves as a potentially powerful tool that could open new avenues for the study of CCE and associated cellular behaviors.

cell biology↗