PLOS Biology: New Articles

1. High-resolution paleobiome reconstructions highlight ecological and historical dynamics underpinning global terrestrial vertebrate diversity

   by Alexander Skeels, Julian Rogger, Marcel Cardillo, Alexander Farnsworth, Daniel J. Lunt, Dirk Nikolaus Karger

   Past climate change has repeatedly reshaped Earth’s biomes, yet how their expansion and contraction influence biodiversity patterns through time remains unclear. Competing hypotheses propose that either historical biome area has a strong influence on diversity, or that biodiversity responds rapidly to environmental change, such that present-day biome area and energy are sufficient to explain diversity patterns. Progress in testing these ideas has been limited by sparse and inconsistent proxy data and the coarse resolution of existing paleoclimate models. Here, we reconstructed global biome histories for the Cenozoic (66–0 Ma) by downscaling five different paleoclimate simulations. Estimates of change in biome area through time were generally consistent among alternative climate models and with the empirical proxy record. Accounting for variation among models, we found that present-day area and energy were consistently better predictors of vertebrate diversity than historical measures. These findings suggest biodiversity tracks the ecological limits set by shifting biomes, leaving sparse legacy of past dynamics. Our results highlight the importance of integrating multiple paleoclimate reconstructions when assessing the historical drivers of biodiversity.
2. Dynamism under the hood: Coevolutionary maintenance of variation in hosts and parasites

   by Andrea L. Graham, David A. Chang van Oordt

   Why do hosts and parasites vary so much? A new study in PLOS Biology reveals that infection outcomes strongly depend upon interacting effects of host and parasite genotypes, offering an evolutionary explanation for profound and persistent variability. Why do hosts and parasites vary so much? This Primer explores a new study in PLOS Biology revealing that infection outcomes strongly depend upon interacting effects of host and parasite genotypes, offering an evolutionary explanation for profound and persistent variability.
3. Host–virus interactions dominate fitness and conceal additive genetic variation

   by Aleksei Belyi, Yiyang Du, Alastair J. Wilson, Ben Longdon, Francis M. Jiggins

   Host–parasite coevolution is expected to generate strong selection for resistance and infectivity that has the potential to erode genetic variation. Despite this, natural populations often retain extensive genetic variation in these traits. Genotype-by-genotype interactions on fitness can generate negative frequency-dependent selection, which helps maintain this variation by preventing any host or pathogen genotype from retaining a permanent advantage. Because these interactions place genetic variance in the interaction term rather than in additive differences among hosts or pathogens, that variance is masked from directional selection and can remain ‘cryptic’. Here we combine coevolutionary modelling with large‑scale experimental infection assays to quantify how host-pathogen interactions structure fitness variance in a vertically transmitted virus system, Drosophila melanogaster and sigma virus. Simulations show that coevolution typically erodes additive genetic variance in host and pathogen fitness, concentrating variance in host-virus interaction terms. Consistent with these predictions, experiments spanning 90 host-virus genotype combinations reveal that transmission, viral load, and virulence are overwhelmingly governed by host-virus genetic interactions rather than host or virus main effects. As a result, neither host resistance alleles nor viral genotypes confer consistently higher fitness across genetic backgrounds. Interactions tend to be sex‑specific, further limiting heritable fitness variation. Our results demonstrate that coevolution can substantially mask heritable genetic variation from directional selection by rendering fitness context-dependent. This extensive cryptic genetic variation may be revealed either when ecological or evolutionary conditions shift, or when the process of coevolution itself alters the direction of selection. This demonstrates the need to account for genotype-specific interactions when forecasting evolutionary responses.
4. A cortical semantic map integrates fractions and integers in the human brain

   by Daniela Valério, Samuel Debray, Alireza Karami, Maxime Cauté, Nicolás Gravel, Stanislas Dehaene

   How does the human brain represent the meaning of abstract symbols? Some theories postulate the existence of semantic spaces where concepts occupy positions that reflect their conceptual relationships. In the number domain, psychological evidence suggests that integers are represented along a mental number line which, with education, integrates higher-level number concepts such as fractions. To test this hypothesis, we recorded whole-brain 7T fMRI responses to integer and fraction symbols during an active magnitude comparison task designed to engage magnitude processing. Consistent with predictions, we found both behavioral and neural numerical distance effects. Activation vectors in intraparietal, inferior temporal, prefrontal, hippocampal, and parahippocampal cortices formed a two-dimensional semantic space organized by numerical magnitude and domain (fractions versus integers). Gaussian fits revealed a topographic map of numerical preferences in the anterior inferior parietal cortex, common to both domains. Our results suggest that, when educated adults engage in an explicit magnitude comparison task, their brain can construct an ordered representation that integrates fractions and integers, with a topographic organization in the anterior IPS/IPL.
5. A macrophage-targeted TIMD4 Peptide-Nanoparticle attenuates colitis symptoms and monocyte recruitment in a mouse model

   by Huimin Liu, Yuzhen Wang, Ruiqing Yu, Kexin Liu, Dezhi Zheng, Bo Wang, Yuan Chang, Bing Liu, Xuetian Yue, Zhuanchang Wu, Chunyang Li, Xiaohong Liang, Chunhong Ma, Guohua Liu, Jianhua Li, Leiqi Xu, Lifen Gao

   Macrophages play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). T-cell immunoglobulin and mucin domain-containing molecule 4 (TIMD4) is involved in the regulation of tissue-resident macrophages. TIMD4 expression is elevated in colonic tissues from patients with ulcerative colitis (UC) and mice with dextran sulfate sodium (DSS)-induced colitis, but its role in IBD pathogenesis remains unclear. In this study, we found that Timd4 deficiency aggravated DSS-induced colitis, accompanied by increased infiltration of monocytes into the colonic tissues. Treatment with a CCR2 antagonist attenuated colonic inflammation and reduced monocyte infiltration into colonic tissues in Timd4 KO mice. Mechanistically, in vitro studies revealed that TIMD4 stabilized the LKB1-STRAD-MO25 complex via its intracellular domain, thereby activating the AMPK pathway and suppressing NF-κB-dependent chemokine production in macrophages. Based on these findings, we designed a TIMD4-derived peptide and developed a macrophage-targeted nanoparticle system (T4_(365–378)‑NPs). Treatment with T4_(365–378)-NPs reduced P65 phosphorylation and attenuated DSS-induced colitis in mice. Treatment with either T4_(365–378)-NPs or the CCR2 antagonist attenuated DSS-induced colitis, and no statistically significant differences in the assessed outcomes were detected between the two groups. Administration of T4_(365–378)-NPs before DSS exposure also attenuated subsequent colitis. Furthermore, combining the T4_(365–378)‑NPs with anti-α4β7 or anti-TNF-α antibodies produced greater improvements than either monotherapy in the DSS-induced colitis model. These findings support further preclinical evaluation of TIMD4-derived peptide delivery as a potential therapeutic approach for intestinal inflammation.