Dube, A. | Search bioRxiv

bioRxiv2025

Novel integrated risk index reveals uneven impact of climate change on fascioliasis risk across Africa and Europe

Fascioliasis, a zoonotic parasitic disease caused by the liver flukes Fasciola hepatica and Fasciola gigantica, poses a significant threat to livestock and human health globally. Climate change is altering the transmission dynamics of this disease; however, the direction and magnitude of this change remain uncertain due to a lack of mechanistically grounded predictions at continental scale. In this study, we developed a novel risk index to assess how climate change may affect the potential for fascioliasis transmission across Africa and Europe. The index integrates the following three components that together capture the environmental requirements for Fasciola transmission: the temperature dependence of the parasite transmission; climatic suitability for the snail intermediate host; and availability of freshwater habitats. To estimate these components, we used data from published experimental studies, thousands of snail occurrence records, and both mechanistic and correlative modelling approaches. We predict that climate change will generally reduce fascioliasis risk across most of the ranges of the two investigated liver fluke species, albeit with marked geographical differences. The transmission risk of F. gigantica is predicted to decrease in the Sahel and West Africa, due to above-optimal temperatures for parasite transmission and climatic suitability for the intermediate hosts. However, risk for F. hepatica transmission is projected to increase in parts of Northern Europe, Scandinavia, and Iceland, where livestock densities are high. We also find that the potential for hybridization between F. hepatica and F. gigantica may decline due to reduced geographic overlap in areas that are highly suitable for transmission. By providing a scalable, ecologically informed framework for predicting fascioliasis risk under climate change, this study lays the groundwork for improved local risk assessment. Our results provide a more nuanced perspective on the potential impact of climate change on fascioliasis transmission, showing that this will be highly uneven across Africa and Europe. Author summaryFascioliasis is a snail-borne, zoonotic disease that affects both humans and livestock, causing major health burden and economic losses worldwide. The liver flukes that cause the disease use freshwater snails as their intermediate hosts. They therefore require aquatic habitats and suitable temperatures to complete their life cycle. Climate change altering these conditions; however, it is unclear how this will affect transmission of liver flukes in the future. Here we develop a new risk index that combines three key environmental factors of importance for liver fluke transmission: how suitable temperatures are for parasite transmission, the climatic suitability for snail hosts, and the availability of water. We mapped current and projected future transmission risk for two main species, Fasciola hepatica and Fasciola gigantica, across Africa and Europe. Different from what has been predicted by earlier studies, our results suggest that transmission risk will decline in across most of the range of both species. This will have particularly big impacts in areas where livestock densities are high, including the Sahel region. In northern Europe, transmission risk increases slightly. This study also provides a modelling framework and novel ecological knowledge that can be used to assess risk of transmission at local and continental scale.

ecology↗

bioRxiv2025

Paralog interference preserves genetic redundancy

Models of gene duplication often assume that loss-of-function mutations neutrally promote the return to the ancestral singleton state. They thus ignore the potential functional interference between duplicated proteins stemming from their physical interactions. Here, we show that for heteromerizing paralogs, such interference potentiates negative selection on loss-of-function mutations. This effect maintains genetic redundancy over longer timescales depending on the rate and severity of loss-of-function mutations. We experimentally estimate that around 6% of deleterious amino acid substitutions for a representative tetrameric protein interfere with a second copy. Interfering substitutions typically disrupt either catalysis or the final step of protein complex assembly, with varying degrees of severity. Our work shows that paralog interference renders the negative effects of loss-of-function mutations visible to purifying selection, contributing to the preservation of genetic redundancy.

evolutionary biology↗

bioRxiv2019

The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs

Many paralogs derive from the duplication of genes encoding homomeric proteins. Such duplication events lead to the formation of homomers and heteromers, thus creating new structures from a single event. We exhaustively characterize this phenomenon using the budding yeast protein-protein interaction network. We observe that paralogs that heteromerize are very frequent and less functionally diverged than those that lost this property, raising the possibility that heteromerization prevents functional divergence. Using in silico evolution, we show that for homomers and heteromers that share binding interfaces, mutations on one complex have pleiotropic effects on the other complex, resulting in highly correlated responses to selection. As a result, heteromerization could be preserved indirectly due to selection for the maintenance of homomers. By integrating data on gene expression and protein localization, we find that regulatory evolution could play a role in overcoming these structural pleiotropic effects and in allowing paralog functional divergence.

evolutionary biology↗