bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.12.28.522128

Defining ancestry, heritability and plasticity of cellular phenotypes in somatic evolution

Schiffman, J. S.·D'Avino, A. R.·Prieto, T.·Potenski, C.·Fan, Y.·Hara, T.·Suva, M. L.·Landau, D. A.
View original source ↗Export metadata ↓

Abstract

The broad application of single-cell RNA sequencing has revealed transcriptional cell state heterogeneity across diverse healthy and malignant somatic tissues. Recent advances in lineage tracing technologies have further enabled the simultaneous capture of cell transcriptional state along with cellular ancestry thus enabling the study of somatic evolution at an unprecedented resolution; however, new analytical approaches are needed to fully harness these data. Here we introduce PATH (Phylogenetic Analysis of Transcriptional Heritability), an analytical framework, which draws upon classic approaches in species evolution, to quantify heritability and plasticity of somatic phenotypes, including transcriptional states. The PATH framework further allows for the inference of cell state transition dynamics by linking a model of cellular evolutionary dynamics with our measure of heritability versus plasticity. We evaluate the robustness of this approach by testing a range of biological and technical features in simulations of somatic evolution. We then apply PATH to characterize previously published and newly generated single-cell phylogenies, reconstructed from either native or artificial lineage markers, with matching cellular state profiling. PATH recovered developmental relationships in mouse embryogenesis, and revealed how anatomic proximity influences neural relatedness in the developing zebrafish brain. In cancer, PATH dissected the heritability of the epithelial-to-mesenchymal transition in a mouse model of pancreatic cancer, and the heritability versus plasticity of transcriptionally-defined cell states in human glioblastoma. Finally, PATH revealed phenotypic heritability patterns in a phylogeny reconstructed from single-cell whole genome sequencing of a B-cell acute lymphoblastic leukemia patient sample. Altogether, by bringing together perspectives from evolutionary biology and emerging single-cell technologies, PATH formally connects the analysis of cell state diversity and somatic evolution, providing quantification of critical aspects of these processes and replacing qualitative conceptions of "plasticity" with quantitative measures of cell state transitions and heritability.

Source connections

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Schiffman, J. S., D'Avino, A. R., Prieto, T., Potenski, C., Fan, Y., Hara, T., Suva, M. L., Landau, D. A.. 2022-12-30. Defining ancestry, heritability and plasticity of cellular phenotypes in somatic evolution. https://doi.org/10.1101/2022.12.28.522128

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Measuring the strength of selection and pollen limitation on flower colour along an urban rural cline in Hesperis matronalis

Closely located urban and rural environments can differ in temperature, water availability, species diversity, and more. As a result, organisms in urban environments may experience different selection than those in rural environments. We investigated whether differences in selection might explain a previously identified urban-rural cline in the flower colour of Hesperis matronalis (dame's rocket). To explore whether plants in urban and rural environments are impacted by possible differences in pollinator availability or behavior, we performed a pollen supplementation experiment. We did not detect an effect of pollen supplementation on seed production in either setting (urban or rural), indicating that there is limited opportunity for any differences in pollinator availability or visitation to explain the cline in flower colour. We also measured the strength of selection acting on flower colour to investigate if it differed between urban and rural populations. In all but one population, we failed to detect significant linear or non-linear selection on flower colour, suggesting that selection on flower colour does not differ between urban and rural populations. Our results suggest that the urban-rural flower colour cline is likely not caused by differences in selection or pollen-limitation and may be due to stochastic forces.

evolutionary biology↗
bioRxiv2026

An elongated lifespan is associated with higher oxidative protection of flight tissue in Heliconiini butterflies

Evolutionary theories of ageing often invoke trade-offs in resource allocation between somatic maintenance and other important physiological functions. One proposed mechanistic mediator of these trade-offs is oxidative stress, which arises from an imbalance between an organism's production of reactive oxygen species and its ability to detoxify them. Accordingly, many long-lived species across the animal kingdom show evidence for resistance to oxidative stress. However, it can be difficult to associate lifespan differences with oxidative phenotypes when comparing species across wide taxonomic distances, which may also show large differences in physiology. Butterflies in the long-lived Heliconius genus show a 3-fold lifespan extension and slowed ageing in comparison with their close relatives in the Heliconiini tribe, to whom they are phylogenetically, ecologically, and physiologically similar. However, proximate explanations for this extended longevity are currently lacking. Here, we leverage the neat comparative framework between Heliconius hecale and Dryas iulia, a shorter-lived Heliconiini outgroup, to test whether the observed lifespan differences between the two species are associated with differences in oxidative physiology. Our findings suggest superior oxidative protection of thoracic tissue in the longer-lived H. hecale compared to D. iulia, as evidenced by increased superoxide dismutase activity, increased total antioxidant capacity, and a corresponding reduction in lipid peroxidation in this tissue. Considering the metabolic demands of insect flight, we suggest that this oxidative phenotype may contribute to the extended longevity of Heliconius by enhancing protection of thoracic tissues against oxidative damage, representing a plausible proximate pro-longevity mechanism in this genus.

evolutionary biology↗
bioRxiv2026

Both genetic and social inheritance influence female aggressive and submissive behavior in a wild primate

Agonistic interactions are important determinants of resource access in wild animals, but their genetic basis remains poorly understood. Here we use a quantitative genetics approach to estimate the heritability of aggressive and submissive behavior of wild female baboons, considering relative rates of both individual and dyadic aggression and submission. To control for the social inheritance that creates kin-based dominance hierarchies, we implemented a multi-matrix model that included a social status similarity matrix alongside the additive genetic matrix. Despite a substantial contribution of social inheritance, especially for submissive behavior, we found heritable components for both aggressive and submissive behavior (h2=0.21 and h2=0.09-0.11, respectively). In dyadic models, aggressive behavior was primarily influenced by the aggressor's genotype (a direct genetic effect), while submissive behavior was primarily affected by the social partner's genotype (an indirect genetic effect). Finally, we found evidence for a negative genetic (but not phenotypic) correlation between aggressive and submissive behavior within dyads, and a negative genetic correlation between submissive behavior and eliciting submissive behavior. Together, our results highlight how direct genetic, indirect genetic, and social inheritance effects combine to influence primate social behavior.

evolutionary biology↗