Abstract Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of phenotypic heterogeneity. Although the predominant focus of scRNA-seq analyses has been assessing gene expression changes, several approaches have been proposed in recent years to identify changes at the DNA level from scRNA-seq data. In this study, we evaluated the relative performance of six strategies for calling single-nucleotide variants from scRNA-seq data using 381 single-cell transcriptomes from five cancer patients. Specifically, we focused on the quality of the inferred genotypes and the resulting single-cell phylogenies. We found that scAllele, Monopogen, and Monovar consistently returned phylogenetically informative genotype calls, providing more precise signals of discrimination between tumor and normal cells within heterogeneous samples and among distinct subclonal lineages in longitudinal samples. In addition, we evaluated the evolution of gene expression along the cell phylogenies. While most transcriptomic variation was very plastic and did not correlate with the cell phylogeny, a group of genes associated with cell cycle processes showed a strong phylogenetic signal in one of the patients, underscoring a potential link between gene expression patterns and lineage-specific traits in the context of cancer progression. In summary, our study highlights the potential of scRNA-seq data for inferring cell phylogenies to decipher the evolutionary dynamics of cell populations.
We studied sequence variation in 16S rDNA in 204 individuals from 37 populations of the land snail Candidula unifasciata (Poiret 1801) across the core species range in France, Switzerland, and Germany. Phylogeographic, nested clade, and coalescence analyses were used to elucidate the species evolutionary history. The study revealed the presence of two major evolutionary lineages that evolved in separate refuges in southeast France as result of previous fragmentation during the Pleistocene. Applying a recent extension of the nested clade analysis (Templeton 2001), we inferred that range expansions along river valleys in independent corridors to the north led eventually to a secondary contact zone of the major clades around the Geneva Basin. There is evidence supporting the idea that the formation of the secondary contact zone and the colonization of Germany might be postglacial events. The phylogeographic history inferred for C. unifasciata differs from general biogeographic patterns of postglacial colonization previously identified for other taxa, and it might represent a common model for species with restricted dispersal.
Ayala, D. E.1; Hermida, R. C.1; Mojon, A.1; Fernandez, J. R.1; Alonso, I.1; Aguilar, M. F.2; Codesido, J.2; Iglesias, M.2 Author Information