Norell, M. A. | Search bioRxiv

bioRxiv2020

Selection for Decreased BRCA2 Functional Activity in Homo sapiens After Divergence from the Chimpanzee-Human Last Common Ancestor

Humans have an increased incidence of epithelial neoplasia compared to non-human primates. We performed a comparative analysis of 21 non-human primate genomes and 54 ancient human genomes to identify variations in known cancer genes that may explain this difference. We identified 299 human-specific fixed non-silent single nucleotide polymorphisms. Bioinformatics analyses for functional consequences identified a number of variants predicted to have altered protein function, one of which was located at the most evolutionarily conserved domain of human BRCA2. This variant, in which a polar threonine residue replaces a hydrophobic methionine residue to codon 2662 within the DSS1 binding domain, decreases the interactions of BRCA2 with other proteins, specifically the binding of BRCA2 and RAD51, as well as the repairing ability of cells for DNA double-strand breaks. We conclude that a 20% reduction in BRCA2 DNA repair ability was positively selected for in the course of human evolution. One Sentence SummaryReduction of BRCA2 functional activity has been selected for during human evolution since the chimpanzee-human last common ancestor.

evolutionary biology↗

bioRxiv2020

Powered flight potential approached by wide range of close avian relatives but achieved selectively

Evolution of birds from non-flying theropod dinosaurs is a classic evolutionary transition, but a deeper understanding of early flight has been frustrated by disagreement on the relationships between birds (Avialae) and their closest theropod relatives. We address this through a larger, more resolved evolutionary hypothesis produced by a novel automated analysis pipeline tailored for large morphological datasets. We corroborate the grouping of dromaeosaurids + troodontids (Deinonychosauria) as the sister taxon to birds (Paraves), as well as the recovery of Anchiornithidae as basalmost avialans. Using these phylogenetic results and available data for vaned feathered paravians, maximum and minimum estimates of wing loading and specific lift calculated using ancestral state reconstruction analysis are used as proxies for the potential for powered flight through this transition. We found a broad range of paravian ancestors with estimates approaching values that are indicative of powered flight potential. This suggests that prior to the evolution of flight there was a wider extent of experimentation with wing-assisted locomotion among paravians than previously appreciated. We recovered wing loading and specific lift estimates indicating the potential for powered flight among fossil birds as well as unenlagiine and microraptorine dromaeosaurids. In the context of our phylogeny and of Mesozoic palaeogeography, our results suggest that the potential for powered flight originated three or more times from a broad range of ancestors already nearing this potential, providing a well-supported scenario for the origin of theropod flight to further explore.

paleontology↗