Miller, S. E. | Search bioRxiv

bioRxiv2018

Evolutionary dynamics of recent selection for enhanced social cognition

Cognitive abilities can vary dramatically among species though little is known about the dynamics of cognitive evolution. Here we demonstrate that recent evolution of visual individual recognition in the paper wasp Polistes fuscatus is the target of arguably the strongest positive selective pressure in the species recent history. The most extreme selective sweeps in P. fuscatus are associated with genes known to be involved in long-term memory formation, mushroom body development and visual processing - all traits that have recently evolved in association with individual recognition. Cognitive evolution appears to have been driven initially by selection on standing variation in perceptual traits followed by both hard and soft sweeps on learning and memory. Evolutionary modeling reveals that intense selection as observed in P. fuscatus is likely the norm during the early stages of cognitive evolution. These data provide insight into the dynamics of cognition evolution demonstrating that social selection for increased intelligence can lead to rapid multi-genic adaptation of enhanced recognition abilities.

animal behavior and cognition↗

bioRxiv2017

Germline loss of MBD4 predisposes to leukaemia due to a mutagenic cascade driven by 5mC

Cytosine methylation is essential for normal mammalian development, yet also provides a major mutagenic stimulus. Methylcytosine (5mC) is prone to spontaneous deamination, which introduces cytosine to thymine transition mutations (C>T) upon replication1. Cells endure hundreds of 5mC deamination events each day and an intricate repair network is engaged to restrict this damage. Central to this network are the DNA glycosylases MBD42 and TDG3,4, which recognise T:G mispairing and initiate base excision repair (BER). Here we describe a novel cancer predisposition syndrome resulting from germline biallelic inactivation of MBD4 that leads to the development of acute myeloid leukaemia (AML). These leukaemias have an extremely high burden of C>T mutations, specifically in the context of methylated CG dinucleotides (CG>TG). This dependence on 5mC as a source of mutations may explain the remarkable observation that MBD4-deficient AMLs share a common set of driver mutations, including biallelic mutations in DNMT3A and hotspot mutations in IDH1/IDH2. By assessing serial samples taken over the course of treatment, we highlight a critical interaction with somatic mutations in DNMT3A that accelerates leukaemogenesis and accounts for the conserved path to AML. MBD4-deficiency was also detected, rarely, in sporadic cancers, which display the same mutational signature. Collectively these cancers provide a model of 5mC-dependent hypermutation and reveal factors that shape its mutagenic influence.

cancer biology↗