We present a stochastic model for tandem duplications and point mutations that can be used to estimate relative mutation rates and the total number of mutations from a single sequence. Important parameters of the model include the probability of a point mutation and the probability of a tandem duplication of a given length. Our model indicates that if the probability of point mutations is insig...

In recent theoretical and experimental work on schemata in genetic programming we have proposed a new simpler form of crossover in which the same crossover point is selected in both parent programs. We call this operator one-point crossover because of its similarity with the corresponding operator in genetic algorithms. One point crossover presents very interesting properties from the theory po...

Negative cofactor 2 (NC2) is a dimeric histone-fold complex that represses RNA polymerase II transcription through binding to TATA-box-binding protein (TBP) and inhibition of the general transcription factors TFIIA and TFIIB. Here we study molecular mechanisms of repression by human NC2 in vivo in yeast. Yeast NC2 genes are essential and can be exchanged with human NC2. The physiologically rele...

Yeast phosphofructokinase is an oligomeric enzyme whose detectable activity in vitro depends on its hetero-octameric structure. Here we provide data demonstrating that an alanine residue at positions 874 (for the PFK1-encoded alpha-subunit) or 868 (for the PFK2-encoded beta-subunit) is crucial to achieve this structure. Thus subunits carrying substitutions by either aspartate or lysine of this ...

Membrane fusion and budding are key steps in the life cycle of all enveloped viruses. Semliki Forest virus (SFV) is an enveloped alphavirus that requires cellular membrane cholesterol for both membrane fusion and efficient exit of progeny virus from infected cells. We selected an SFV mutant, srf-3, that was strikingly independent of cholesterol for growth. This phenotype was conferred by a sing...

The P23T mutant of human D-crystallin (HGD) is associated with cataract. We have previously investigated the solution properties of this mutant, as well as those of the closely related P23V and P23S mutants, and shown that although mutations at site 23 of HGD do not produce a significant structural change in the protein, they nevertheless profoundly alter the solubility of the protein. Remarkab...

23 Human coronaviruses (HCoV) are recognized respiratory pathogens and some 24 strains, including HCOV-OC43, can infect human neuronal and glial cells of the central 25 nervous system (CNS), and activate neuroinflammatory mechanisms. Moreover, 26 HCoV-OC43 is neuroinvasive, neurotropic and neurovirulent in susceptible mice, where it 27 induces a chronic encephalitis. Herein, we show that a sing...

Precise genome editing in livestock is of great value for the fundamental investigation of disease modeling. However, genetically modified pigs carrying subtle point mutations were still seldom reported despite the rapid development of programmable endonucleases. Here, we attempt to investigate single-stranded oligonucleotides (ssODN) mediated knockin by introducing two orthologous pathogenic m...