Haploinsufficiency, wherein a single functional copy of a gene is insufficient to maintain normal function, is a major cause of dominant disease. Human disease studies have identified several hundred haploinsufficient (HI) ...

Deleterious mutations are considered a major impediment to adaptation, and there are straightforward expectations for the rate at which they accumulate as a function of population size and mutation rate. In a simulation ...

The molecular nature of biological variation is not well understood. Indeed, many questions persist regarding the types of molecular changes and the classes of genes that underlie morphological variation within and among ...

In eukaryotes, gene expression is a complex, multi-step process involving transcription, splicing, translation, and post-translational modifications. At each individual step, errors can occur that lead to nonfunctional and ...

Lethal mutagenesis is a promising new antiviral therapy that kills a virus by raising its mutation rate. One potential shortcoming of lethal mutagenesis is that viruses may resist the treatment by evolving genomes with ...

During the course of evolution, new proteins are produced very largely as the result of gene duplication, divergence and, in many cases, combination. This means that proteins or protein domains belong to families or, in ...

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as ...

Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelments hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most ...

In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little ...