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Lecture

Evolutionary walks on fitness landscapes: insights on adaptation and resistance

Description

This lecture by Eugene Shakhnovich explores the concept of fitness landscapes in evolutionary biology, focusing on the biophysical fitness landscape of E. coli DHFR. The lecture covers topics such as the relationship between molecular properties and fitness, the impact of mutations on stability and activity, and the prediction of antibiotic resistance based on molecular properties. Shakhnovich discusses the evolutionary dynamics of resistance, the role of protein quality control in resistance, and the pleiotropic effects of mutations in DHFR. The lecture concludes with a discussion on the implications of mutations in DHFR at molecular, systems, and macroscopic levels.

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Related concepts (32)

Fitness landscape

In evolutionary biology, fitness landscapes or adaptive landscapes (types of evolutionary landscapes) are used to visualize the relationship between genotypes and reproductive success. It is assumed that every genotype has a well-defined replication rate (often referred to as fitness). This fitness is the "height" of the landscape. Genotypes which are similar are said to be "close" to each other, while those that are very different are "far" from each other.

Antimicrobial resistance

Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials (drugs used to treat infections). All classes of microbes can evolve resistance where the drugs are no longer effective. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. Protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance.

Antibiotic

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics.

Mutation

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication (translesion synthesis).

Evolutionary biology

Evolutionary biology is the subfield of biology that studies the evolutionary processes (natural selection, common descent, speciation) that produced the diversity of life on Earth. It is also defined as the study of the history of life forms on Earth. Evolution holds that all species are related and gradually change over generations. In a population, the genetic variations affect the phenotypes (physical characteristics) of an organism. These changes in the phenotypes will be an advantage to some organisms, which will then be passed onto their offspring.

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