Evolutionary_Genetics

Evolution: The process of organismal change and diversification through generational time from shared common ancestry. Darwin: ‘Descent with modification’.

• Evolution is not the only process generating seemingly complex forms (e.g. snowflakes)

• Originally evolution was observed at the level of the phenotype. It is important to recognize that the phenotype is determined by the genotype encoded in the DNA polymer (central dogma) interacting with the cell and the environment. Ultimately genetic variation is the raw material for evolution.

• Evolution is most readily visible in higher order taxa; yet, it unfolds through inheritance with modification of individuals at the population level.

• Evolution does not progress towards a goal, nor is it just random fluctuation.

• Evolution ≠ natural selection ≠ adaptation.

• Evolution did not just happen in the past. It is ongoing here and now

• Hierarchical organization of life. Assuming a historical process of branching and diverging best reflects biological reality of species and higher-order groups with ever decreasing similarity. It is superior to any other organizing system proposed so far.

• Homology. Similarity of structure despite differences in function is best explained by shared ancestry, not by best design.

• Embryological similarities. Homologous characters not needed at later life stages appear transitorily during embryological development. This can only be understood by shared ancestry.

• Vestigial characters. There are numerous examples of ancestral features that are degenerated and of no use to the remnant organism. Cave dwelling fish e.g. display eyes in every stage of degeneration.

• Convergence. Functionally similar features often evolved independently and differ profoundly in structure. This provides evidence for adaptation by natural selection and cannot be understood by the hypotheses of optimal design.

• Suboptimal design. Indeed, many structures show suboptimal design (e.g. blind spot in human eye) and can only be understood by historical constraint. Evolution simply has to work with the variation present at the time.

• Geographic distributions. The distributions of many taxa align well with what we know from the movement of plate tectonics and don’t make sense without assuming contiguous change from a common ancestor.

• Intermediate forms. The hypothesis of evolution proceeding by gradual small change is well supported by intermediate forms, both in living organisms (some snakes still have vestigial legs) and fossils (e.g. Archaeopterix).

• Fossils. Though incomplete, the fossil record in conjunction with radioactive dating clearly demonstrates that evolution is a long, historical process of change. Dinosaurs are simply not found in the same strata as humans.

• Molecular evidence. Common ancestry is seen in a large variety of molecular properties (codon usage, basic molecular machinery, organelles, etc.) and homologies displaying similar functionality across millions of years (if you insert a mouse ‘eye’ gene into drosophila it will start making an eye providing evidence for a shared bilaterian ancestor).

- heritable trait variation

- overproduction (but fixed resources leading to selection)

- variation in lifetime reproductive success linked to variation in the trait

1953

Motoo Kimura 1968

This theory states that “the great majority of evolutionary changes at the molecular level (...) are caused not by Darwinian selection, but by random drift of selectively neutral or nearly neutral variants”

Tomoko Ohta refined the Neutral Theory (Nearly Neutral Theory) allowing for mutations with continuous fitness effects (not only with dichotomous effects neutral or so strong negative that purged immediately); slightly deleterious (advantageous) mutations also possible. This addition has the important consequence that the efficacy of selection depends on population size.

Co-inherited allelic combinations of more than one locus are called haplotypes. A specific set of haplotype combinations in a diploid are called diplotypes.

Eine somatische Zelle ist eine Körperzelle, aus der im Unterschied zu den Zellen der Keimbahn keine Geschlechtszellen (Gameten) hervorgehen können.

Mutation thus introduces genetic polymorphism (occurrence of several allelic states) into the population that segregates until the novel allele is lost or has reached fixation

Because of these relaxed conditions, the 3rd base pair is usually a synonymous site, whereas the 1st and the 2nd sites are non-synonymous.

However, there are two codons which have no tolerance for nucleotide substitutions: UGG coding for tryptophan and AUG coding for methionine exclusively exhibit non-synonymous sites

Silent mutations do not affect the amino acid sequence of a protein (e.g. TCT (Ser) > TCC (Ser)). They may occur in non-coding parts or at synonymous sites. Mutations that change a single amino acid are called missense mutations (e.g. TCT (Ser) > GCT (Ala)), mutations resulting in a premature stop codon nonsense mutations (e.g . UGC > UGA).

reversal of DNA order. Inversions spanning the centromere are called pericentric, inversions restricted to one chromosomal arm are called paracentric. Both types often produce errors during meiosis.

(1) there are an infinite number of sites where mutations can occur

(2) every new mutation occurs at a novel site

Under natural conditions and depending on the organism the mutation rate is generally low enough that a locus / site is only affected once by a mutation until it has reached fixation. On a per nucleotide basis they range from 10-4 per generation in RNA viruses that lack proof reading mechanisms to 10-10 in bacteria and nematodes, with a current estimate in humans of about 0.3-1 10-9 mutations site-1 year -1 – 0.7-2 10-8 mutations site-1 generation -1 or assuming a generation time of 20 years.

a) Pedigree-based approaches constitute the shortest timescale at which mutations can be measured. By scoring the alleles of the parents and the offspring, novel mutations that have arisen in the parents’ germ line can be directly scored.

b) Mutation accumulation lines assess mutations over somewhat larger timescales. New mutations are scored after several generations (generally of bacteria or other microorganisms) have been proliferated in the lab. There is a risk of underestimating mutations that are deleterious to their carrier. Experiments have to be designed to minimize the effect of selection.

c) Comparative genetic approaches are an indirect way of measuring mutation rates averaged over many generations by simply counting the number of (base pair) differences between homologous genes relative to the number of generations that have elapsed. This method depends on the Neutral Theory of Evolution specifying the per generation mutation rate equals the proportion of base pairs that differ between two species, divided by twice the number of generations since their common ancestor. This assumption only holds for selectively neutral sites, and often it is difficult to estimate the time to the most recent common ancestor (TMRCA) as well as the generation time.

non-degenerate -> different

2-fold egenerate -> bit different

4-fold degenerate -> 4 codons for same aa

Allele pairs separate (segregate) during game formation, then randomly unite at fertilization

Alleles at two (or more) different loci are sorted into gametes independently of one another

Prop. recombinants = recombinant individuals / total

Crossing true-breeding (homozygous) round (RR) with wrinkled (rr) peas, Mendel first obtained a population of exclusively round (Rr) individuals

selection and genetic drift

The concept of tracing gene genealogies backwards in time is the basis of coalescent theory, a retrospective stochastic model describing the effects of genetic drift.

G’ = 1/N + (1-(1/N))G

= G + 1/N (1 - G)

(1-G) = H

defined as the number of all mutations that arise in a population times the probability that any of those mutations is fixed. If the mutation rate per site and generation is u, 2Nu mutations will arise every generation at the site. We thus have

k = (2N u) • (1/2N) = u

To obtain the TMRCA we can simply sum up the waiting times for all coalescent events. This is equivalent to the total height of the tree

Ploidy: change in the number of whole sets of chromosomes (aneuploidy, e.g. Trisomy 21 in humans) or even all chromosomes of a genome (polyploidization in maize)