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Lecture 3

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Department
Biochemistry
Course
BCH447H1
Professor
Larry Moran
Semester
Spring

Description
BCH 447 lecture 3 notes Natural selection is much more likely to dominate in a large population than a small population because in a small population the chances are higher for a gene to be lost and not fixed. Drift competes with selection. All mutations have to survive the first initial stage. When they are first provided to one individual. Regardless of small or large. But the chance of something being lost through random genetic drift is the same in initiall stages but decreases over time in a larger population. Regardless of the population size, the beneficial mutation must reach a certain threshold before it is immune to loss. This threshold is higher in a smaller population. Natural selection is actually favoured in larger populations and disfavoured in smaller ones. Genetic drift is more likely to cause loss of a beneficial mutation in small populations and less likely to do the same in larger ones. This does not mean that drift doesn't happen in population. The reasoning why natural selection predominates in large populations is because there is such a high concentration of mutation in large populations. So the rate of fixation of genetic drift will be the same regardless of population. So, small populations lose have few mutations and therefore few mutations are lost Large populations have many mutations and many mutations are lost. But because they have so many mutations the likelihood of one being fixed is higher. The number of mutations increases with a larger population size. And therefore there are more mutations in large populations... As such there is a larger likelihood that one gets fixed. The reason we see a molecular clock for all organisms is because the rate of substitution of amino acids is the same in both lineages independent of population size. For various lineages the rate of evolution is relatively constant over time. We picked up the 1963 margoliash paper: Side note, horizon thresholds.. It's a look back time. The further back we go the scale of remembering shortness. We can't distinguish between 10000 and 1000 years ago. 1963 is well remembered by our proff. Lol Back to 1963: Homologus is defined as descent from a common ancestor. When proteins are homologous it means that they are evolutionarily related. This is a strict definition. Proteins with the same function may or may not be homologous... An example of same function but non homologous is different actions in the citric acid cycle are carried out by enzymes that are completely unrelated to each other. These are examples of convergence into similar functions but non homologous. The tricky part comes when we have intermediate commonalities. The cutoff for homology is. Homology has been used as a problem for evolution... We are saying that these two proteins descend from a common ancestor, therefore that's proof that they descend from a common ancestor. This is not the argument science makes. We say, these proteins are really similar in genetics... They are homologous, therefore it is likely that they descended from a common source. It is not a problem. homology is a conclusion based on similarity. Margoliash says... Homology is a function of similarity. And our cutoff for homology is around 20%. Anything below that... It could've been chance. 20% is the twilight zone. Homology is an all or none situation. Things are either homologous or aren't homologous. Nothing is 50% homologous. Things are 50% similar. The data is similarity the conclusion is homology. In areas where the heme group is attached to cytochrome C there are no changes in amino acid sequences. All the proteins have the same amino acid sequence. These guys are conserved because of function, we don't mutate them because they are likely lethal. If mutations are lethal we won't see them exist... Very important point. The only plausible explanation for sequence homology is because the individual genes must be related. They must descend from a common ancestor and changed over time. This is why a tree can be formed. Thus there is little doubt that the cytochrome C's are homologous to each other. Margoliash and the amino acid sequencing of cytochrome c showed evidence for relationships between organisms. In 1963 there was no genetic code. note, that in every position of a protein we will not find every possible amino acid. But the reasoning behind it is not that the amino acid didn't mutate to whatever it wants. It just means whatever had that mutation died. This is why there is conservation even in mutation... Ex, important hydrophobic or hydrophilic sectors tend to remain as such. There are two possibilities for conservation of sequence. It's either that only a certain subset of amino acids can replace a certain protein sector because it would be detrimental. Or... There is biase in mutation... Such that mutations prefer to mutate to common amino acids, ex... Luecine to isoleucine. The truth is explained above the above paragraph. Interestingly in contrast to the logic that any mutation can occur but some will cause death and are therefore not seen. It seems that there are in non function
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