Lecture_12_molecular evolution 2008_Ally.ppt

Editor's Notes

• #1: Molecular evolution encompasses two areas of study: The evolution of macromolecules: the rates and patterns of change in the genetic material (DNA sequences) and in the encoded products proteins The evolutionary history of genes and organisms
• #3: This field has its roots in two separate disciplines: population genetics and molecular biology. Population genetics provides the theoretical background and molecular biology provides the empirical data. The first complete sequence of a protein (insulin) was determined in 1952 by F.Sanger and colleagues.
• #6: Here are some sequences taken from Arabidopsis thaliana – two individuals 145 and 134. These are the MADS BOX genes important for flower development. On the left is the identifier =name of gene, species, individual Bolded in black is the reference individual. We will compare this sequence to the others. Btwn AgAt145 and AgAt134 we have two changes in the third position. Both are synonymous change because the amino acid stay the same. The first is a transitions because G->A (a change from one purine to another) but the second case G->C (from purine to pyrimidine to another) is an example of a transversion. Comparing AgAt145 to Sep1134 and Sep1145 A->G (a transition) and T->G (a transversion) but this time lysine changes to arginine in the first and in the second case leucine changes to valine both are nonsynonymous changes because they result in the amino acid changing. Comparing AgAt145 to CalAt145 and CalAt134: we see there is the deletion of a codon creating a gap. But there is also a change from G->T (transversion) resulting in a nonsynonymous change = valine changes to phenylalanine.
• #7: Mutations occur-sometimes they are the result of DNA replication errors or errors in DNA repair leading to the changes in nucleotides, however, sometimes the changes are larger creating deletions and insertions. When we ask the question HOW and WHY have molecular sequences evolved the way they do? We are really interested in knowing once a mutation arises what happens to it? Does it remain in the population as one of several mutant alleles? In which case we consider this a polymorphism. If on the other hand it fixes in a population, then the change is considered a subsitution.
• #8: At the start, time 0 generation, everyone in the population is aaat. As time passes a mutation arises in individual 5. Now there are two different sequences segregating in the population = polymorphism. This polymorphism is present in several individuals within the population and hangs around for generations 10 to about 29. Finally in generation 30 it is fixed – every individual in the population has a “c” at this second nt. This is the same as the frequency of p reaching 1. Again in generation 40, a new mutation arises and we have a polymorphism again.
• #9: Any mutation that happens on a red branch will appear as a polymorphism within species one
• #10: Here the phylogeny is divided into two parts: between species branches and within species branches. Within species branches connect all the alleles within each species to their most recent common ancestor. Between species branches connect these common ancestors to the common ancestor of the whole phylogeny. A mutation on a between species branch will appear in all the descendant alleles and thus will be a fixed difference between species. A mutation on a within species branch will be a polymorphism within a species
• #13: A new mutant arising as a single copy in a diploid population of size N has an initial frequency of 1/2N. If only drift is acting what is the probability of fixation for that neutral allele? 1/2N
• #14: Probability of fixation of an advantageous allele * the number of new mutants arising every generation. Probability of fixation for positive values of s when N is large, is 2s. IF the absolute value of s is small the probability of fixation is 2s/1-exp(-4Ns)
• #15: These last two results are noteworthy because it means advantageous mutations don’t always fix in a population. In the case of an advantageous mutation with s=0.01, the probability it will fix is 2% but that also means 98% of all the mutations with the selective advantage of 0.01 are lost. On the other hand, even slightly deleterious mutations have a finite (albeit small) chance of fixing in a population.
• #18: The 1960s witnessed a revolution in population genetics. With the introduction of electrophoresis into popgen studies, soon led to the discovery of large amounts of genetic variability in natural populations such as humans and Drosophila. In 1968 Kimura postulated that the majority of the molecular changes in evolution were due to the random fixation of neutral or nearly neutral mutations. This created a dispute between neutralists and selectionist. The dispute essentially concerns the distribution of fitness values of mutant alleles.
• #20: From this table, it is clear that the rate of nonsynonymous substitution is variable among different genes, ranging from zero to about 2x10-9 substitutions per nonsynonymous site per year Histones have an unusually low replacement substitution rate. Look at the column describing the rate of synonymous substitution. It also varies though not as much as the rate of nonsynonymous substittuion
• #22: Looking at H3 and H4 it is clear there is some interaction with both the DNA and other histones
• #24: From this table, it is clear that the rate of nonsynonymous substitution is variable among different genes, ranging from zero to about 2x10-9 substitutions per nonsynonymous site per year Histones have an unusually low replacement substitution rate. Look at the column describing the rate of synonymous substitution. It also varies though not as much as the rate of nonsynonymous substittuion
• #25: Immunoglobin genes are proteins found in the blood or bodily fluids of vertebrates and are used by the immune system to identify and neutral foreign objects. It is the small region at the tip of the protein that is extremely variable. Each variant can bind a different target or antigen. A huge diversity in this region allows the immune system to recognize an equally wide diversity of antigens
• #26: Immunoglobin genes are proteins found in the blood or bodily fluids of vertebrates and are used by the immune system to identify and neutral foreign objects. It is the small region at the tip of the protein that is extremely variable. Each variant can bind a different target or antigen. A huge diversity in this region allows the immune system to recognize an equally wide diversity of antigens
• #28: Probability of fixation of an advantageous allele * the number of new mutants arising every generation. Probability of fixation for positive values of s when N is large, is 2s. IF the absolue value of s is small the probability of fixation is 2s/1-exp(-4Ns)
• #35: Any mutation that happens on a red branch will appear as a polymorphism within species one
• #36: Here the phylogeny is divided into two parts: between species branches and within species branches. Within species branches connect all the alleles within each species to their most recent common ancestor. Between species branches connect these common ancestors to the common ancestor of the whole phylogeny. A mutation on a between species branch will appear in all the descendant alleles and thus will be a fixed difference between species. A mutation on a within species branch will be a polymorphism within a species
• #38: Remember we’ve divided nt subsitutions in a coding region into two types: replacement (non-synonymous) and synonymous. For a particular phylogeny and mutation rate, if mutations occur randomly over time and if the chance that a mutation does or doesn’t cause a change in the amino acid remains constant, then ratio of the replacement changes to silent changes should be the same along any of these branches.
• #39: Remember we’ve divided nt subsitutions in a coding region into two types: replacement (non-synonymous) and synonymous. For a particular phylogeny and mutation rate, if mutations occur randomly over time and if the chance that a mutation does or doesn’t cause a change in the amino acid remains constant, then ratio of the replacement changes to silent changes should be the same along any of these branches.