1. Chapter 3 Substitution Patterns Presented by: Adrian Padilla

2. Overview Patterns of Substitutions within Genes Patterns of Substitutions within Genes Mutation ratesMutation rates Functional constraintFunctional constraint Synonymous vs. Nonsynonymous substitutionsSynonymous vs. Nonsynonymous substitutions Indels and pseudogenesIndels and pseudogenes Substitutions vs. mutationsSubstitutions vs. mutations FixationFixation

3. Overview Estimating Substitution Numbers Estimating Substitution Numbers Jukes-Cantor ModelJukes-Cantor Model Variations in Evolutionary Rates between Genes Variations in Evolutionary Rates between Genes Evolution in Organelles Evolution in Organelles

4. Mutations Mutation- Change in a nucleotide sequence that occurs due to mistakes in DNA replication or repair process. Mutation- Change in a nucleotide sequence that occurs due to mistakes in DNA replication or repair process. Deleterious (disadvantageous)Deleterious (disadvantageous) AdvantageousAdvantageous neutralneutral

5. Mutation Rates Rate of substitution (r) Rate of substitution (r) r = K/(2T)r = K/(2T) K is expressed in terms of the number of substitutions per site K is expressed in terms of the number of substitutions per site T is Time T is Time Substitution rates can give insight into the dates of evolutionary events for which no other physical evidence is available. Substitution rates can give insight into the dates of evolutionary events for which no other physical evidence is available.

6. Functional Constraint Natural selection – Differential success between individuals in passing on genes to subsequent generations due to differences in fitness Natural selection – Differential success between individuals in passing on genes to subsequent generations due to differences in fitness Advantageous, disadvantageous, neutral mutationsAdvantageous, disadvantageous, neutral mutations Functional constraint – The tendency in particularly important genes to accumulate changes very slowly over the course of evolution Functional constraint – The tendency in particularly important genes to accumulate changes very slowly over the course of evolution

8. Synonymous vs. Nonsynonymous Substitution Synonymous Substitution - Change at the nucleotide level of coding sequences that does not change the amino acid sequence of the protein. Synonymous Substitution - Change at the nucleotide level of coding sequences that does not change the amino acid sequence of the protein. Nonsynonymous Substitution – Any nucleotide substitution that alters a codon to one for a different amino acid. Nonsynonymous Substitution – Any nucleotide substitution that alters a codon to one for a different amino acid.

9. Synonymous vs. Nonsynonymous Substitution Nondegenerate sites – Codon positions where mutations always result in amino acid substitutions. Nondegenerate sites – Codon positions where mutations always result in amino acid substitutions. Twofold degenerate sites – Codon postitions where two different nucleotides result in the translation of the same amino acid, but the two other nucleotides code for a different amino acid. Twofold degenerate sites – Codon postitions where two different nucleotides result in the translation of the same amino acid, but the two other nucleotides code for a different amino acid. Fourfold degenerate sites – Codon position where changing a nucleotide to any of the three alternatives has no effect on the amino acid that ribosomes insert into proteins Fourfold degenerate sites – Codon position where changing a nucleotide to any of the three alternatives has no effect on the amino acid that ribosomes insert into proteins

10. Indels and Pseudogenes Indels – Insertion and deletion mutations for DNA replication. Indels – Insertion and deletion mutations for DNA replication. Mutations change the gene to give it a new function that effects the fitness of the organism.Mutations change the gene to give it a new function that effects the fitness of the organism. Pseudogene - Acquires mutations that make it nonfunctional and transcriptionally inactive. Pseudogene - Acquires mutations that make it nonfunctional and transcriptionally inactive.

11. Mutations vs. Substitutions Mutations – any change in nucleotide sequence that occur due to mistakes in DNA replication or repair. Mutations – any change in nucleotide sequence that occur due to mistakes in DNA replication or repair. Substitution – changes that evolution has tolerated. Substitution – changes that evolution has tolerated.

12. Fixation Alleles – Different versions of any given gene within a species of organism. Alleles – Different versions of any given gene within a species of organism. Fixation – A condition in which an allele’s frequency within a population reaches 100%. Fixation – A condition in which an allele’s frequency within a population reaches 100%.

13. Fixation New alleles arise from mutations occurring to an existing allele within a single member of a population. New alleles arise from mutations occurring to an existing allele within a single member of a population. As a result new versions of genes typically begin at very low frequencies (q). As a result new versions of genes typically begin at very low frequencies (q). q = 1/2Nq = 1/2N N is the number of reproductively active diploid organisms within the population.N is the number of reproductively active diploid organisms within the population.

14. Fixation Mutations that make organisms less likely to survive and reproduce tend to be removed from the gene pool through the process of natural selection and their frequencies eventually return to 0. Mutations that make organisms less likely to survive and reproduce tend to be removed from the gene pool through the process of natural selection and their frequencies eventually return to 0. When advantageous alleles do arise, their frequencies should move progressively toward 1. When advantageous alleles do arise, their frequencies should move progressively toward 1.

15. Fixation Selectively neutral – or neutral mutation that has no effect on the fitness of an organism. Selectively neutral – or neutral mutation that has no effect on the fitness of an organism. The probability (P) that the neutral variant of a gene will eventually be lost from the population is: The probability (P) that the neutral variant of a gene will eventually be lost from the population is: P = 1 – q (frequency)P = 1 – q (frequency) The probability that the neutral allele will be fixed is equal to q. The probability that the neutral allele will be fixed is equal to q.

16. Fixation Saturation mutagenesis – when molecular biologists make all possible changes to the nucleotide sequence of a gene to determine which alter its function. Saturation mutagenesis – when molecular biologists make all possible changes to the nucleotide sequence of a gene to determine which alter its function.

17. Jukes-Cantor Model Assumes that each nucleotide is just as likely to change into any other nucleotide at rate. Assumes that each nucleotide is just as likely to change into any other nucleotide at rate. P C(t) = 1/4 + (3/4)e -4t P C(t) = 1/4 + (3/4)e -4t Probability you end up at C when starting at C for a period of time (t).Probability you end up at C when starting at C for a period of time (t). More substitutions than observed substitutions. More substitutions than observed substitutions.

18. Transitions and Transversions Purine – nitrogenous bases that have a two-ring structure. (Guanine and Adenine) Purine – nitrogenous bases that have a two-ring structure. (Guanine and Adenine) Pyrimidine – nitrogenous bases with only a one- ring structure. (Cytocine and Thymine) Pyrimidine – nitrogenous bases with only a one- ring structure. (Cytocine and Thymine) Transitions – The exchange of one purine for another or exchangeing one pyrimidine for another Transitions – The exchange of one purine for another or exchangeing one pyrimidine for another Transversions – The exchange of a purine for a pyrimidine or vice versa. Transversions – The exchange of a purine for a pyrimidine or vice versa.

19. Evolutionary Rate Evolutionary rate – is the rate at which something has changed. Evolutionary rate – is the rate at which something has changed. Two factorsTwo factors 1. Differences in mutation frequency. 2. The extent to which natural selection affects the organism. Evolutionary pressure – Pressure natural selection puts on the gene to survive. Evolutionary pressure – Pressure natural selection puts on the gene to survive.

20. Evolution in Organelles Mitochondrial DNA (mtDNA) has a 10-fold higher rate of mutations than that found in nuclear DNA. Mitochondrial DNA (mtDNA) has a 10-fold higher rate of mutations than that found in nuclear DNA. Higher rate of both synonymous and nonsynonymous substitutions in mtDNA. Higher rate of both synonymous and nonsynonymous substitutions in mtDNA. Comparisons of mtDNA are often used to study relationships between closely related polpulations of organisms. Comparisons of mtDNA are often used to study relationships between closely related polpulations of organisms.

21. Summary Mutation is when there is a change in information content of a DNA molecule due to replication error or damage. Mutation is when there is a change in information content of a DNA molecule due to replication error or damage. Mutations do not affect the fitness of an organism to the same degree. Mutations do not affect the fitness of an organism to the same degree. Natural selection causes many to be lost from the gene pool and the changes that remain are referred to as substitutions. Natural selection causes many to be lost from the gene pool and the changes that remain are referred to as substitutions. Substitution rates can be used to measure the functional importance of a gene. Substitution rates can be used to measure the functional importance of a gene.