Chapter 3Chapter 3Substitution PatternsSubstitution Patterns

Presented by:Presented by:

Adrian PadillaAdrian Padilla

OverviewOverview

Patterns of Substitutions within Patterns of Substitutions within GenesGenes• Mutation ratesMutation rates• Functional constraintFunctional constraint• Synonymous vs. Nonsynonymous Synonymous vs. Nonsynonymous

substitutionssubstitutions• Indels and pseudogenesIndels and pseudogenes• Substitutions vs. mutationsSubstitutions vs. mutations• FixationFixation

OverviewOverview

Estimating Substitution NumbersEstimating Substitution Numbers• Jukes-Cantor ModelJukes-Cantor Model

Variations in Evolutionary Rates Variations in Evolutionary Rates between Genesbetween Genes

Evolution in OrganellesEvolution in Organelles

MutationsMutations

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

Mutation RatesMutation Rates

Rate of substitution (Rate of substitution (r)r) • rr = K/(2T) = K/(2T)

K is expressed in terms of the number of K is expressed in terms of the number of substitutions per sitesubstitutions per site

T is TimeT is Time

Substitution rates can give insight into the Substitution rates can give insight into the dates of evolutionary events for which no dates of evolutionary events for which no other physical evidence is available.other physical evidence is available.

Functional ConstraintFunctional Constraint

Natural selectionNatural selection – Differential success – Differential success between individuals in passing on genes to between individuals in passing on genes to subsequent generations due to differences subsequent generations due to differences in fitnessin fitness• Advantageous, disadvantageous, neutral Advantageous, disadvantageous, neutral

mutationsmutations

Functional constraintFunctional constraint – The tendency in – The tendency in particularly important genes to particularly important genes to accumulate changes very slowly over the accumulate changes very slowly over the course of evolutioncourse of evolution

Synonymous vs. Nonsynonymous Synonymous vs. Nonsynonymous SubstitutionSubstitution

Synonymous SubstitutionSynonymous Substitution - Change at - Change at the nucleotide level of coding the nucleotide level of coding sequences that does not change the sequences that does not change the amino acid sequence of the protein.amino acid sequence of the protein.

Nonsynonymous SubstitutionNonsynonymous Substitution – Any – Any nucleotide substitution that alters a nucleotide substitution that alters a codon to one for a different amino codon to one for a different amino acid.acid.

Synonymous vs. Nonsynonymous Synonymous vs. Nonsynonymous SubstitutionSubstitution

Nondegenerate sitesNondegenerate sites – Codon positions where – Codon positions where mutations always result in amino acid mutations always result in amino acid substitutions.substitutions.

Twofold degenerate sitesTwofold degenerate sites – Codon postitions – Codon postitions where two different nucleotides result in the where two different nucleotides result in the translation of the same amino acid, but the two translation of the same amino acid, but the two other nucleotides code for a different amino acid.other nucleotides code for a different amino acid.

Fourfold degenerate sitesFourfold degenerate sites – Codon position where – Codon position where changing a nucleotide to any of the three changing a nucleotide to any of the three alternatives has no effect on the amino acid that alternatives has no effect on the amino acid that ribosomes insert into proteinsribosomes insert into proteins

Indels and PseudogenesIndels and Pseudogenes

IndelsIndels – Insertion and deletion – Insertion and deletion mutations for DNA replication.mutations for DNA replication.• Mutations change the gene to give it a Mutations change the gene to give it a

new function that effects the fitness of new function that effects the fitness of the organism.the organism.

PseudogenePseudogene - Acquires mutations - Acquires mutations that make it nonfunctional and that make it nonfunctional and transcriptionally inactive.transcriptionally inactive.

Mutations vs. SubstitutionsMutations vs. Substitutions

MutationsMutations – any change in nucleotide – any change in nucleotide sequence that occur due to mistakes sequence that occur due to mistakes in DNA replication or repair.in DNA replication or repair.

SubstitutionSubstitution – changes that evolution – changes that evolution has tolerated.has tolerated.

FixationFixation

AllelesAlleles – Different versions of any – Different versions of any given gene within a species of given gene within a species of organism.organism.

FixationFixation – A condition in which an – A condition in which an allele’s frequency within a population allele’s frequency within a population reaches 100%.reaches 100%.

FixationFixation

New alleles arise from mutations New alleles arise from mutations occurring to an existing allele within a occurring to an existing allele within a single member of a population.single member of a population.

As a result new versions of genes typically As a result new versions of genes typically begin at very low frequencies (q).begin at very low frequencies (q).• q = 1/2Nq = 1/2N• N is the number of reproductively active diploid N is the number of reproductively active diploid

organisms within the population.organisms within the population.

FixationFixation

Mutations that make organisms less likely Mutations that make organisms less likely to survive and reproduce tend to be to survive and reproduce tend to be removed from the gene pool through the removed from the gene pool through the process of natural selection and their process of natural selection and their frequencies eventually return to 0.frequencies eventually return to 0.

When advantageous alleles do arise, their When advantageous alleles do arise, their frequencies should move progressively frequencies should move progressively toward 1.toward 1.

FixationFixation Selectively neutralSelectively neutral – or neutral mutation – or neutral mutation

that has no effect on the fitness of an that has no effect on the fitness of an organism.organism.

The probability (P) that the neutral variant The probability (P) that the neutral variant of a gene will eventually be lost from the of a gene will eventually be lost from the population is:population is:• P = 1 – q (frequency)P = 1 – q (frequency)

The probability that the neutral allele will The probability that the neutral allele will be fixed is equal to q.be fixed is equal to q.

FixationFixation

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

Jukes-Cantor ModelJukes-Cantor Model Assumes that each Assumes that each

nucleotide is just as nucleotide is just as likely to change into likely to change into any other nucleotide any other nucleotide at rateat rate..

PPC(C(t)t)= = 1/4 + (3/4)1/4 + (3/4)ee-4-4tt

• Probability you end up at C Probability you end up at C when starting at C for a when starting at C for a period of time (period of time (t).t).

More substitutions than More substitutions than observed substitutions.observed substitutions.

Transitions and TransversionsTransitions and Transversions PurinePurine – nitrogenous bases that have a two-ring – nitrogenous bases that have a two-ring

structure. (Guanine and Adenine)structure. (Guanine and Adenine)

PyrimidinePyrimidine – nitrogenous bases with only a one- – nitrogenous bases with only a one-ring structure. (Cytocine and Thymine)ring structure. (Cytocine and Thymine)

TransitionsTransitions – The exchange of one purine for – The exchange of one purine for another or exchangeing one pyrimidine for another or exchangeing one pyrimidine for anotheranother

TransversionsTransversions – The exchange of a purine for a – The exchange of a purine for a pyrimidine or vice versa.pyrimidine or vice versa.

Evolutionary RateEvolutionary Rate

Evolutionary rateEvolutionary rate – is the rate at – is the rate at which something has changed.which something has changed.

• Two factorsTwo factors1.1. Differences in mutation frequency.Differences in mutation frequency.2.2. The extent to which natural selection The extent to which natural selection

affects the organism.affects the organism.

Evolutionary pressureEvolutionary pressure – Pressure – Pressure natural selection puts on the gene natural selection puts on the gene to survive.to survive.

Evolution in OrganellesEvolution in Organelles

Mitochondrial DNA (mtDNA) has a 10-fold Mitochondrial DNA (mtDNA) has a 10-fold higher rate of mutations than that found in higher rate of mutations than that found in nuclear DNA.nuclear DNA.

Higher rate of both synonymous and Higher rate of both synonymous and nonsynonymous substitutions in mtDNA.nonsynonymous substitutions in mtDNA.

Comparisons of mtDNA are often used to Comparisons of mtDNA are often used to study relationships between closely study relationships between closely related polpulations of organisms.related polpulations of organisms.

SummarySummary Mutation is when there is a change in information Mutation is when there is a change in information

content of a DNA molecule due to replication content of a DNA molecule due to replication error or damage.error or damage.

Mutations do not affect the fitness of an organism Mutations do not affect the fitness of an organism to the same degree.to the same degree.

Natural selection causes many to be lost from the Natural selection causes many to be lost from the gene pool and the changes that remain are gene pool and the changes that remain are referred to as substitutions. referred to as substitutions.

Substitution rates can be used to measure the Substitution rates can be used to measure the functional importance of a gene.functional importance of a gene.