BIOE 109 Summer 2009 Lecture 6- Part II Molecular evolution

The mechanism of inheritance circa 1865: Mendel’s work demonstrates “factors” in pea plants that are inherited independently from one another. circa 1900: rediscovery of Mendel’s work : TH Morgan inferred existence of “genes” and mapped their locations on chromosomes

“Classical” versus “balanced” views of genome structure

“Classical” versus “balanced” views of genome structure controversy began in the 1920’s with the establishment of two schools of genetics.

“Classical” versus “balanced” views of genome structure controversy began in the 1920’s with the establishment of two schools of genetics. the “Naturalists” studied natural populations (e.g. Dobzhansky, Mayr).

“Classical” versus “balanced” views of genome structure controversy began in the 1920’s with the establishment of two schools of genetics. the “Naturalists” studied natural populations (e.g. Dobzhansky, Mayr). the “Mendelians” studied genetics exclusively in the laboratory (e.g., Morgan, Sturtevant, Muller).

Classical

Classical = “wild type” allele - = deleterious recessive allele

Classical Balanced A 1 B 2 C 1 D 4 E 3 F 6 A 3 B 2 C 4 D 5 E = “wild type” allele - = deleterious recessive allele

Classical Balanced A 1 B 2 C 1 D 4 E 3 F 6 A 3 B 2 C 4 D 5 E 5 - Most loci homozygous Most loci heterozygous for wild type alleles

Classical Balanced A 1 B 2 C 1 D 4 E 3 F 6 A 3 B 2 C 4 D 5 E 5 - Most loci homozygous Most loci heterozygous for wild type alleles Polymorphism rare Polymorphism common

Why is this distinction important? Classical Balanced

Why is this distinction important? Classical Balanced SpeciationDifficult Easy (mutation- (opportunity- limited) limited)

Why is this distinction important? Classical Balanced SpeciationDifficult Easy (mutation- (opportunity- limited) limited) SelectionPurifying Balancing

Why is this distinction important? Classical Balanced SpeciationDifficult Easy (mutation- (opportunity- limited) limited) SelectionPurifying Balancing PopulationInter > Intra Intra > Inter variation

Why is this distinction important? Classical Balanced SpeciationDifficult Easy (mutation- (opportunity- limited) limited) SelectionPurifying Balancing PopulationInter > Intra Intra > Inter variation Polymorphismtransient balanced (short-lived) (long-lived)

Allozyme electrophoresis setup

Starch gel stained for Phosphoglucomutase (Pgm)

Extensive allozyme variation exists in nature Vertebrates (648 species)

Extensive allozyme variation exists in nature… …so this confirms the balanced view? Vertebrates (648 species)

Extensive allozyme variation exists in nature… …so this confirms the balanced view? Vertebrates (648 species) NO! MOST POLYMORPHISMS ARE NEUTRAL!

The neutral theory of molecular evolution first proposed by Motoo Kimura in 1968.

The neutral theory of molecular evolution first proposed by Motoo Kimura in two observations led Kimura to develop neutral theory:

The neutral theory of molecular evolution first proposed by Motoo Kimura in two observations led Kimura to develop neutral theory: 1.“Excessive” amounts of protein (allozyme) polymorphism 2.Molecular clock

2. The molecular clock first reported by Zuckerkandl and Pauling in 1962.

2. The molecular clock first reported by Zuckerkandl and Pauling in 1962.

2. The molecular clock first reported by Zuckerkandl and Pauling in Age 7 Age 17 Age 22 Age 46

2. The molecular clock first reported by Zuckerkandl and Pauling in refers to apparent constant rate of protein evolution over large periods of time.

2. The molecular clock first reported by Zuckerkandl and Pauling in Method:

2. The molecular clock first reported by Zuckerkandl and Pauling in Method: 1. Obtain homologous amino acid sequences from a group of taxa.

2. The molecular clock first reported by Zuckerkandl and Pauling in Method: 1. Obtain homologous amino acid sequences from a group of taxa. 2. Estimate divergence times (from the fossil record).

2. The molecular clock first reported by Zuckerkandl and Pauling in Method: 1. Obtain homologous amino acid sequences from a group of taxa. 2. Estimate divergence times (from the fossil record). 3. Assess relationship between protein divergence and evolutionary time.

Time (millions of years) No. of amino acid substitutions The molecular clock  -globin gene in vertebrates

The molecular clock ticks at different rates for silent and replacement mutations

Kimura argued that the molecular clock reflects the action of random drift, not selection! Time (millions of years) No. of amino acid substitutions  -globin gene in vertebrates

Main features of the neutral theory 1. The rate of protein evolution is roughly constant per site per year.

Main features of the neutral theory 1. The rate of protein evolution is roughly constant per site per year. - this is the "molecular clock" hypothesis.

Main features of the neutral theory 1. The rate of protein evolution is roughly constant per site per year. - this is the "molecular clock" hypothesis. - per site PER YEAR, not per site PER GENERATION Shorter generation time faster rate of molecular evolution Longer generation timeslower rate of molecular evolution

2. Rate of substitution of neutral alleles equals the mutation rate to neutral alleles.

2. Rate of substitution of neutral alleles equals the mutation rate to neutral alleles. this rate is unaffected by population size!

3. Rates of protein evolution vary with degree of selective constraint.

3. Rates of protein evolution vary with degree of selective constraint. “selective constraint” represents the ability of a protein to “tolerate” random mutations.

3. Rates of protein evolution vary with degree of selective constraint. “selective constraint” represents the ability of a protein to “tolerate” random mutations. for highly constrained molecules, most mutations are deleterious and few are neutral.

3. Rates of protein evolution vary with degree of selective constraint. “selective constraint” represents the ability of a protein to “tolerate” random mutations. for highly constrained molecules, most mutations are deleterious and few are neutral. for weakly constrained molecules, more mutations are neutral and few are deleterious.

Time (millions of years) No. of amino acid substitions  -globin histone H4 Degree of constraint dictates rate of evolution

high constraint  low   slow rate of evolution

low constraint  high   fast rate of evolution