ÌÇÐÄAPP

Meeting of Genetic & of Evolutionary Thought: Mendel's Century

1900: Mendel Re-discovered but
        Mendelians versus Biometricians [W Bateson versus K Pearson]
                Discrete versus Continuous variation

        Math-challenged biologists: T Hardy (1908) sets null hypothesis
        TH Morgan [1866 - 1945] Drosophila experiments (1910 - ) [Nobel,1936]
                    Genes occur in linear order on Chromosomes

        RA Fisher [1890 - 1962] Genetical Theory of Natural Selection (1930)
                Natural Selection consistent with Mendelian genetics
         S Wright [1889 - 1988] Evolution in Mendelian Populations (1931)
                Moderating factors in evolution: mutation, migration, inbreeding, genetic drift
                  S Wright HM Slatis  SM Carr  etc
                 L Pauling  A Pardee [PaJaMo exp] AC Wilson   SM Carr etc

The Modern Synthesis (1940s ~ 1960s)
        Th Dobzhansky [1900 - 1975] Genetics and the Origin of Species (1937; 4th ed. 1970)
                "Evolution is the change in genetic composition of populations"
                Demonstrations of selection in natural populations (Drosophila)
        E Mayr [1904 - 2005] Systematics and the Origin of Species (1942)
                Allopatric speciation; Biological Species Concept
                Relationships as basis of taxonomy [incompletely applied]
                 Animal Species & Evolution (1963) capstone of Synthesis
        GG Simpson  [1902 - 1984] Tempo & Mode in Evolution (1944)
                Rates & patterns inferred from fossil record; Evolutionary Species Concept
                Relationships in time supersede ecological differences in space
         GL Stebbins [1906 - 2000] Variation and Evolution in Plants (1950)
                Plant evolution analogous to animal evolution
                Flowering Plants: Evolution Above the Species Level (1974)

        =>  Natural Selection acting on single genes explains trans-specific evolution
                  Evolution proceeds slowly & gradually
                  Microevolution explains Macroevolution:
                        species variation continuous with generic differences, & so on

Challenges to the Synthesis (>1966)
        Variation assumed low: Classical versus Balanced schools
                HJ Muller:     Heterozygosity: H < 0.001
                B Wallace:    H = 0.01 ~ 0.10
        Phylogenetic Systematics replaces Evolutionary Systematics: logical consistency
        N Eldredge & [1941 - 2002]: Punctuated Equilibria in fossil record ?
                Process inferred from Pattern?

Molecular Biology revives Evolution
        DNA as transforming substance (1944) (Huh?)
         DNA structure (1953) (Yawn)
        Genetic Code complete (1965) (Oh?)
         Sickle Cell Anemia recognized as (Linus Pauling et al. 1949)
         Protein Electrophoresis (1966) in Drosophila, Homo shows extensive variation
                 ***Rapid proliferation of protein variation ("allozyme") studies
                    Lots of variation: is it important ?
                    Neutralist versus Selectionist argument
            AC Wilson & VM Sarich: Molecular Clock (1967)
                    & MC King: Chimp x Human allozymes:  3~5 MYA (!?!) separation,
                                        98.6% = '99%' similar (1975): (!?!)
                    & R Cann & M Stoneking on the recent human "mitochondrial Eve"
                    & S ±Êää²ú´Ç on ancient DNA (aDNA) (Nobel Prize, 2022)
                    Gene regulation >> change in allelic composition

DNA in ascendancy
        Restriction Fragment Length Polymorphism: RFLPs ("riff lips") of mtDNA
            Restriction Enzymes (Nobel Prize, 1978) cut DNA at specific points
            ***Rapid proliferation of within & among species mtDNA RFLP map studies (1979)
            "Out of Africa" hypothesis supported by from RFLP maps of human mtDNA (1987)

        "Sanger" sequencing (1977) method of choice for 40 years (F Sanger: 2nd Nobel Prize, 1980)
            of phage φX174 (5,386 bp)
            Human mtDNA "Anderson sequence" (1981); reworked as rCRS: 16,569 bp (1999)

        DNA Fingerprinting described; forensic applications follow immediately (1985) (A Jeffreys)
            ***Rapid proliferation of microsatellite nucDNA studies

        Polymerase Chain Reaction announced, automated (K Mullis, Nobel Prize 1993)
            ***Rapid proliferation of within & among species DNA sequence studies
            Ape & Human mtDNA genomes compared (1995)

        ABI Automated DNA Sequencer (1986)
            Technical developments speed HuGO: "Next-Gen" sequencing
            (1990): implications of Big Machine Biology (, 1997)
                Complete E. coil genome sequenced: 4.6 Mbp (1997)

21st Century: Too Much Information
    (1983 - ): 2,000 sequences 213.2 Gb (June 2016) [HOMEWORK: How many in Sept 2026?]
            [Release 59, March 1989: 26.3 Mb on 28 5.25" floppies]
            "Draft" human heterochromatic genome (2001); "Finished" 3 Gbp (2003)
            *** Human Genome established fact: annotate, interpret, manipulate, etc. ***
            "NextGen" DNA sequencing demonstrated (2002), routine from 2012
                Ex.: Illumina Sequencing platform
                            >>106 nucleotides / second
                            ~1 human genome (1x coverage) / hour
                            ~1 human genome (30X coverage) / day "finished"
                Ex.: (1KGP) announced (2008)
                            Comparative data on major human continental groups
                Ex.: Environmental Sequencing monitors micro-organisms (2004)
                            1,500 L seawater 1.2M "DNA segments" in 1 Gbp
                            DNA identified to major taxon: major microbial "ecosystem" shifts recognizable

    *** Waaay too much data: Bioinformatics essential to 21st century Biologist

HOMEWORK: A standard meme of pedigree analysis in introductory Genetics classes is the inheritance of the novel Hemophilia A allele mutation in Britain's Queen Victoria to her descendants, and in the royal houses of Europe.
                        Consider Queen Victoria's pedigree for (a) Hemophilia A in the bi-parental nuclear genome (nucDNA), (b) female-inherited mitochondrial genome (mtDNA), and (c) the male-restricted yDNA in her consort Prince Albert , or Prince Philip, Duke of Edinburgh.
                       The patterns are quite different: explain why. Identify those individuals with any pairwise or three-way combination of the three genotypes. What genetic characteristics drive this?
Text material © 2026 by Steven M. C