Mendel's Century

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 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)
        Molecular Biology not integrated into Synthesis
        Variation assumed low: Classical versus Balanced schools
                HJ Muller:     Heterozygosity: H ~ 0.001
                B Wallace:    H ~ 1.000
        Phylogenetic replaces Evolutionary Systematics: logical consistency
        N Eldredge & SJ Gould [1941 - 2002]: Punctuated Equilibria in fossil record ?
                Process inferrable 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 Molecular Disease (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: 3~5 MYA (!?!) separation,
                                                                    '99%' similar (1975): (!?!)
                    Gene regulation >> change in allelic composition

DNA in ascendancy
        Restriction Fragment Length Polymorphism: RFLPs ("riflips") 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 from RFLP maps of human mtDNA (1987)

        "Sanger" sequencing (1977) method of choice for 40 years (F Sanger: 2nd Nobel Prize 1980)
            Dideoxy DNA sequencing of phage PhiX174 (5,386 bp)
            Human mtDNA "Anderson sequence" (1981); reworked as rCRS (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
            Human Genome Project (1990): implications of Big Machine Biology (GATTACA, 1997)
                Complete E. coil genome sequenced: 4.6 Mbp (1997)

21st Century: Too Much Information
    GenBank (1983 - ): 2,000 sequences => 213.2 Gb (June 2016) [HOMEWORK: How many in Feb 2022?]
            [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.: One Thousand Genomes Project (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