Mendel's Century (1900 ~ 2000)
    Classical genetics evolves into molecular genetics           
           
Behavior of crosses versus gene function?
    What is Natural Selection & how does it work?
    How does Natural Selection explain Evolution?


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

1900: Gregor Mendel re-discovered: solves Darwin's biggest worry
          Darwin (1859) relied on “hard genetics": offspring resemble parents
          F Jenkin (1867) shows “blending inheritance” logically incompatible with Selection
              Politically correct “Purple People Eaters
          Mendel
(1867) demonstrated “particulate inheritance

              Purple People Eaters as Green & Yellow Peas
            
        Mendelians versus Biometricians [Pearson versus DeVries]
                Discrete (laboratory) versus Continuous (natural) variation

        GH Hardy (1908) Hardy-Weinberg Theorem sets null hypothesis
        TH Morgan (1910 Genetics of Drosophila
[S&R 1.5] [Nobel Prize, 1936]
        HJ Muller (1926) induced variation by ionizing radiation [Nobel Prize, 1954]
        RA Fisher (1930) Genetical Theory of Natural Selection establishes General Selection Model
                 
Mendelian genetics consistent with incremental Natural Selection
[S&R 1.3]
        S Wright (1931) Evolution in Mendelian Populations
                
Adaptive landscape as metaphor
[S&R 1.4]
                 Random genetic drift important
                 [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 (1937) Genetics and the Origin of Species
                "Evolution is the change in genetic composition of populations"
                Chromosome polymorphism in Drosophila
        E Mayr (1942) Systematics and the Origin of Species
                Allopatric speciation
                Biological Species Concept              
        GG Simpson (1944) Tempo and Mode in Evolution
                Rates & patterns inferred from fossil record
                Evolutionary Species Concept
        GL Stebbins (1950) Variation and Evolution in Plants
                Plant Evolution similar to animal evolution
                Flowering Plants: Evolution Above the Species Level (1974)

        E Mayr (1963) Animal Species & Evolution capstone of Synthesis       
            =>  Natural Selection acting on single genes explains trans-specific evolution
                  Evolution proceeds slowly & gradually
                  Microevolution explains Macroevolution

Challenges to the Synthesis (>1966)
        Molecular Genetics not integrated into Synthesis
        Variation assumed low: Classical versus Balanced schools
                HJ Muller [Morgan School]:          H ~ 0.001
                B Wallace [Dobzhansky School]:  H ~ 1.000
        Punctuated Equilibria in fossil record ?

Molecular Genetics revives Evolution

        DNA structure of gene (1953) (yawn)
        Genetic Code (1965) (Oh?):
DNA > RNA > Protein
        Protein Electrophoresis (1966) in Drosophila, Homo (R Lewontin, F Hubby)
             ***Rapid proliferation of protein variation ("allozyme") studies
                 Lots of variation: is it important ?
                 Neutralist versus Selectionist schools
[S&R 1.9 corrected]
        Molecular Clock
concept from immunogenetic analysis
                Chimp & Human separate 3 ~ 5 MYA
(V Sarich & AC Wilson 1967)
                Chimp & Human 99% similar (MC King & AC Wilson 1975) (!?!)

DNA ascendant
(>1980)
[review S&R 1.6, 1.7, 1.8, Table 1.1]


          Dideoxy sequencing
of phage ØX174 (5,386 bp) (1977)
             
***Sanger” sequencing remains method of choice for 40 years
                     
F Sanger [two Nobel Prizes 1954, 1980]

         RFLP maps of mitochondrial DNA (mtDNA) of natural populations (1979)
             ***
Rapid proliferation of within & among species mtDNA studies
[S&R 1.10]
                    “Out of Africa” hypothesis from RFLP maps of human mtDNA (1987)

        DNA Fingerprinting described; forensic applications (1985)

              ***Rapid proliferation of microsatellite nucDNA population studies

         Polymerase Chain Reaction in vitro amplification of DNA (1983) [S&R 1.11]
                  K Mullis [Nobel Prize 1986]
             
***Rapid proliferation of within & among species DNA studies

         Automated DNA sequencing (1986) uses Sanger method [S&R 1.12]
                   Dideoxy terminators tagged with fluorescent markers: A C G T

              ***Technical developments lead to Next-Gen sequencing
                 
Human mtDNAAnderson” sequence (1981); reworked as rCRS (1999)
                  Human & Great Ape mtDNA genomes compared (1995)

            Complete E. coli genome sequenced: 4.6 Mbp (1997)

           Human Genome Project (1990, completed 2003): Big Science Biology



21st Century: Too Much Information
       GenBank
(1982 - ): 680 Kb => 654 Gb
(August 2020, Release 239) [running count]

       Draft” Human heterochromatic genome 2001, “finished” 2003
            
***Human genome a given:  annotate, interpret, manipulate
                                                            CRISPR-cas technology (2013)

                “Environmental Sequencing” of 1,500 L seawater: 1.2M genes in 1 Gbp (2004)

           One Thousand Genomes Project (1KGP) announced (2008)

            Next-Generation Sequencing  routine from 2012 [S&R 1.13 & 14]

                    Ex. Illumina Sequencing specs:

  Throughput >> 106 nucleotides / second,
              
~ 1 human genome at 1x coverage / hour
               ~ 1 human genome at ~30x coverage / day
           Ex.: NovaSeq 6000s: Complete human genome in 16 hours

*** Waaay too much data: Bioinformatics

   


For further reading:

HF Judson (1996). The Eighth Day of Creation, 2nd ed. Cold Spring Harbor Lab Press.
AH Sturtevant (1965). A History of Genetics [Reprint edition 2001]. Cold Spring Harbor Lab Press.
JD Watson (2012). The Double Helix [Annotated & Illustrated 50th anniversary edition]. Simon & Schuster.


Text material © 2021 by Steven M. Carr