Mendel's Century

Mendel's Century (1900 ~ 2000)
    Classical genetics evolves into molecular genetics
            Analysis of crosses versus gene function
            Genetic data directly available from Protein & DNA sequences

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) showed “blending inheritance” logically incompatible with Selection
              Politically correct “Purple People Eaters”
          Mendel (1867) demonstrated “particulate inheritance”
              Purple People Eaters as Green & Yellow Peas

        GH Hardy (1908) Hardy-Weinberg Theorem sets null hypothesis
        RA Fisher (1930) Genetical Theory of Natural Selection establishes General Selection Model
                Mendelian genetics consistent with incremental Natural Selection
    S Wright (1931) Evolution in Mendelian Populations
                 Adaptive landscape as metaphor
                 Random genetic drift important

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 adaptive
        E Mayr (1942) Biological species concept; Allopatric speciation
        GG Simpson (1944) Rates & patterns in fossil record; Evolutionary species concept
        GL Stebbins (1950) Plant evolution similar to animal evolution
        E Mayr (1963) Animal Species & Evolution capstone of Synthesis
=> Natural Selection acting on single genes explains trans-specific evolution
                  Evolution proceeds slowly & gradually
                    Variation measured as Heterozygosity (H):
        H low: Classical vs Balanced schools differ on how low
                  Microevolution explains Macroevolution
                        Species differences

Genus differences

etc by accumulated change
        Stumbling block: inter-species genetic differences not measurable

Molecular Genetics (slowly) revives Evolution
        DNA structure of gene (1953) (yawn)
        Genetic Code (1965): DNA > RNA > Protein
        Protein Electrophoresis (1966) in Drosophila, Homo
           ***Rapid proliferation of protein variation studies: allozymes
               Lots of variation: is it important ?
                 Neutralist versus Selectionist school succeeds Classical / Balanced argument
        Molecular Clock concept from immuno-genetic analysis (1967)
                Ex.: Chimp & Human separate 3 ~ 5 MYA (!?!)
                        98.6% = "99%" similar (!!??!!) (King & Wilson, 1975)

DNA data ascendant (>1980)

       RFLP maps of mitochondrial DNA (mtDNA) (1979)
             ***Rapid proliferation of within & among species mtDNA studies
          Ex.: “Out of Africa” hypothesis from RFLP maps of human mtDNA (1987)

         Dideoxy DNA sequencing (1977, routine from 1990)

*** "Sanger” sequencing remained method of choice for 40 years

DNA Fingerprinting described; forensic applications (1985)

*** Rapid proliferation of microsatellite nucDNA population studies

Polymerase Chain Reaction in vitro amplification of DNA (1983)

*** Rapid proliferation of within & among species DNA studies

         Automated DNA sequencing (1986) uses Sanger method

                   Dideoxy terminators tagged with fluorescent markers: A C G T
                   E. coli genome sequenced: 4.6 Mbp (1997)
                   Human Genome Project: 3,200 Mbp (2003): "Big Science" comes to Biology
    ***Technical developments lead to Next-Gen sequencing

21st Century: Too Much Information (?)
GenBank: >1 Terabases (December 2023, Release 239)
[running count: (October 2024: 4,250,942,573,681]

Data base for identification, retrieval, annotation, interpretation, manipulation, etc
CRISPR-cas technology (2013)

Ex.: “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

             Ex. Illumina Sequencing specs:
Throughput >> 10⁶nucleotides / second,
                      ~ 1 human genome at 1x coverage / hour
      ~ 1 human genome at ~30x coverage / day

Complete human genome in 16 hour

*** "Here it comes: assimilate it."
Waaay too much data: Bioinformatics