william bateson - department of molecular & cell...

11
MCB140 01-29-07 1 Genetics – the narrative so far 1. Mendel (1853-66): 1. Heredity operates via particles of information (=genes). 2. For any trait, two particles (=alleles of a gene) come together in an organism, but then separate into gametes, one per gamete. 3. This process occurs independently for particles (genes) for different traits. 2. Häckel, Weissmann, Flemming, Boveri (1850-1900): 1. The nucleus of the cell is the organelle that is reponsible for heredity (Hääckel, Boveri), and specific kinds of cells (the gametes) that are separate and distinct from the rest of the body, are responsible for generating progeny (Weissman). 2. Inside the cell, lie the chromosomes (Flemming) that separate into daughter cells via mitosis. 3. Proper development of an organism requires a specific set of a particular kind of chromosome (Boveri). 3. Sutton (and Cannon) – 1902. 1. There is a striking concordance between the behavior of Mendel’s particles and chromosomes during meiosis. MCB140 01-29-07 2 Genetics – the narrative to come 1. Morgan and Bridges – genes lie on chromosomes (1910-1915). 2. Bateson and Sturtevant (1906-15) – some genes appear to be physically linked; the nature of this linkage is the following: genes are arranged on a chromosome in a linear order, at particular distances from each other. 3. McClintock and Stern (1930) – genetic recombination occurs when homologous chromosomes can exchange parts. 4. Beadle and Tatum (1946) – some genes affect the development of traits by encoding biochemical functions (“one gene = one enzyme”). 5. Muller (1927) – the gene can be purposefully mutated. 6. Benzer – the gene itself can be split into smaller units. 7. Studying the molecular makeup of life via: 1. The genetic screen – use of purposeful mutagenesis to identify genes required for the development of various traits. 2. Mapping by linkage and association mapping – the study of “simple” and “complex” traits by analysis of pedigrees and populations. MCB140 01-29-07 3 What is being omitted for lack of time 1. The rediscovery of Mendel’s laws by Correns, Tschermak, and de Vries. 2. The finding – by Cuenot and by Castle – that Mendel’s laws also apply to mammals, such as mice and guinea pigs. MCB140 01-29-07 4 William Bateson “… he privately subsidized his small book, Mendel’s Principles of Heredity: A Defence and he sent copies to all of the leading students of heredity to make sure that Mendel would not suffer another 35 years of neglect.” Carlson Mendel’s Legacy

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  • 1

    MC

    B14

    0 01

    -29-

    07 1

    Gen

    etic

    s –

    the

    narr

    ativ

    e so

    far

    1.M

    ende

    l (18

    53-6

    6):

    1.H

    ered

    ity o

    pera

    tes

    via

    parti

    cles

    of i

    nfor

    mat

    ion

    (=ge

    nes)

    .2.

    For a

    ny tr

    ait,

    two

    parti

    cles

    (=al

    lele

    s of

    a g

    ene)

    com

    e to

    geth

    er in

    an

    orga

    nism

    , but

    then

    sep

    arat

    e in

    to g

    amet

    es, o

    ne p

    er g

    amet

    e.3.

    This

    pro

    cess

    occ

    urs

    inde

    pend

    ently

    for p

    artic

    les

    (gen

    es) f

    or d

    iffer

    ent

    traits

    .2.

    Häc

    kel,

    Wei

    ssm

    ann,

    Fle

    mm

    ing,

    Bov

    eri (

    1850

    -190

    0):

    1.Th

    e nu

    cleu

    s of

    the

    cell

    is th

    e or

    gane

    lle th

    at is

    repo

    nsib

    le fo

    r her

    edity

    (H

    ääck

    el, B

    over

    i), a

    nd s

    peci

    fic k

    inds

    of c

    ells

    (the

    gam

    etes

    ) tha

    t are

    se

    para

    te a

    nd d

    istin

    ct fr

    om th

    e re

    st o

    f the

    bod

    y, a

    re re

    spon

    sibl

    efo

    r ge

    nera

    ting

    prog

    eny

    (Wei

    ssm

    an).

    2.In

    side

    the

    cell,

    lie

    the

    chro

    mos

    omes

    (Fle

    mm

    ing)

    that

    sep

    arat

    e in

    to

    daug

    hter

    cel

    ls v

    ia m

    itosi

    s.3.

    Pro

    per d

    evel

    opm

    ent o

    f an

    orga

    nism

    requ

    ires

    a sp

    ecifi

    c se

    t of a

    pa

    rticu

    lar k

    ind

    of c

    hrom

    osom

    e (B

    over

    i).3.

    Sutto

    n (a

    nd C

    anno

    n) –

    1902

    .1.

    Ther

    e is

    a s

    triki

    ng c

    onco

    rdan

    ce b

    etw

    een

    the

    beha

    vior

    of M

    ende

    l’spa

    rticl

    es a

    nd c

    hrom

    osom

    es d

    urin

    g m

    eios

    is.

    MC

    B14

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    07 2

    Gen

    etic

    s –

    the

    narr

    ativ

    e to

    com

    e1.

    Mor

    gan

    and

    Brid

    ges

    –ge

    nes

    lie o

    n ch

    rom

    osom

    es (1

    910-

    1915

    ).2.

    Bat

    eson

    and

    Stu

    rteva

    nt (1

    906-

    15) –

    som

    e ge

    nes

    appe

    ar to

    be

    phys

    ical

    ly

    linke

    d; th

    e na

    ture

    of t

    his

    linka

    ge is

    the

    follo

    win

    g: g

    enes

    are

    arr

    ange

    d on

    a

    chro

    mos

    ome

    in a

    line

    ar o

    rder

    , at p

    artic

    ular

    dis

    tanc

    es fr

    om e

    ach

    othe

    r.3.

    McC

    linto

    ck a

    nd S

    tern

    (193

    0) –

    gene

    tic re

    com

    bina

    tion

    occu

    rs w

    hen

    hom

    olog

    ous

    chro

    mos

    omes

    can

    exc

    hang

    e pa

    rts.

    4.B

    eadl

    e an

    d Ta

    tum

    (194

    6) –

    som

    e ge

    nes

    affe

    ct th

    e de

    velo

    pmen

    t of t

    raits

    by

    enc

    odin

    g bi

    oche

    mic

    al fu

    nctio

    ns (“

    one

    gene

    = o

    ne e

    nzym

    e”).

    5.M

    ulle

    r (19

    27) –

    the

    gene

    can

    be

    purp

    osef

    ully

    mut

    ated

    .6.

    Ben

    zer –

    the

    gene

    itse

    lf ca

    n be

    spl

    it in

    to s

    mal

    ler u

    nits

    .7.

    Stu

    dyin

    g th

    e m

    olec

    ular

    mak

    eup

    of li

    fe v

    ia:

    1.Th

    e ge

    netic

    scr

    een

    –us

    e of

    pur

    pose

    ful m

    utag

    enes

    is to

    iden

    tify

    gene

    s re

    quire

    d fo

    r the

    dev

    elop

    men

    t of v

    ario

    us tr

    aits

    .2.

    Map

    ping

    by

    linka

    ge a

    nd a

    ssoc

    iatio

    n m

    appi

    ng –

    the

    stud

    y of

    “sim

    ple”

    and

    “c

    ompl

    ex” t

    raits

    by

    anal

    ysis

    of p

    edig

    rees

    and

    pop

    ulat

    ions

    .

    MC

    B14

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    -29-

    07 3

    Wha

    t is

    bein

    g om

    itted

    fo

    r lac

    k of

    tim

    e1.

    The

    redi

    scov

    ery

    of M

    ende

    l’s la

    ws

    by

    Cor

    rens

    , Tsc

    herm

    ak, a

    nd d

    e V

    ries.

    2.Th

    e fin

    ding

    –by

    Cue

    not a

    nd b

    y C

    astle

    –th

    at M

    ende

    l’s la

    ws

    also

    app

    ly to

    m

    amm

    als,

    suc

    h as

    mic

    e an

    d gu

    inea

    pi

    gs.

    MC

    B14

    0 01

    -29-

    07 4

    Willi

    am B

    ates

    on

    “…he

    priv

    atel

    y su

    bsid

    ized

    his

    sm

    all b

    ook,

    Men

    del’s

    Prin

    cipl

    es

    of H

    ered

    ity: A

    Def

    ence

    and

    he

    sent

    cop

    ies

    to a

    ll of

    the

    lead

    ing

    stud

    ents

    of h

    ered

    ity to

    mak

    e su

    re

    that

    Men

    del w

    ould

    not

    suf

    fer

    anot

    her 3

    5 ye

    ars

    of n

    egle

    ct.”

    Car

    lson

    Men

    del’s

    Leg

    acy

  • 2

    MC

    B14

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    07 5

    Mod

    ified

    Men

    delia

    n ra

    tios

    epis

    tasi

    s

    MC

    B14

    0 01

    -29-

    07 6

    “Rep

    ulsi

    on a

    nd c

    oupl

    ing”

    linka

    ge

    MC

    B14

    0 01

    -29-

    07 7

    Bat

    eson

    190

    2M

    CB

    140

    01-2

    9-07

    8B

    ates

    on 1

    902

    αλληλος

    = "e

    ach

    othe

    r"

  • 3

    MC

    B14

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    07 9

    Fig.

    3.7

    MC

    B14

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    -29-

    07 1

    0

    Thom

    as H

    unt M

    orga

    n, th

    e fir

    st n

    ativ

    e-bo

    rn A

    mer

    ican

    to w

    in th

    e N

    obel

    Priz

    e,

    foun

    der o

    f mod

    ern

    gene

    tics

    Brid

    ges

    Mul

    ler

    Mor

    gan

    Stu

    rteva

    nt

    MC

    B14

    0 01

    -29-

    07 1

    2

    Mor

    gan

    et a

    l. 19

    15

    “As

    will

    be s

    how

    n no

    w, c

    erta

    in fa

    ctor

    s fo

    llow

    th

    e di

    strib

    utio

    n of

    the

    X c

    hrom

    osom

    e an

    d ar

    e th

    eref

    ore

    supp

    osed

    to b

    e co

    ntai

    ned

    in th

    em.”

    Em

    phas

    is m

    ine

    –fd

    u.

    ↓G

    enes

    lie

    on c

    hrom

    osom

    es

  • 4

    MC

    B14

    0 01

    -29-

    07 1

    3

    “The

    sup

    posi

    tion

    that

    par

    ticle

    s of

    ch

    rom

    atin

    , ind

    istin

    guis

    habl

    e fro

    m

    each

    oth

    er a

    nd in

    deed

    alm

    ost

    hom

    ogen

    eous

    und

    er a

    ny

    know

    n te

    st, c

    an b

    y th

    eir m

    ater

    ial

    natu

    re c

    onfe

    r all

    the

    prop

    ertie

    s of

    lif

    e su

    rpas

    ses

    the

    rang

    e of

    eve

    n th

    e m

    ost c

    onvi

    nced

    mat

    eria

    lism

    .”

    Bat

    eson

    , W. (

    1916

    ) The

    m

    echa

    nism

    of M

    ende

    lian

    here

    dity

    (a

    revi

    ew).

    Sci

    ence

    , 44,

    536

    -543

    .

    MC

    B14

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    -29-

    07 1

    4

    MC

    B14

    0 01

    -29-

    07 1

    5

    A p

    robl

    em a

    nd a

    sol

    utio

    n“T

    he v

    alue

    and

    util

    ity o

    f any

    exp

    erim

    ent…

    ” (M

    ende

    l)“W

    hat w

    as n

    eede

    d to

    ope

    n up

    gen

    etic

    s to

    new

    ph

    enom

    ena

    was

    an

    orga

    nism

    that

    bre

    d ra

    pidl

    y,

    prod

    uced

    lots

    of p

    roge

    ny, a

    nd w

    as in

    expe

    nsiv

    e to

    mai

    ntai

    n” (C

    arls

    on)

    “Fru

    it fli

    es c

    an b

    e ra

    ised

    on

    a m

    ixtu

    re o

    f cor

    n m

    eal,

    yeas

    t, su

    gar,

    and

    agar

    . Flie

    s co

    mpl

    ete

    thei

    r life

    cy

    cle

    from

    ferti

    lizat

    ion

    to e

    mer

    genc

    e of

    the

    adul

    t fly

    in 1

    0 da

    ys. A

    fem

    ale

    can

    prod

    uce

    3,00

    0 pr

    ogen

    y in

    her

    life

    time.

    A s

    ingl

    e m

    ale

    can

    sire

    w

    ell o

    ver 1

    0,00

    0 of

    fspr

    ing.

    ” (H

    artw

    ell)

    MC

    B14

    0 01

    -29-

    07 1

    6

    (aka

    chr

    . 1)

    Not

    e: n

    o cr

    ossi

    ng o

    ver i

    n m

    ale

    mei

    osis

    !

  • 5

    MC

    B14

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    07 1

    8

    Mor

    gan

    and

    Dro

    soph

    ila(g

    o B

    ears

    )M

    orga

    n w

    as n

    ota

    gene

    ticis

    t by

    train

    ing

    (he

    was

    an

    embr

    yolo

    gist

    ), an

    d he

    w

    as n

    otth

    e fir

    st o

    ne to

    use

    Dro

    soph

    ila fo

    r pur

    pose

    s of

    gen

    etic

    rese

    arch

    (C

    astle

    was

    ).“O

    ne o

    f the

    baf

    fling

    pro

    blem

    s of

    bre

    eder

    s in

    pre

    -Men

    delia

    n da

    ys h

    ad

    been

    the

    effe

    cts

    of in

    bree

    ding

    and

    cro

    ssbr

    eedi

    ng. W

    hat t

    hese

    wer

    e w

    as

    a m

    uch-

    deba

    ted

    ques

    tion.

    We

    set o

    ut to

    giv

    e it

    an e

    xper

    imen

    tal t

    est a

    ndfo

    und

    read

    y to

    han

    d a

    rapi

    dly

    bree

    ding

    littl

    e fly

    , Dro

    soph

    ila, b

    eing

    cu

    lture

    d in

    the

    labo

    rato

    ry b

    y a

    grad

    uate

    stu

    dent

    as

    embr

    yolo

    gica

    l m

    ater

    ial.

    This

    , he

    told

    us,

    wou

    ld c

    ompl

    ete

    a ge

    nera

    tion

    with

    in a

    fortn

    ight

    . (C

    harle

    s W

    oodw

    orth

    , pro

    f ent

    omol

    ogy

    at U

    C B

    erke

    ley)

    . … W

    e b

    egan

    cultu

    ring

    the

    fly o

    n pu

    lped

    Con

    cord

    gra

    pes,

    but

    this

    gav

    e us

    poo

    r res

    ults

    as

    man

    y of

    the

    larv

    ae w

    ould

    get

    dro

    wne

    d an

    d th

    en o

    ur p

    opul

    atio

    n st

    atis

    tics

    wer

    e no

    goo

    d. A

    s gr

    apes

    bec

    ame

    out o

    f sea

    son,

    we

    tried

    oth

    er

    fruits

    , and

    fina

    lly h

    it th

    e ja

    ckpo

    t in

    bana

    nas.

    …Th

    e co

    nclu

    sion

    dra

    wn

    [from

    our

    stu

    dies

    ] was

    that

    inbr

    eedi

    ng re

    duce

    s ve

    ry s

    light

    ly th

    epr

    oduc

    tiven

    ess

    of D

    roso

    phila

    . … T

    his

    was

    not

    a c

    oncl

    usio

    n of

    wor

    ld-

    shak

    ing

    impo

    rtanc

    e. T

    he im

    porta

    nt o

    utco

    me

    of th

    is in

    vest

    igat

    ion

    was

    that

    it

    calle

    d to

    Mor

    gan’

    s at

    tent

    ion

    a ne

    w s

    ourc

    e of

    mat

    eria

    l for

    exp

    erim

    enta

    l st

    udy

    not s

    ubje

    ct to

    the

    limita

    tions

    of s

    low

    -bre

    edin

    g la

    bora

    tory

    mam

    mal

    s.”

    WE

    Cas

    tle (p

    rof g

    enet

    ics

    UC

    Ber

    kele

    y) T

    he B

    egin

    ning

    s of

    Men

    delis

    m in

    A

    mer

    ica

    –in

    Gen

    etic

    s in

    the

    20th

    Cen

    tury

    , p. 7

    3.

    MC

    B14

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    07 1

    9

    Toug

    h ea

    rly g

    oing

    “…M

    orga

    n ha

    d be

    en w

    orki

    ng

    on fr

    uit f

    lies

    for a

    t lea

    st tw

    o ye

    ars

    befo

    re h

    e fo

    und

    his

    mos

    t sig

    nific

    ant m

    utat

    ion,

    a

    whi

    te-e

    yed

    fly. F

    or th

    is n

    ew

    appr

    oach

    , Mor

    gan

    was

    his

    ow

    n fir

    st s

    tude

    nt. H

    e br

    ed

    the

    flile

    s fo

    r tw

    o ye

    ars

    with

    out a

    ssis

    tanc

    e. …

    He

    poin

    ted

    to th

    e sh

    elve

    s w

    ith

    flies

    and

    [sai

    d] th

    at h

    e ha

    d w

    aste

    d tw

    o ye

    ars

    and

    had

    gotte

    n no

    thin

    g fo

    r his

    wor

    k.”

    MC

    B14

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    07 2

    0

    “May

    191

    0 w

    as w

    hen

    the

    revo

    lutio

    n be

    gan.

    Mor

    gan

    foun

    d a

    whi

    te-e

    yed

    mal

    e ru

    nnin

    g ar

    ound

    in o

    ne b

    ottle

    .”

  • 6

    MC

    B14

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    1

    Gre

    at o

    peni

    ng p

    assa

    ges

    in th

    e hi

    stor

    y of

    the

    Eng

    lish

    lang

    uage

    “It is

    a tr

    uth

    univ

    ersa

    lly a

    ckno

    wle

    dged

    that

    a

    sing

    le m

    an in

    pos

    sess

    ion

    of a

    goo

    d fo

    rtune

    m

    ust b

    e in

    wan

    t of a

    wife

    .”

    “Whe

    n C

    arol

    ine

    Mee

    ber b

    oard

    ed th

    e af

    tern

    oon

    train

    for C

    hica

    go, h

    er to

    tal o

    utfit

    co

    nsis

    ted

    of a

    sm

    all t

    runk

    , a c

    heap

    imita

    tion

    allig

    ator

    -ski

    n sa

    tche

    l, a

    smal

    l lun

    ch in

    a

    pape

    r box

    , and

    a y

    ello

    w le

    athe

    r-sn

    ap p

    urse

    , co

    ntai

    ning

    her

    tick

    et, a

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  • 8

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  • 9

    MC

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  • 11

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    -29-

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