Nucléotidos y ácidos nucleicos

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“Discovering the DNA”
• Johannes Friedrich Miescher (13 August 1844, Basel - 26 August 1895, Davos)
was a Swiss physician and biologist. He isolated various phosphate-rich chemicals,
which he called nuclein (now nucleic acids), from the nuclei of white blood cells in 1869 at
Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany, paving the way
for the identification of DNA as the carrier of inheritance (published in 1871).

• Gregor Mendel discovered the laws or rules of heredity in 1866.

• Walter Sutton (1877-1916) and Theodor Boveri (1862-1915) independently proposed

that the hereditary information is carried in the chromosomes (1902). The made the
connection between genetics and cell biology (and molecular biology).

• Frederick Griffith bacterial transformation in 1928

Griffith's experiments proving that a nonvirulent form of bacteria (the R form) can
be converted to a virulent form (the S form) by a transforming agent. That agent was
later identified as DNA, the genetic material.
 “Discovering the DNA”
• Johannes Friedrich Miescher (13 August 1844, Basel - 26 August 1895, Davos) was a Swiss physician and
biologist. He isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of
white blood cells in 1869 at Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany, paving the way for
the identification of DNA as the carrier of inheritance (published in 1871).

• Gregor Mendel discovered the laws or rules of heredity in 1866.

• Walter Sutton (1877-1916) and Theodor Boveri (1862-1915) independently proposed that the hereditary
information is carried in the chromosomes (1902). The made the connection between genetics and cell biology (and
molecular biology).

• Frederick Griffith bacterial transformation in 1928

• Oswald Avery (1877-1955), Colin MacLeod (1909-1972) and Maclyn McCarty (1911-
2005) published the first experiment to demonstrate that DNA was the genetic material, in
1944 .
 Avery, McLeod and McCarthy’s experiment demostrated that DNA was the
genetic material responsible for Griffith’s results (not RNA).

Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
 “Discovering the DNA”
• Johannes Friedrich Miescher (13 August 1844, Basel - 26 August 1895, Davos) was a Swiss physician and
biologist. He isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of
white blood cells in 1869 at Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany, paving the way
for the identification of DNA as the carrier of inheritance (published in 1871).

• Gregor Mendel discovered the laws or rules of heredity in 1866.

• Walter Sutton (1877-1916) and Theodor Boveri (1862-1915) independently proposed that the hereditary
information is carried in the chromosomes (1902). The made the connection between genetics and cell biology (and
molecular biology).

• Frederick Griffith bacterial transformation in 1928

• Oswald Avery (1877-1955), Colin MacLeod (1909-1972) and Maclyn McCarty (1911-2005) published the first
experiment to demonstrate that DNA was the genetic material, in 1944.

• 1950, HACIA LA ESTRUCTURA DEL DNA ...

• Erwin Chargaff (1905-2002) discovered that the amounts of adenine and thymine in
DNA were roughly the same, as were the amounts of cytosine and guanine. This later
became known as the third of Chargaff's rules (1950).
 Base composition studies of Erwin Chargaff

• indicated double-stranded DNA consists of ~50% purines (A,G)

and ~50% pyrimidines (T, C)

• amount of A = amount of T and amount of G = amount of C

(Chargraff’s rules)

• %GC content varies from organism to organism

Examples: %A %T %G %C %GC

Homo sapiens 31.0 31.5 19.1 18.4 37.5

Zea mays 25.6 25.3 24.5 24.6 49.1
Drosophila 27.3 27.6 22.5 22.5 45.0
Aythya americana 25.8 25.8 24.2 24.2 48.4

• the base composition in a given species does not changes with an

organism’s age, nutritional state, or changing environment
 “Discovering the DNA”
• Johannes Friedrich Miescher (13 August 1844, Basel - 26 August 1895, Davos) was a Swiss physician and
biologist. He isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of
white blood cells in 1869 at Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany, paving the way
for the identification of DNA as the carrier of inheritance (published in 1871).

• Gregor Mendel discovered the laws or rules of heredity in 1866.

• Walter Sutton (1877-1916) and Theodor Boveri (1862-1915) independently proposed that the hereditary
information is carried in the chromosomes (1902). The made the connection between genetics and cell biology (and
molecular biology).

• Frederick Griffith bacterial transformation in 1928

• Oswald Avery (1877-1955), Colin MacLeod (1909-1972) and Maclyn McCarty (1911-2005) published the first
experiment to demonstrate that DNA was the genetic material, in 1944.

• 1950, HACIA LA ESTRUCTURA DEL DNA ...

• Erwin Chargaff (1905-2002) discovered that the amounts of adenine and thymine in DNA were roughly the same, as
were the amounts of cytosine and guanine. This later became known as the third of Chargaff's rules (1950).

• Maurice Wilkins (1916-2004) and Rosalind Franklin (1920-1958) They have

discovered that DNA produces a characteristic X-ray diffraction pattern, helical, with two
periodicities along their long axis.
R. Franklin DNA fiber X-ray diffraction data
• This picture actually shows all the
important information about the double
helix.

• X-shaped Pattern is created when X-Ray

move through helical shape (helical angle
diameter of 20 Å

• Diffraction takes place at angles

perpendicular to the helix

• Four white diamond shapes indicate

repeating pattern above and below the
central 'X’

• Density measurements suggest 2 or 3-

stranded helix
From this image one can calculate the most important
dimensions of DNA

3.4 Å

10 Å

34 Å
 “Discovering the DNA”
• Johannes Friedrich Miescher (13 August 1844, Basel - 26 August 1895, Davos) was a Swiss physician and
biologist. He isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of
white blood cells in 1869 at Felix Hoppe-Seyler's laboratory at the University of Tübingen, Germany, paving the way
for the identification of DNA as the carrier of inheritance (published in 1871).

• Gregor Mendel discovered the laws or rules of heredity in 1866.

• Walter Sutton (1877-1916) and Theodor Boveri (1862-1915) independently proposed that the hereditary
information is carried in the chromosomes (1902). The made the connection between genetics and cell biology (and
molecular biology).

• Frederick Griffith bacterial transformation in 1928

• Oswald Avery (1877-1955), Colin MacLeod (1909-1972) and Maclyn McCarty (1911-2005) published the first
experiment to demonstrate that DNA was the genetic material, in 1944.

• 1950, HACIA LA ESTRUCTURA DEL DNA ...

• Erwin Chargaff (1905-2002) discovered that the amounts of adenine and thymine in DNA were roughly the same, as
were the amounts of cytosine and guanine. This later became known as the third of Chargaff's rules (1950).

• Maurice Wilkins (1916-2004) and Rosalind Franklin (1920-1958) They have discovered that DNA produces a
characteristic X-ray diffraction pattern, helical, with two periodicities along their long axis.

• James D. Watson (1928- )and Francis H. Crick (1916-2004) proposed

the Double Helix Model in 1953
Modelo 3D de estructura del ADN: doble
hélice

1.- En base a:

- Las reglas de Chargaff

- Estudios de difracción de rayos X (Rosalind Franklin &

Maurice Wilkins)

2.- Características:

- dos cadenas helicoidales de ADN que giran sobre el mismo

eje para formar una doble hélice con “torsión diestra” (right-
handed dobule helix), giro de 36 grados/base, 10.5 bases por
vuelta de hélice (34 Å), diámetro de 20 Å. El giro de las hélices
puede formar surcos pequeños (minor) y surcos grandes
(mayor)

- cada hélice es un polímero de nucleótidos en el que el

esqueleto hidrófilico de los azúcares y fosfatos está hacia el
exterior de la hélice; mientras que las bases nitrogenadas,
hidrofóbicas, con estructura casi planar, perpendicular al eje
longitudinal, se orientan hacia el interior de la hélice con una
separación entre bases de 3.4 Å.
-
2.- Características...

- las hebras o cadenas de nucleótidos son anti-paralelas, es

decir, tienen direccionalidad opuesta (respecto a los enlaces
5’-3’ fosfodiester)

- los pares de bases entre hélices (cadenas o hebras) están

unidos por puentes de hidrógeno

- en las hebras, las bases nitrogenadas tienen interacción no

específica tipo “apilamiento” (stacking), y contribuye a la
estabilidad de la doble hélice

- los pares de bases entre hélices son complementarios (purina-

pirimidina)

(A-T y G-C)
Composición de la cadena o hebra de ácido nucleico (ADN y ARN)
- formada por residuos o nucleótidos cuya estructura general está
formada por una base nitrogenada (purina o pirimidina), un azucar
(deoxirribosa en ADN o ribosa en ARN) y un grupo fosfato
Pentosa

El anillo de pentosa no es plano y presenta una

variedad de conformaciones (“puckered” o arrugadas)

C-3’ exo

C-2’ endo
Base Base

C-3’ exo

C-2’ exo
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 Enlace glucosídico: pentosa-base nitrogenada

(N-ß-glycosyl bond
formed by removal of
water elements
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Base
 (purine or pyrimidine)

(N-ß-glycosyl bond
formed by removal of
water elements
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Enlace 3’-5’
fosfodiester
Puentes de
hidrógeno
ADN cadena doble

Purine + Purine = Too

wide

Pyrimidine + Pyrimidine
= Too Narrow

Purine + Pyrimidine = Perfect

Fit from X-ray data
 Estructuras de ADN alternativas
ADN-A ADN-B ADN-Z

los surcos
son más
parecidos
en anchura:

Más surco Más

mayor
corta estrecho y larga
profundo
el surco mayor
no existe, es muy
surco poco profundo
menor
19º ancho y
superficial
bases algo surco menor,
inclinadas: profundo y
9º estrecho

dextrógira levógira