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15

The Molecules of Life

Table 15.5 Some milestones in molecular bioinformatics

Discovery or event

Year

Principal worker(s)

Nuclei contain an acidic substance

1869

Miescher

A tetranucleotide structure elucidated

1919

Levene

DNA identified as genetic material

1944

Avery

First protein (insulin) sequenced

1953

Sanger

DNA double helical structure

1953

Crick, Franklin, Watson

Sequence hypothesis, central dogma

1957

Crick

First protein structure revealed (myoglobin)

1957

Kendrew, Perutz

Semiconservative replication

1958

Meselson and Stahl

DNA polymerase isolated

1959

A. Kornberg

Sequential reading of bases

1961

Crick

First protein sequence data bank

1965

–

Genetic code decrypted

1966

Crick

First protein structure data bank (PDB)

1971

–

First entire genome (H. influenzae) sequenced

1995

–

First multicellular genome

(C. elegans)

1999

–

Human genome project completed

2003

–

High-throughput sequencing

After 2003

–

Online tools

After 2003

Example: UCSC Genome

Browser

Under typical conditions of temperature, acidity, salt concentration, and so on

prevailing in cells, the right-handed (Watson and Crick) double helix is the most

stable structure, but others exist, such as the left-handed helix (Z-DNA), flips to

which may play a rôle in gene activation. Circular DNA can be supercoiled; differing

degrees of supercoiling affect the accessibility of the sequence to RNA polymerase

and is thus a regulatory feature. There are several enzymes (topoisomerases, gyrases,

and helicases) for changing DNA topology.

Double-stranded DNA is a rather rigid polymer, yet, despite its length, if stretched

out in a straight line (about 1.2 mm for the DNA of E. coli), it is nevertheless packed

into a cell only about 1 muµm long. (Human DNA would be about 1 m long.)

A prominent feature of the DNA molecule is its high negative charge density due

to the phosphate groups along the backbone. This gives DNA an ionic strength-

dependent rigidity, which is also a significant factor affecting transcription and

translation.

The rigidity can be quantified by the persistence length German pp, which depends on

Young’s modulus upper EE:

German p equals upper E upper I Subscript s Baseline divided by left parenthesis k Subscript upper B Baseline upper T right parenthesis commap = E Is/(kBT ) ,

(15.2)