BLAST

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Chapter 2

CHAPTER 2

Biological Sequences

Sequence similarity is a powerful tool for discovering biological function. Just as the

ancient Greeks used comparative anatomy to understand the human body and lin-

guists used the Rosetta stone to decipher Egyptian hieroglyphs, today we can use

comparative sequence analysis to understand genomes, RNAs, and proteins. But why

are biological sequences similar to one another in the first place? The answer to this

question isn’t simple and requires an understanding of molecular and evolutionary

biology.

The Central Dogma of Molecular Biology

Most courses in molecular biology begin with the Central Dogma of Molecular Biol-

ogy, which describes the path by which information contained in DNA is converted

to protein molecules with specific functions. Stated simply, the Central Dogma is:

“from DNA to RNA to protein.” Figure 2-1 shows a more complete diagram of this

process and will be referenced throughout this section.

DNA

The hereditary material that carries the blueprint for an organism from one genera-

tion to the next is called deoxyribonucleic acid. It is much more commonly referred

to by its acronym, DNA. Every time cells divide, the DNA is duplicated in a process

called DNA replication. The entire DNA of an organism is called its genome, and

genomes are sometimes called “the book of life” (especially with respect to the

human genome). Reading and understanding the various books of life is one of the

most important quests of the genomic age. Modern medicine, agriculture, and indus-

try will increasingly depend on an intimate knowledge of genomes to develop indi-

vidualized medicines, select and modify the most desirable traits in plants and

animals, and understand the relationships among species.

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Chapter 2: Biological Sequences

The language of DNA is complicated. Over the last 50 years, scientists have begun to

decipher it, but it is still largely a mystery. Although the language is elusive, the

alphabet is simple, consisting of just four nucleotides: adenine, cytosine, guanine,

and thymine. For simplicity in both speech and on the computer, they are usually

abbreviated as A, C, G, and T. DNA usually exists as a double-stranded molecule,

but we generally talk about just one strand at a time. Here’s an example of a DNA

sequence that is six nucleotides (nt) long:

GAATTC

DNA has polarity, like a battery, but its ends are referred to as 5-prime (5´) and 3-

prime (3´) rather than plus and minus. This nomenclature comes from the chemical

structure of DNA. While it isn’t necessary to understand the chemical structure, the

terminology is important. For example, when people say “the 5´ end of the gene,”

they mean the beginning of the gene. We usually display DNA sequence as we read

text, left to right, and the convention is that the left side is the 5´ end and the right

side is the 3´ end.

Figure 2-1. The Central Dogma of Molecular Biology: DNA to RNA to protein

DNA

Information

Replication

DNA duplicate

Information

Transcription

RNA sythesis

mRNA

Nucleus

Information

Cytoplasm

Nuclear envelope

Translation

Protein sythesis

Protein

RI bosome

Protein

DNA

RNA