Essential Cell Biology 5th edition

Examining the Human Genome
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The task was not simple. An international consortium of investigators
labored tirelessly for the better part of a decade—and spent nearly
$3 billion—to give us our first glimpse of this genetic blueprint. But the
effort turned out to be well worth the cost, as the data continue to shape
our thinking about how our genome functions and how it has evolved.
The first human genome sequence was just the beginning. The spectacular
improvements in sequencing technologies (which we discuss
in Chapter 10), coupled with powerful new tools for handling massive
amounts of data, are taking genomics to a whole new level. The cost
of DNA sequencing has dropped enormously since the Human Genome
Project was launched in 1990, such that a whole human genome can now
be sequenced in a few days for about $1000. Investigators around the
world are collaborating to collect and compare the nucleotide sequences
of thousands of human genomes. This resulting deluge of data offers tantalizing
clues as to what makes us human, and what makes each of us
unique.
Although it will take many years to analyze the rapidly accumulating
genome data, the recent findings have already influenced the content of
every chapter in this book. In this section, we describe some of the most
striking features of the human genome—many of which were entirely
unexpected. We review what genome comparisons can tell us about how
we evolved, and we discuss some of the mysteries that still remain.
The Nucleotide Sequences of Human Genomes Show
How Our Genes Are Arranged
When the DNA sequence of human Chromosome 22, one of the smallest
human chromosomes, was completed in 1999, it became possible for
the first time to see exactly how genes are arranged along an entire vertebrate
chromosome (Figure 9−32). The subsequent publication of the
QUESTION 9–6
Mobile genetic elements, such as
the Alu sequences, are found in
many copies in human DNA. In what
ways could the presence of an Alu
sequence affect a nearby gene?
(A)
Human Chromosome 22 in its mitotic conformation,
composed of two double-stranded DNA molecules, each 48 × 10 6 nucleotide pairs long
heterochromatin
×10
(B)
10% of the long chromosome arm (~40 genes)
×10
(C)
1% of the whole chromosome (containing 4 genes)
×10
(D)
exon
single gene of 3.4 × 10 4 nucleotide pairs
intron
Figure 9−32 The sequence of Chromosome 22 shows how human chromosomes are organized. (A) Chromosome 22, one of the
smallest human chromosomes, contains 48 × 10 6 nucleotide pairs and makes up approximately 1.5% of the human genome. Most of
the short arm of Chromosome 22 consists of short repeated sequences of DNA that are packaged in a particularly compact form of
chromatin (heterochromatin), as discussed in Chapter 5. (B) A tenfold expansion of a portion of Chromosome 22 shows about 40 genes.
Those in dark brown are known genes, and those in red are predicted genes. (C) An expanded portion of (B) shows the entire length
of several genes. (D) The intron–exon arrangement of a typical gene is shown after a further tenfold expansion. Each exon (red) codes
for a portion of the protein, while the DNA sequence of the introns (yellow) is relatively unimportant. (Adapted from The International
Human Genome Sequencing Consortium, Nature 409:860–921, 2001.)
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