Page 54 - Genetics_From_Genes_to_Genomes_6th_FULL_Part3

348 Chapter 10 Genome Annotation

template. This assumption is absolutely incorrect. As pre- genes can be expressed only through the production of
viously shown in Fig. 10.3, neighboring genes can be tran- enormous primary transcripts, their transcription cannot be
scribed either in the same or in opposite directions with completed in rapidly dividing cells. Many big genes are
respect to each other, and either toward the centromere or thus expressed only in neurons, which do not divide. It is
toward the telomere with respect to the chromosome as a possible that scientists have not yet detected some big
whole. Gene maps such as that in Fig. 10.3 typically indi- genes, which might be transcribed into RNA only rarely.
cate the 5′-to-3′ direction of a gene’s transcription (that is, A fundamental unanswered question is whether gene-
the direction that RNA polymerase moves as it copies the rich and/or gene-poor regions have biological meaning. Is
gene into RNA) with an arrow. there a functional explanation for these variations in gene
Because neighboring genes can be transcribed in op- density, or do they instead reflect random fluctuations in
posite directions, RNA polymerase uses the chromosome’s evolutionary events that shape chromosomal architecture?
Watson strand as the template for some genes, while for
other genes, the template is the Crick strand. For most
genes, the direction of transcription appears to be chosen at Genomes Undergo Evolutionary Change
random, or at least no definitive patterns can yet be dis- Genomes continually undergo many different kinds of
cerned. However, in a few exceptional genomic regions, DNA sequence changes that provide the raw material for
such as those containing the hemoglobin genes that will be natural selection. In earlier chapters of this book, you have
described later in this chapter, specific mechanisms of gene encountered some of the events that can alter the nucleo-
regulation require that neighboring genes have the same tide sequence of pre-existing genes: In particular, environ-
transcriptional orientation. mental mutagens and mistakes in DNA replication can

result in nucleotide substitutions. The accumulation of
Variable gene density such point mutations within a gene can certainly change
On average, the density of genes in the human genome is the gene’s function over time. However, as we now de-
slightly less than 1 gene in every 100 kb of DNA (27,000 scribe, analysis of the genomes of humans and other spe-
genes in a 3,000,000 kb genome). However, this rough cies indicates that evolution can also create new genes and
value obscures the fact that the packing of genes can be reorganize genomes by reshuffling blocks of DNA larger
very different in various parts of the genome. Some regions than a single nucleotide. Many kinds of processes promote
on some chromosomes are gene-rich, with little space be- genome plasticity over the evolutionary timeframe.
tween densely packed genes. The most gene-rich region of
the human genome is a 700 kb stretch of chromosome 6
that contains 60 genes encoding histocompatibility pro- Alterations in domain architecture
teins with diverse functions (Fig. 10.7). Genome annotation has revealed that exons often encode
Other regions, called gene deserts, contain few or no discrete protein domains, each of which is a linear se-
genes. The largest known desert in the human genome is quence of amino acids that folds up in three-dimensional
5.1 Mb on chromosome 5 without a single identified gene. space so as to act as a single functional unit. Genes with
Some deserts are gene-poor because they contain so-called multiple exons often encode proteins with multiple domains
big genes whose nuclear transcript spans 500 kb or more of analogous to the cars of a train. Each train is composed of
chromosomal DNA. The largest of the big genes in humans many different cars, and each kind of car (engine, flat car,
is the gene for dystrophin, which spans 2.3 Mb, most of dining car, caboose) has a discrete function. Different trains
which is composed of introns. Interestingly, because big may carry different combinations of cars and thus fulfill

Figure 10.7 Class III region of the human major histocompatibility complex. This densely packed 700 kb–long region
contains 60 genes (colored boxes). Arrows below the genes indicate the direction of each gene’s transcription; just as in Fig. 10.3, some
genes are transcribed in one direction and others in the opposite direction.
CYP C4B CYP C4A B144
21B 21Ps G11 G5b CKII 1C7 LTB NB6
G16 YB ZB YA ZA G11a Hsp70 BAT5 G3a TNF lkBL
RAGE XA RD G10 HOM G7c G7d G5 K18L LTA
PBX2 G15 TN-X 21 G4
G18 G14 XB-S B1 G9 G7b G6 G3 G1 BAT1
NOTCH4 G13 C2 G9a G8 G7a G7 G6a G2

1200 1300 1400 1500 1600 1700 1800 1900
class II Major histocompatibility complex class III class I