Transcript Chapter 4

Chapter 4
The Content of the Genome
4.1
Introduction
 The transcriptome and proteome of a cell are
generally smaller than its genome
 The transcriptome and proteome of the whole
organism are generally larger than its genome.
4.2
Genomes Can Be Mapped at Several
Levels of Resolution
• Linkage maps are based on the frequency of
recombination between genetic markers.
– Restriction maps are based on the physical distances
between markers.
• Molecular characterization of mutations can be
used to reconcile linkage maps with physical
maps.
4.2
Genomes Can Be Mapped at Several
Levels of Resolution
Figure 4.01: Some point mutations change the restriction map.
4.3
Individual Genomes Show Extensive
Variation
• Polymorphism may be detected:
– at the phenotypic level when a sequence affects gene
function
– at the restriction fragment level when it affects a
restriction enzyme target site
– at the sequence level by direct analysis of DNA
• The alleles of a gene show extensive
polymorphism at the sequence level, but many
sequence changes do not affect function.
4.3
Individual Genomes Show Extensive
Variation
Figure 4.02: Restriction sites show Mendelian inheritance.
Photo courtesy of Ray White, Ernest Gallo Clinic and Research Center,
University of California, San Francisco
4.4
RFLPs and SNPs Can Be Used for
Genetic Mapping
• RFLPs and SNPs can be the basis for linkage
maps.
• They are useful for establishing parent–offspring
relationships.
Figure 4.03: RFLPs are genetic markers.
4.4
RFLPs and SNPs Can Be Used for
Genetic Mapping
Figure 4.04: RFLPs can be associated with disease genes.
4.5
Why Are Some Genomes So Large?
• There is no clear correlation between genome
size and genetic complexity.
Figure 4.05: Is DNA content related to
morphological complexity?
4.5
Why Are Some Genomes So Large?
• There is an increase in the minimum genome
size required to make organisms of increasing
complexity.
• There are wide variations in the genome sizes of
organisms within many taxa.
4.5
Why Are Some Genomes So Large?
Figure 4.06: Minimum genome size increases with the taxon.
Figure 4.07: Comparison of genome sizes.
4.6 Eukaryotic Genomes Contain Both
Nonrepetitive and Repetitive DNA Sequences
• The kinetics of DNA reassociation after a genome has
been denatured distinguish sequences by their
frequency of repetition in the genome.
• Polypeptides are generally coded by sequences in
nonrepetitive DNA.
• Larger genomes within a taxon do not contain more
genes, but have large amounts of repetitive DNA.
• A large part of moderately repetitive DNA may be made
up of transposons.
Figure 4.08: Nonrepetitive DNA is only part of the genome.
4.7
Eukaryotic Protein-Coding Genes Can Be
Identified by the Conservation of Exons
• Conservation of exons can be used as the basis
for identifying coding regions by identifying
fragments whose sequences are present in
multiple organisms.
• Human disease genes are identified by mapping
and sequencing DNA of patients to find
differences from normal DNA that are genetically
linked to the disease.
4.7 Eukaryotic Protein-Coding
Genes Can Be Identified by the
Conservation of Exons
Figure 4.09: Genes can be identified by deletions.
Figure 4.10: The DMD gene codes for a muscle protein.
Figure 4.11: A special vector is used for exton trapping.
4.8 The Conservation of Genome
Organization Helps to Identify Genes
• Methods for identifying active genes are not
perfect and many corrections must be made to
preliminary estimates.
• Pseudogenes must be distinguished from active
genes.
• There are extensive syntenic relationships
between the mouse and human genomes, and
most active genes are in a syntenic region.
Figure 4.12: Exons are identified by flanking sequences and ORFs.
Figure 4.13: Syntenic blocks vary in length.
4.9
Some Organelles Have DNA
• Mitochondria and chloroplasts have genomes
that show non-Mendelian inheritance.
– Typically they are maternally inherited.
• Organelle genomes may undergo somatic
segregation in plants.
• Comparisons of mitochondrial DNA suggest that
it is descended from a single population that
lived 200,000 years ago in Africa.
4.9
Some Organelles Have DNA
Figure 4.14: Uneven segregation causes somatic variation.
Figure 4.15: Animal mtDNA is inherited from the mother.
4.10 Organelle Genomes Are Circular DNAs
That Code for Organelle Proteins
• Organelle genomes are usually (but not always)
circular molecules of DNA.
• Organelle genomes code for some, but not all, of
the proteins found in the organelle.
4.10 Organelle Genomes Are Circular DNAs
That Code for Organelle Proteins
• Animal cell mitochondrial DNA is extremely
compact and typically codes for 13 proteins, 2
rRNAs, and 22 tRNAs.
• Yeast mitochondrial DNA is 5× longer than
animal cell mtDNA because of the presence of
long introns.
4.10 Organelle Genomes Are Circular DNAs
That Code for Organelle Proteins
Figure 4.16: Mitochondria code for RNAs
and proteins.
Figure 4.17: Most human mtDNA
is expressed.
Figure 4.17: Most human mtDNA is expressed.
4.11 The Chloroplast Genome Codes for Many
Proteins and RNAs
• Chloroplast genomes vary in size, but are large
enough to code for 50 to 100 proteins as well as
the rRNAs and tRNAs.
Figure 4.19: Chloroplasts have >100 genes.
4.12 Mitochondria and Chloroplasts Evolved by
Endosymbiosis
• Both mitochondria and chloroplasts are
descended from bacterial ancestors.
• Most of the genes of the mitochondrial and
chloroplast genomes have been transferred to
the nucleus during the organelle’s evolution.
4.12 Mitochondria and
Chloroplasts Evolved by
Endosymbiosis
Figure 4.20: Endosymbiosis results from cell
capture.