GENES AND CHROMOSOMES

Genes Code for Proteins

One gene: One enzime

One gene : One polypeptide

or RNA

Dominance is explained by the properties of mutant proteins

Mutations in the same gene cannot complement

Mutations: Loos of function or gain of

function

Recombination ocurrs by physical exchange of DNA

The code genetic is triplet Every sequence hasthree possible reading

frames

Several processes are required to express the protein product of a gene

Proteins are trans acting Sites on DNA are cis acting

THE INTERRUPTED GENE

Some genes possess only one o few introns

Some DNA sequences code for more than one polypeptide

Some exons can be equated with protein functional domains

The Content of the Genome:

The genome

The transcriptome

The proteome

The interactome

Figure 05.01: A point mutation that affects a restriction site is detected by a difference in restriction fragment lengths.

Individual Genomes Show Extensive Variation

Figure 05.03: A restriction polymorphism can be used as a genetic marker to measure

recombination distance from a phenotypic marker.

Figure 05.04: If a restriction marker is associated with a phenotypic characteristic, the restriction site must be located near the gene for the phenotype.

Eukaryotic Genomes Contain Both Nonrepetitive and Repetitive DNA Sequences

A large part of moderately repetitive DNA may be made up of transposons. Figure 05.05: The proportions of different sequence

components vary in eukaryotic genomes.

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.

Figure 05.10: DNA from the sperm enters the oocyte to form the male pronucleus in the egg, but all the

mitochondria are provided by the oocyte.

Organelle Genomes Are Circular DNAs That Encode Organelle Proteins

Organelle genomes are usually (but not always) circular molecules of DNA.Mitochondrial DNA (mtDNA)Chloroplast DNA (cpDNA or ctDNA)

Organelle genomes encode some, but not all, of the proteins used in the organelle.

Figure 05.11: Mitochondrial genomes have genes encoding (mostly complex I–IV) proteins,

rRNAs, and tRNAs.

Organelle Genomes Are Circular DNAs That Encode Organelle Proteins

Figure 05.12: Human mitochondrial DNA has 22 tRNA genes, two rRNA genes, and 13

protein-coding regions.

The Chloroplast Genome Encodes Many Proteins and RNAs Chloroplast genomes vary in size, but are large enough

to encode 50 to 100 proteins as well as rRNAs and tRNAs.

Figure 05.14: The chloroplast genome in land plants encodes 4

rRNAs, 30 tRNAs, and ~60 proteins.

Genome sequences and gene numbers

Figure 06.01: The minimum gene number required for any type of organism increases with its complexity.

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Prokaryotic Gene Numbers Range Over an Order of Magnitude

The minimum number of genes for a parasitic prokaryote is about 500; for a free-living nonparasitic prokaryote it is about 1500.

Figure 06.02: Genome sizes and gene numbers are known from complete sequences for

several organisms.

Figure 06.03: The number of genes in bacterial and archaeal genomes is proportional to genome size.

Total Gene Number Is Known for Several Eukaryotes

There are 6000 genes in yeast; 21,700 in a nematode worm; 17,000 in a fly; 25,000 in the small plant Arabidopsis; and probably 20,000 to 25,000 in mice and humans.

Figure 06.04: The number of genes in a eukaryote varies from 6000-

40,000 but does not correlate with genome size or the organism

complexity.

Figure 06.05: The S. cerevisiae genome of 13.5 Mb has 6000 genes, almost all uninterrupted.

Total Gene Number Is Known for Several Eukaryotes

Figure 06.06: Functions of Drosophila genes based on comparative genomics of twelve species.

Adapted from Drosophila 12 Genomes Consortium, “Evolution of genes and genomes on the Drosophila phylogeny,” Nature 450 (2007): 203–218.

How Many Different Types of Genes Are There?

The sum of the number of unique genes and the number of gene families is an estimate of the number of types of genes.

Figure 06.07: Many genes are duplicated,

and as a result the number of different

gene families is much less than the total number of genes.

How Many Different Types of Genes Are There?

orthologous genes (orthologs) – Related genes in different species.

The minimum size of the proteome can be estimated from the number of types of genes.

Figure 06.09: Fruit fly genome can be divided into genes present in all eukaryotes, genes present in all multicell eukaryotes, genes specific to flies.

The Human Genome Has Fewer Genes Than Originally Expected Only 1% of the human genome consists of exons. The exons comprise ~5% of each gene, so genes

(exons plus introns) comprise ~25% of the genome.

The human genome has 20,000 to 25,000 genes.

Figure 06.11: Genes occupy 25% of the human genome, but protein-coding sequences are only a

small part of this fraction.

The Human Genome Has Fewer Genes Than Originally Expected

Figure 06.12: The average human gene is 27 kb long and has nine exons, usually comprising two longer exons at each end and seven internal exons.

The Human Genome Has Fewer Genes Than Originally Expected ~60% of human genes are alternatively spliced.

Up to 80% of the alternative splices change protein sequence, so the proteome has ~50,000 to 60,000 members.

How Are Genes and Other Sequences Distributed in the Genome?

Repeated sequences (present in more than one copy) account for >50% of the human genome.

The great bulk of repeated sequences consists of copies of nonfunctional transposons.

There are many duplications

of large chromosome regions.

Figure 06.14: The largest component of the human genome consists of transposons.

The Y Chromosome Has Several Male-Specific Genes

The Y chromosome has ~60 genes that are expressed specifically in the testis.

The male-specific genes are present in multiple copies in repeated chromosomal segments.

Gene conversion between multiple copies allows the active genes to be maintained during evolution.

Figure 06.15: The Y chromosome consists of X-transposed regions,

X-degenerate regions, and amplicons.

How Many Genes Are Essential?

Not all genes are essential. In yeast and flies, deletions of <50% of the genes have detectable effects.

When two or more genes are redundant, a mutation in any one of them may not have detectable effects.

Figure 06.16: Essential yeast genes are found in all classes.

How Many Genes Are Essential?

We do not fully understand the persistence of genes that are apparently dispensable in the genome.

Figure 06.17: A systematic analysis of loss of function

for 86% of worm genes shows that only 10% have detectable effects on the

phenotype.

About 10,000 Genes Are Expressed at Widely Differing Levels in a Eukaryotic Cell mRNAs expressed at low levels overlap

extensively when different cell types are compared.housekeeping gene – A gene that is (theoretically)

expressed in all cells because it provides basic functions needed for sustenance of all cell types.

The abundantly expressed mRNAs are usually specific for the cell type.luxury gene – A gene encoding a specialized function,

(usually) synthesized in large amounts in particular cell types.

~10,000 expressed genes may be common to most cell types of a multicellular eukaryote.

6.10 Expressed Gene Number Can Be Measured En Masse

DNA microarray technology allows detailed comparisons of related animal cells to determine (for example) the differences in expression between a normal cell and a cancer cell.

Figure 06.22: Heat map of 59 invasive breast tumors from women who breastfed ≥6 months (red lines) or who never breastfed (blue lines).

Image courtesy of Rachel E. Ellsworth, Clinical Breast Care Project, Windber Research Institute.

Clusters and Repeats gene family pseudogenes gene cluster

7.1 Introduction

satellite DNA – DNA that consists of many tandem repeats (identical or related) of a short basic repeating unit.

minisatellite – DNAs consisting of tandemly repeated copies of a short repeating sequence, with more repeat copies than a microsatellite but fewer than a satellite.The length of the repeating unit is measured in tens

of base pairs.The number of repeats varies between individual

genomes.

Unequal Crossing Over Rearranges Gene Clusters

When a genome contains a cluster of genes with related sequences, mispairing between nonallelic loci can cause unequal crossing over.This produces a deletion in one recombinant

chromosome and a corresponding duplication in the other.

Unequal Crossing Over Rearranges Gene Clusters

Figure 07.04: Gene number can be changed by unequal crossing over.

Unequal Crossing Over Rearranges Gene Clusters

Different thalassemias are caused by various deletions that eliminate α- or β-globin genes.The severity of the disease

depends on the individual deletion.

Figure 07.05: α-thalassemias result from various deletions in the α-

globin gene cluster.

Mammalian Satellites Consist of Hierarchical Repeats

Figure 07.17: The alignment of eighth-repeats shows that each quarter-repeat consists of an α and a β half.

Minisatellites Are Useful for Genetic Mapping

The variation between microsatellites or minisatellites in individual genomes can be used to identify heredity unequivocally by showing that 50% of the bands in an individual are inherited from a particular parent.

variable number tandem repeat (VNTR) – Very short repeated sequences, including microsatellites and minisatellites.

Minisatellites Are Useful for Genetic Mapping

Figure 07.20: Alleles may differ by number of repeats at a minisatellite

locus, so digestion generates restriction fragments that differ in length.

Chromosomes

Centromere

Telomeres

Nucleosome

Tetramero H3-H4 Dimero H2A-H2B

Dos copias