BIOL 213- lecture 10: DNA and chromosomes

Genome evolution

The gradual change in the DNA sequence and structure of genomes over generations.

Source of differences between individuals

Small differences in DNA sequence account for differences in appearance between individuals of the same species.

Mutation within a gene

A change in a gene's DNA sequence that can alter the protein it encodes.

Mutation in regulatory DNA

A change in a regulatory sequence that alters when or how much a gene is expressed (e.g., less mRNA is made).

Gene duplication and divergence

A gene is duplicated, then each copy accumulates different mutations over time.

Exon shuffling

Exons from one gene are moved into another gene, creating hybrid proteins with new combinations of domains.

Mobile genetic element (transposition)

A DNA sequence that moves to a new location in the genome, e.g., into the regulatory region of a gene.

Horizontal gene transfer

Transfer of genes from one organism to another (not from parent to offspring).

Germ-line cells

Cells (gametes, i.e., eggs and sperm, and the cells that produce them) that pass genetic information to the next generation. Gametes have half the number of chromosomes of other body cells.

Somatic cells

All body cells other than germ-line cells. They form the body but do not pass their DNA to the next generation.

Zygote

The fertilized egg, with a full chromosome set. It gives rise to both germ-line cells and somatic cells.

Fertilization

Fusion of two gametes to form a zygote.

Germ-line mutation

A mutation in a germ-line cell. It can be inherited by offspring (present in every cell of the offspring), so it can become part of evolution.

Somatic mutation

A mutation in a somatic cell. It affects only that cell's descendants within the individual and is not passed to offspring.

Somatic mutations and disease

Somatic mutations are responsible for most human cancers.

Lactose tolerance (lactase persistence)

The ability of adults to digest lactose (milk sugar) because the lactase gene stays expressed after childhood.

Why lactase persistence spread

About 10,000 years ago humans in northern Europe and central Africa began raising cattle. Adults able to digest milk had a selective advantage, especially during starvation.

Lactase persistence mutations

Two independent point mutations in regulatory DNA near the lactase gene (G to C in northern Europe, C to T in central Africa) allow lactase expression in adults and spread through those populations.

Geographic pattern of lactose tolerance

High in northern Europe and some African populations; low in eastern Asia.

Short repetitive DNA sequences (in gene duplication)

Repeated sequences on either side of a gene that can pair incorrectly between homologous chromosomes.

Misalignment

Homologous chromosomes pair out of register using different repeats.

Unequal crossing-over

Crossing-over between misaligned repeats. It gives one longer chromosome with a duplicated gene and one shorter chromosome that lacks the gene.

Single-chain globin

The ancestral globin protein; binds one O2 molecule using a heme group.

Hemoglobin

A four-chain protein (two alpha and two beta chains) that binds four O2 molecules cooperatively. It evolved by gene duplication followed by mutation.

Cooperative binding

Binding of oxygen to one hemoglobin chain makes binding to the other chains easier.

Globin gene family

On human chromosome 11: epsilon, gamma-G, gamma-A, delta and beta genes. The alpha-globin genes are elsewhere.

Fetal vs. adult globin

Different duplicated globin copies are expressed at different developmental stages (gamma in the fetus, beta in the adult), giving specialized oxygen-binding properties.

Time scale of globin evolution

Globin duplications and divergence spanned roughly 500+ million years.

Polyploidy

Having more than two complete sets of chromosomes (N = ploidy).

Ploidy of crop plants

Apple and potato: 4N (tetraploid). Wheat and kiwi: 6N (hexaploid). Sugarcane and strawberry: 8N (octoploid).

Why whole-genome duplication persists in crops

Plant breeders select it because it can make plants easier to cultivate or give larger, more flavorful or seedless fruit.

Potato karyotype

A tetraploid potato cell has four copies of each of 12 different chromosomes.

Protein domain

A part of a protein with a distinct structure and function, often encoded by one or a few exons.

Result of exon shuffling

New combinations of domains (e.g., EGF-like and protease domains) produce proteins such as urokinase, Factor IX and plasminogen, which share domains with chymotrypsin and EGF.

Effect of a transposable element on body plan

Movement of a transposable element into a regulatory sequence can dramatically alter development.

Drosophila legs-for-antennae mutant

A fly with legs in place of antennae, caused by a regulatory mutation that activates leg-forming genes where antennae should form.

Teosinte

The wild ancestor of corn; many branches with many small, hard-seeded ears.

Modern corn

Fewer, larger cobs with many plump kernels.

Role of a mobile element in corn evolution

Insertion of a mobile genetic element near a gene involved in seed development helped drive the change from teosinte to corn.

Conjugation

Bacterial cells exchange DNA through direct contact; a form of horizontal gene transfer.

Sex pilus

A fine appendage by which a donor bacterial cell captures a recipient cell; DNA moves from donor to recipient through it.

Phylogenetic tree

A diagram of evolutionary relationships among species, based on how recently they shared a common ancestor.

Sequence divergence and time

Genome sequences of two species differ in proportion to the time since they diverged.

Great ape branching order

Human and chimpanzee share the most recent common ancestor (about 6 million years ago), then gorilla, then orangutan.

Axes of the primate tree figure

Percent difference in nucleotide sequence (left) and estimated millions of years since divergence (right).

Ancestral sequence reconstruction

Comparing closely related species (e.g., human, chimp, gorilla) lets us infer the sequence the common ancestor had, e.g., the base shared by most species.

Mobile elements in the human beta-globin cluster

L1 (red) and Alu (green) elements.

Mobile elements in the mouse beta-globin cluster

B1 (blue) and L1 (brown) elements.

Why mobile element positions differ between human and mouse

The long evolutionary time separating the species; insertions continued independently after they diverged.

Purifying selection

Natural selection that removes harmful mutations, so functionally important sequences stay conserved.

Sequence conservation in close species (e.g., human vs. chimp): noncoding exons

Conserved, but with some base additions or losses.

Sequence conservation in close species: coding sequences

Conserved with few DNA changes and few or no protein changes. Insertions or deletions occur in runs of three (preserving the reading frame).

Sequence conservation in close species: introns

Change more rapidly; conserved near splice junctions and diverge in the middle.

Sequence conservation in more diverged species (e.g., human vs. mouse): noncoding exons

Conserved, with more differences than in close species.

Sequence conservation in more diverged species: coding sequences

Conserved; third-position (silent) changes are common and there are few amino acid changes.

Sequence conservation in more diverged species: introns

Change rapidly; conserved only near splice junctions.

Mammalian conserved intron sequences

Short intron regions that are highly conserved across mammals, likely regulatory.

Fugu rubripes

The puffer fish, which has a remarkably compact genome.

Fugu gene structure

Fugu genes have the same exons as human genes but far shorter introns and less intergenic DNA, so the gene is much shorter. This makes Fugu useful for finding conserved gene elements.

Ancient conservation of rRNA

The gene for the small ribosomal subunit rRNA is conserved among human (eukaryote), Methanococcus (archaeon) and E. coli (bacterium). It shows some genetic information has been conserved since the beginnings of life.

Red dot in the rRNA alignment

A site where a nucleotide was deleted in one lineage or inserted in the others.

Small-subunit rRNA as a molecular ruler

The more similar the rRNA sequences of two species, the more recently they diverged from a common ancestor.

Three domains of life

Bacteria, Archaea and Eukaryotes.

Visible organisms and life's diversity

Animals, plants and some fungi are only a small part of life's diversity as measured by DNA sequence.

Transposon (transposable element)

A mobile genetic element that moves within or between genomes.

Cut-and-paste transposition

The element is excised from the donor DNA and inserted into a target site, leaving a broken donor DNA that is repaired.

Replicative transposition

The element is copied by DNA replication; the donor remains unchanged and the target receives a copy.

Transposase

The enzyme encoded by a transposon that catalyzes its movement.

Transposon recognition sequences

DNA sequences at the ends of the transposon that are recognized by its transposase.

Bacterial transposon examples

IS3 and Tn3.

Antibiotic resistance gene in transposons (AmpR)

Some transposons carry genes that inactivate antibiotics such as ampicillin, helping resistance spread among pathogens.

How transposons move exons between genes

If two similar transposable elements insert near each other, the transposase may recognize ends of two different elements and move the DNA between them, so an exon from gene A can be inserted into gene B, creating a novel gene or altering regulation.

Retrotransposon

A mobile element that moves via an RNA intermediate: DNA to RNA (transcription), RNA to DNA copy (reverse transcription), then insertion into a new site.

Reverse transcriptase

Enzyme that makes a DNA copy from an RNA template.

Retrotransposon copy-and-paste

The original stays in place, so each transposition duplicates the element.

Backward flow of information

The RNA-to-DNA step in retrotransposition.

DNA viruses that cause human disease

Herpes simplex (cold sores), Epstein-Barr (mononucleosis), varicella-zoster (chicken pox and shingles), smallpox, hepatitis B (partly single-, partly double-stranded DNA; serum hepatitis).

Single-stranded RNA viruses that cause human disease

HIV (AIDS), influenza A (flu), polio, rhinovirus (common cold), hepatitis A and C, yellow fever, rabies, mumps, measles.

Virus

A genome (DNA or RNA) in a protein coat (capsid), sometimes inside a lipid envelope; it can only reproduce inside a host cell.

Viral envelope

A lipid bilayer with viral proteins around some viruses (e.g., poxvirus, HIV). Others (papilloma, polio) have only a protein coat.

Virus size range

From about 50 nm (polio) to about 800 nm (Ebola, thread-like).

Steps of viral replication

Entry; genome replication using host machinery; transcription and translation of coat protein; assembly of new particles; exit (often by lysing the cell).

SARS-CoV-2 genome

Single-stranded RNA of about 30,000 nucleotides, packaged with an RNA-binding protein and enclosed in a lipid envelope with spike proteins.

Spike protein

Viral surface protein used to attach to and enter host cells.

SARS-CoV-2 replication cycle

Entry and loss of envelope; host ribosomes translate the genome; RNA-dependent RNA polymerase (replicase) is made; replicase makes complementary RNA; that RNA is the template for new genomes and mRNAs; viral proteins are translated; particles assemble.

RNA-dependent RNA polymerase

Coronavirus-specific enzyme that copies RNA from an RNA template.

Retrovirus (e.g., HIV)

An RNA virus that copies its genome into DNA and integrates it into host DNA.

Reverse transcriptase in retroviruses

Packaged with the viral RNA; makes an RNA-DNA hybrid and then double-stranded DNA.

Retroviral integration

The DNA copy is inserted into a host chromosome, which is required for host RNA polymerase to make new viral RNA.

Retrovirus genome size

Typically 7,000 to 12,000 nucleotides of RNA.

Human chromosome 22

Example chromosome with two DNA molecules of 48 x 10^6 nucleotide pairs each; zooming in shows few genes, lots of noncoding DNA, and genes split into exons and introns.

Human genome total length

About 3.1 x 10^9 nucleotide pairs (2.85 billion known precisely).

Number of human protein-coding genes

Approximately 20,000.

Number of human non-protein-coding genes

Approximately 5,000 (structural, catalytic and regulatory RNAs).

Largest human protein-coding gene; median gene size

Largest: 2.5 x 10^6 nucleotide pairs. Median: 26,000 nucleotide pairs.

Exons per human gene

Smallest 1, largest 363, median 9.

Human exon size

Largest 17,106 nucleotide pairs; median 131 nucleotide pairs.

Number of human pseudogenes

More than 20,000.

Pseudogene

A sequence resembling a functional gene but with mutations that prevent expression. Often arises from duplication followed by damaging mutations in one copy.

Percent of human DNA that encodes protein (exons)

0.8%.