Introduction to Biology

Molecules and Cells

Chapter 7 - DNA, Genetics, and Reproduction 

DNA in Cells

A cell stores the basic information it needs to do everything it can do in DNA codes - genes - that can be used to make all of its proteins, including enzymes used to make almost everything else.  But it doesn't carry a bunch of separate pieces of DNA - the genes are stuck together on chromosomes.

When the cell makes offspring cells, all of the genes need to be copied, and a copy of each needs to get into each new cell.  The fewer pieces that must be copied and distributed, the better the chance that it will be done properly.  This is why genes are linked together on chromosomes.  Chromosomes also carry other important pieces - stretches that control how genes are read and spliced, stretches that allow interactions when other genes are activated, stretches that code for many different types of functional RNA.  There is also a lot of DNA in a chromosome whose function, if it exists, is unknown - those are often used for genetic comparisons, since mutations in a non-functional part of a chromosome should be passed along to offspring with no selection acting on them.

Species have their own characteristic chromosome number.  For prokaryotes, it's typically one;  for eukaryotes, it's usually an even number, since they carry matched pairs of homologous chromosomes.  Low chromosome numbers are better for cell division:  fewer pieces, fewer mistakes.  High chromosome numbers tend toward more mistakes, but can be sorted out in many more combinations.  This produces higher variation in offspring, very important in evolution.

More on the relationship of genes to chromosomes, specifically in humans.

Linkage of some disease-related alleles on human chromosomes.

Some different species' chromosome numbers.

Image of human chromosomes (colors added), showing 22 types in homologous pairs plus the sex chromosomes.

Chromosomes are not just DNA, but a complex of DNA and special packaging proteins called histones that allow a long strand of DNA to be spooled and coiled into a small place.  These proteins produce chromosomes with thick or thin spots, or even with light and dark stripes. Chromosomes also have special structures, centromeres, that hold copies together and are used to move them around during cell division.  Each species has a particular karyotype - an analysis of their chromosomes by total number, then by the shape of each one.

Since the packaging varies along the chromosomes, some genes can be easier or more difficult to access when the protein is produced.  Changes in the packaging patterns can happen, change how the gene is expressed, and affect features without an actual change of the gene sequence.

Eukaryote chromosomes are two-ended, and the ends have a special "cap" called a telomere.  Because of the way DNA gets copied, the very end would be uneven if a special enzyme called telomerase didn't fix it.  In many species, including us, telomerase stops being produced in many cells as we age, and our chromosomes "fray at the ends," until the cells won't make new copies and so can't make cells to replace damaged ones;  this is one of the causes of aging.

Levels of chromosome structure.

More on structure.

Karyotype - actual spread and assembly of types.

Telomeres, aging, and cancer.

Telomerase used to extend mousey lifespans.

Telomeres and telomerase.

Homologous chromosomes are sorted into single sets for sexual reproduction for a special type of cell division called meiosis, whose steps will be covered later in this chapter.  One set will be mixed with another single set, producing two sets in a new combination.  Even in organisms that sexually reproduce with themselves, offspring will get new combinations of chromosomes.

Gender is a common factor in sexual reproduction (not always - many fungi reproduce with no gender roles at all, and some use way more than two), and usually there is a male role and a female role.  How can you tell which from which?  It's not what you're thinking (could you apply that to a tree?) - what determines those genders is only what sort of gametes (sex cells) they produce.  Males produce sperm, females produce egg cells, also called ova.  There are very particular features for each:

When two genders are not enough.

Sperm production.

Egg cell production.

In many species with gender, what makes an individual male or female involves interaction with its environment while it's developing.  In other species, sex chromosomes determine gender.  This may involve an unmatched pair, where one gender has a matched pair and the other has a   unmatched set (such as in mammals, where males have the unmatched pair, or birds, where females have it).  In some species, one gender gets a singlet, only one sex chromosome, and the other gender gets a doublet, a matched pair.  Genes carried on sex chromosomes are said to be sex-linked, and in show different genetic patterns than genes on the other chromosomes (the other chromosomes are called autosomes;  humans have sex-linked disorders and autosomal chromosome disorders that indicate where the genes are).

In the unmatched-pair form of gender expression, the gender with two matched chromosomes may deactivate one of them, so both genders only use one.  In humans, the deactivated chromosome can be stained, showing a Barr body that only genetic females should have.

Human sex chromosomes.
 

Evolution of 3 different unmatched pairs.
 

Sex linkage for human Y chromosome (not seriously).
 

Some sex-linked disorders of humans.
 

More on the Barr Body.

DNA in Action

DNA molecules are two strands of nitrogenous bases cross-connected, set up like a twisted ladder or helix  (DNA is famously known as a double helix molecule).  In DNA there are four nitrogenous bases, and they pair up in a set way:  Adenine cross-connects to thymine (A-T), and cytosine cross-connects to guanine.  This makes the molecules easy to copy reliably:  during replication, the strands are separated and new strands are built across from the originals:  wherever an A was across from a T, only an A should fit there when the new strand is being constructed.  That means that every "copy" made is half new and half old.  Since this molecule contains almost every bit of information needed for a new cell to be functional, it is critical to make good copies of each chromosome for the new cells.

Eukaryote cells have an array of proteins that work to make new DNA copies in preparation for making new cells.  There are the enzymes that do the actual work, as well as a number of proofreading proteins that check that the copying goes correctly.  Even so, mistakes get made that are passed along to the new cells:  this is one type of mutation.  Viruses use the cell's copying enzymes to make DNA for new viruses, but they often don't use the proofreaders.  This is both good and bad for the viruses, as a lot of mistakes will produce many poorly-functioning offspring, but the rare improvement.  What often causes an HIV infection to progress to HIV-AIDS is the production of what's called an escape mutant:  a virus that the body's defenses or treatments can't hold in check.

Lots on DNA structure.

Video showing DNA replication.

HIV escape mutants.

When a cell needs to make a particular protein, a chemical message travels to the nucleus, and bits of a chromosome near the gene for that protein activate.  That part of the DNA molecule separates, and on one side, a molecule of messenger RNA (mRNA) is made from the gene sequence in a process called transcription.  Where there is a cytosine, there will be a guanine on the mRNA, and vice versa;  a thymine on the DNA will have an adenine connected there;  an adenine on the DNA will not have a thymine across from it, but a similar base called uracil.  Every three bases on the mRNA are a codon.  Most codons code for particular amino acids in the final protein, but the first and last codon have other functions.  The first one in the sequence is a start codon and marks where the mRNA will be built (that codon inside the sequence, codes for the amino acid methionine), and the last codon is a stop codon, which causes transcription to stop.

The mRNA may get manipulated before it leaves the nucleus.  It isn't unusual for some pieces to be clipped out and not used, and some to be spliced together in a new sequence different from the original.

Transcription video.

Animation.

The mRNA (actually, there should be at least two of them, from the codes on homologous chromosomes) travel from the nucleus to the ribosomes, where translation happens.  The mRNA fits into a furrow on the ribosome and crawls along and out;  as it is on the ribosome, molecules of transfer RNA (tRNA) attach to it briefly with a 3-base sequence called an anticodon (again, the bases pair up in a set way, and there are as many tRNAs as there are codon sequences).  Also attached to the tRNA is an amino acid;  as the tRNAs bind, one after the other, to the mRNA, they bring in and leave a sequence of amino acids, building a protein.

As the end of the mRNA feeds through the ribosome, the protein sequence emerges with it.  It turns out that some amino acid sequences can, if just left alone, curl up into many different shapes, only one of which is the one the cell needs.  There are special proteins called chaperonins that make certain that the protein takes the proper functional shape.

Prions are a type of infective protein that apparently get into cells and change the shape of a functional into a prion - you lose the protein function, and it can now do the same thing to more proteins.  Mad cow disease is thought to be a prion disease.

Translation.

 

mRNA codon-to-amino-acid table.

 

Another animation.

 

Test your understanding.

 

Possible prion diseases.

Mutations are a change in DNA - anything from a single change in a single base on the sequence (a point mutation) up to entire extra sets of chromosomes (which are associated with new species in plants, but usually fatal to animals).

Point mutations may involve the wrong base getting into a sequence, a substitution mutation.  Most point mutations happen in the non-coding parts of the DNA (since there's more of it than the coding parts) and have little effect.  If a substitution changes the codon in a gene, the code has some redundancy:  often a changed codon codes for the same amino acid, or a very similar one.  This is probably how most new alleles arise.  When a substitution really changes one amino acid into another, it still may not alter the function of the final protein;  human, cow, and pig insulin differ in some amino acids, but have the same functionality.  But changes can really alter the effects of a protein.  Recessive alleles often produce non-functioning proteins;  dominant alleles produce proteins with comparatively powerful effects, strong enough to cover the effects of a recessive.  When alleles produce proteins with different effects usually there's more of a combination effect:  these can be called blended, intermediate, or codominant allele effects.  One particularly dangerous mutation changes a regular codon into a stop codon, stopping the transcription at that point.

If a base is mistakenly cut out of a sequence (a deletion) or a base is squeezed between two where it shouldn't be (an addition), a frame shift occurs:  every codon "downstream" from the mutation is shifted over a spot.  This should produce a very different, probably non-functional protein, although it might rarely produce a protein with a brand-new yet useful function.

Types of mutations.

Animation of mutation effect.

Recessive & dominant inheritance.

Frameshift effect.

Larger-scale mutations happen as well.  DNA molecules often break and need to be stuck back together with DNA repair proteins.  There is a limit to what the repair mechanism can handle:  multiple simultaneous breaks may result in pieces being put back in the wrong place, being put in backwards, or a piece being lost from its original chromosome.  Some chemicals or radiation types can cause many DNA breaks, with such mutations.  Since most DNA is non-coding and in any given cell, only some codes get used, these mutation often show effects only in cells that divide.  During division, loose pieces get copied but not properly distributed, and new cells that have too many or too few copies of genes they need can make the wrong amounts of proteins, hurting the cells.  This can cause cells to become cancerous, but it is also used to try to kill cancers.

Translocations happen when a piece of a chromosome is moved to another place, usually on another chromosome.  These may produce position effects by putting the piece in a place that is easier or harder to get to for processing, increasing or decreasing its expression rate.  It may add genetic information as well, if an offspring gets an "enhanced" chromosome from one homologous set but the unaffected member of the pair the piece came from.

More on DNA repair.

Repair enzymes go where they are needed.

More on translocations.

Mutations on a whole-chromosome level happen fairly often:  a cell divides, but a chromosome copy goes the wrong way, giving one cell extra genes and one cell fewer.  In an early stage of development, those genes are likely to be used and the individual is likely to be damaged:  in humans, for instance, when an egg cell or sperm sends on an extra or missing chromosome to offspring, those offspring often die early.  Of the 24 types of human chromosomes, we can usually only survive an extra Number 21 (which even though small, still causes Down Syndrome), an extra X (any more than one gets converted into a non-functional Barr Body), and an extra Y (which only carries male-related genes).  Later in development, if cell division mistakes send on extra or missing chromosomes, effects depend on whether those chromosomes hold critical genes for that cell type.  One type of mosaicism, where an individual has patches of genetically-different cells, is caused this way.

Karyotype of Down Syndrome.

Cells Making Cells

Depending upon the type of reproduction involved, there are two types of cell reproduction:  mitosis produces cells that are genetically identical to the original, the definition of asexual reproduction;  when sexual reproduction produces a mixture of genes, meiosis makes cells with just one set of chromosomes, to be recombined with another set and get a new mix.  Technically, both are actually terms applied to making new nuclei:  mitosis produces two diploid (2X, two sets of chromosomes) nuclei, and meiosis produces four haploid (1X, one set of chromosomes) nuclei.  However, it's common to use the terms to describe cell divisions.

Cells that are going to make more cells go through something called a cell cycle.  The cycle is divided into phases.

Interphase is the stage that most cells are in most of the time, because it is the between-divisions stage during which a cell does its job.  A cell that is not going to divide just does its job in interphase until it dies (many human cell types do this).  If the cell is going to divide, it chemically prepares during interphase, building up the components it will need to make the structures active during a division, including copies of its chromosomes.

Cell cycle.

Animation.

Prophase is the first active stage of a division.  The copied chromosomes get gathered into extremely condensed forms, so they can be easily moved around without tangling.  Chromosomes aren't visible under a light microscope during interphase, but they become visible during prophase, first as strands of chromatin, then as double-stranded chromosomes.  Each strand is called a chromatid.

Outside the nucleus, at opposite ends of the cell (called the poles), centrioles begin to build microtubules, which radiate out in all directions.  These are called spindle fibers or just spindle.  Some of them attach to the membrane and hold the centrioles in place;  others move across the cell and will connect to the centromeres that hold the two strands of the double-stranded chromosomes together.  However, the chromosomes are in the nucleus and the spindles are outside;  the nuclear envelope must get out of the way for them to get together.  The nucleus and nucleoli disassemble and disappear from view.

Spindles from both poles grab chromosomes by the centromeres and pull on them, with longer spindles pulling harder.  Eventually the chromosomes stall in the middle zone (the equator) of the cell, with equal-length spindles on  each side.  Prophase is to set up this condition:  put the copies where they can be reliably separated and pulled apart.

Prophase.

Spindle chromosome connection.

Not a lot happens during metaphase, and you might think it should go by very quickly, but a cell might stall here for a while.  The length of time for each phase can vary greatly from cell to cell.  The cell is in metaphase from the time that most of the chromosomes settle into the equator to the time that a chemical release causes the centromeres to break apart, separating the strands.  Each copy is attached to an opposing spindle, and they get pulled away from each other.

Metaphase.

In anaphase, the now single-stranded chromosomes are moved well away from each other.  Once they are far enough apart, a cell could begin cytokinesis, the actual division, but that could be done in the next two phases as well.  Plant cells generally begin constructed the cell wall that will be between the new cells, the cell plate, in anaphase.

Anaphase.
 

Cell plate forming.

Telophase is the stage that puts everything back as it needs to be for the cell or cells to go back to work, so most of what happened in prophase "unhappens" in telophase:  the nuclear envelopes reform around each group of chromosomes;  the chromosomes go from being tightly packaged and visible with a light microscope to being loosely packaged, accessible for transcription, and not visible;  the spindles get disassembled;  the nucleoli get reassembled.  The cell returns to interphase.

Telophase with beginning cytokinesis.

Much of what happens in mitosis also happens in meiosis.  During interphase, DNA gets copied, producing copies of two sets of chromosomes, or four potential sets.  Since the end-product cells will only have one set each, the process will make four cells, and there will two division stages.

In Meiosis 1, prophase is very similar to mitosis with one huge added detail:  as chromosomes are pulled into the equator zone, homologous chromosomes are pulled in next to each other.  As they sit waiting for the other ones to get in place, the molecules may make contact and pieces may swap between homologous pair members.  This is called crossing over.  The chromosomes may exchange equal pieces or unequal pieces.  If a chromosome picks up a much bigger bit than it lost, it will now have extra copies of genes on the chromosome.  If one copy mutates and acquires a new function, the function of the "old" gene doesn't have to be lost, since there's still one of those.  This is one way that organisms can get genetically are functionally more complex as they evolve.  This is also another type of genetic redundancy.

Going into anaphase, the strands don't get separated, the sets do - one set of double-stranded chromosomes goes to one pole, and the second goes to the other pole.  Nuclei reappear and the cells divide.  In egg cell production, the poles are close together and just under the cell membrane, and division leaves one big, nutrient-carrying cell and one cell just big enough to hold a set of double-stranded chromosomes, a polar body.  Polar bodies generally have no other use and die soon after they are made.

Steps of meiosis.

Crossing over.

"New" gene from old one's duplicate.

Meiosis 1.

More on the polar body.

Meiosis 2 starts with two cells, each containing one set of double-stranded chromosomes.  This division proceeds just like a mitosis would, with the strands separating into new cells.  Two cells become four cells, each with one set of "regular" chromosomes.  In egg cells, another polar body would divide off the larger cell from Meiosis 1.

Fertilization, usually involving a sperm nucleus getting into the egg cell, leads to fusion of nuclei, producing a zygote:   the 2N first cell of the offspring.

Another meiosis video.

Fertilization diagram.

In multicelled organisms, the zygote would go through mitosis, become an embryo, and for a while would make a lot of similar cells.  Eventually, different cells would start to access different genes so that they could do different jobs, a process called differentiation.  The cells would carry the same genes, but use different combinations of them.  This is why a genetic disease from an allele for a non-functional protein would be carried by every cell, but only affect some of them.

Blog entry on differentiation.

Genetics and Evolution

The basic rules of evolution by natural selection were worked out long before genetics was understood, but eventually the two areas were merged into what is often called Neodarwinism.

Biologist Richard Dawkins on Neo-Darwinism.

A genome is a term applied to all the the DNA present in something.  An individual has a genome, a population has a genome, a species has a genome.  My genome will be different from your genome because I would carry some alleles that are different from yours, and I might have some mutations you don't (the farther back in time we have a common ancestor, the more different mutations would be there).  A gene pool is all of the alleles in a particular population.

When Darwin talked about adaptations that helped or hurt an individual in its environment, and which could be passed to offspring, he was really talking about traits arising from different alleles.  A more fit individual would have a different mix of alleles to send on to offspring, and each new generation would carry a greater proportion of alleles "good" for their circumstances.  A mutation that produced an allele for a "better" trait would help its owner survive, and they would pass it to offspring, who had a better chance of surviving and passing it to their offspring, so in a few generations it would go from being rare, in just one member of the population, to being more common, being a bigger part of the population's genome.

Evolution is now understood as a change in a population's gene pool over time. 
 

Project to map out the human genome.

How genomes are used to measure evolutionary relationships.

In trying to figure out how gene pools change over time, two statisticians came up with some rules called Hardy-Weinberg Equilibrium.  These stated the conditions under which the pool's alleles would not change, but were obviously connected to what would make them change over time.  These are the needed restrictions:  to stay the same, a population had to have no Natural Selection, Sexual Selection, or Mutations happening, which was no surprise.

The population also had to be very large, because events of pure chance can affect small groups but not really big ones.  The impact of populations size hadn't really been considered, and it was still a long time before it was realized that, since the gene pool had a lot fewer alleles in it, a small population can evolve much faster than a large population.

The remaining factor was known to be important even from Darwin, but this focused attention on it:  the population could not have small groups migrating away or new relative groups migrating in.  An isolated population would change in comparison with other related populations (like an island group differing from the mainland groups).

More on Hardy-Weinberg.

A Hardy-Weinberg Lab Exercise

A few processes turned out to be related to these "new" evolutionary rules:

When a small population starts out, it "sets" the gene pool on which evolution will play.  With a small migrating group, if they move away and become isolated, the gene pool is already different then the original group, and the descendants are working with that limited genetic repertoire.  This is called a founder effect.

If something dramatically shrinks a population, a near-extinction, whatever alleles are left in the survivors is the new gene pool that passes to descendants.  This is called a bottleneck effect.

More on these two effects.

It turns out that the only critical isolation is reproductive isolation - once populations can not pass alleles between them, they can change along separate paths.  There are a few different ways to accomplish this:

Geographic isolation is the best know type - here, some sort of physical barrier separates populations.  This could be a desert, a widening river, mountains, or sea expanses.

Niche isolation (also called ecological isolation) happens when groups in what starts as a single population in the same area begin to specialize in different ways, to occupy different niches or ecological roles.  This might involve slightly different food types, or different locations (such as treetops versus ground-browsing), or different active times (such as day versus night).  This may get the groups reproductively isolated as the groups don't encounter each other as much, but also as groups get specialized, behavior that avoids cross-breeding become advantageous anyway.

Temporal isolation happens when a subgroup becomes reproductively active at a different time than the main population.  If the timing works, the subgroup can become a founder group without ever changing locations.

Behavioral isolation can happen where behaviors factor strongly into reproduction (examples occur in many animal phyla, from birds to spiders);  a subgroup where a different preference arises can separate from the main group.

Chemical isolation is based upon reproductive "choosing" that is strongly based upon chemical compatibility.  Many plants, for example, accept or reject sperm-carrying pollen grains using chemical interactions.  In some species, this isolation could be an immune reaction that similarly rejects sperm in some females.

Mechanical isolation is known from a few species, such as beetles, where the only separating feature between two groups seems to be the way their reproductive anatomy is built:  males from one group cannot couple with females from the other group.
 

More on isolation.

Geographic isolation example.

Niche isolation example.

Temporal isolation example.

Behavioral and chemical isolation at work.

Go On to Next Chapter - Energy in Life Processes

Introduction to Biology - Molecules & Cells.
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