It’s Professor Dave, let’s take a look at chromosomes.
In biochemistry we learned all about nucleic acids, including DNA.
We learned about how nucleotides polymerize and how two strands of DNA come together to
form a long double helix, with millions of base pairs.
But to go from this to a more complete understanding of all the chromosomes in every one of your
cells is a pretty big leap, so let’s fill in some of the gaps regarding chromosomal
structure and arrangement.
First, we must understand that while we often see pictures of DNA looking like this, DNA
is not just floating around the nucleus in this form.
DNA is typically coiled up to save space, because there is so much of it to store.
DNA strands are wrapped around proteins called histones, and these DNA-histone complexes
are called nucleosomes.
Then, this undergoes further supercoiling until we get chromosomes of the familiar shape.
In a human diploid cell, which is every cell in your body except for reproductive cells,
there are two versions of every chromosome, one maternal and one paternal, which makes
two sets of 23 chromosomes, or 46 in total.
Each chromosome will duplicate through DNA replication to give two identical sister chromatids.
So here we can see a homologous pair of chromosomes, which contain the same genes, but different
alleles for that gene, one from each parent, so these are not precisely identical to one
another.
But each chromosome consists of two identical sister chromatids, which will be pulled apart
during mitosis so that each daughter cell can have a complete set of chromosomes.
When Mendel spoke of genes, it was an abstract concept, as no one knew about DNA at that
time.
But later in the century when microscopes became powerful enough to see chromosomes
and watch mitosis take place, scientists began to see that Mendel had been exactly right,
and they developed the chromosome theory of inheritance.
They realized that the genes we learned about from Mendelian genetics are actually long
stretches of DNA that code for various proteins.
These genes have specific locations on specific chromosomes, and each chromosome in a homologous
pair has the same gene at the same spot.
This new understanding explained all of Mendel’s observations.
In meiosis, homologous pairs of chromosomes are separated, which accounts for the law
of segregation.
Only one allele for a particular gene will show up in a gamete, not both.
And the fact that homologous pairs are arranged randomly during this process accounts for
the law of independent assortment, because if two genes are located on two different
chromosomes, the combination of alleles for those two genes that ends up in a particular
gamete will be totally random as well.
So before DNA structure was fully understood, we knew that chromosomes contained genes.
As we now understand, each chromosome contains hundreds or even thousands of genes.
Even still, genes only comprise around one to one and a half percent of the genome, so
what’s the rest?
In between all the genes is noncoding DNA.
This is the majority of the DNA, which does not code for any proteins.
However, this area still serves a variety of functions, like transcribing RNA’s other
than mRNA, serving as origins of replication, regulating gene expression, and comprising
centromeres as well as telomeres.
These sections, called telomeres, are found at the ends of each chromosome, and they are
sections of DNA where, in humans, the sequence TTAGGG is repeated hundreds of times.
This is because with every round of DNA replication, the enzymes involved can’t quite copy the
last couple bases, so this extra padding is present so that even after many rounds of
replication, the ends haven’t shortened so much that the genetic information present
within an actual gene starts to get eroded away, which would be harmful to a cell.
If this does happen, it is called replicative senescence.
In some cells, an enzyme called telomerase regularly extends the telomeres, which buys
a cell a little more time.
Beyond telomeres, some areas of noncoding DNA are called transposons.
These are sequences that can change position within a genome.
Now that we understand how the genome is packaged, we should discuss a key difference in the
chromosomes of human males and females.
There is a pair of sex chromosomes present in each cell, and for a female these are both
X chromosomes, with the familiar shape.
But for a male, one of these is X and one of these is a Y chromosome, which is much
smaller.
During meiosis, all egg cells get X chromosomes, since that’s all there is in the parent
cells of a female, but sperm cells can end up with either an X or a Y, since they are
both present in diploid cells for the male.
A cell or zygote that inherits two X chromosomes upon fertilization will become a female, and
one that gets an X and a Y will become male, so sex determination is essentially a flip
of a coin.
These two chromosomes are partially homologous, but obviously the Y chromosome is missing
genes that are present on the X chromosome, as the Y is much smaller.
This means that males have only one allele for certain genes where females will have
two.
These are called X-linked genes, because they are present only on the X chromosome and not
the Y.
In such a case, if the singular allele is recessive, a male will express the recessive
phenotype, as there is no dominant allele present to override this.
There are a number of disorders that are attributed to X-linked genes, such as color-blindness
and hemophilia.
We should also note that females, with two X chromosomes, typically have one of these
largely inactivated in each cell, and the inactive one is chosen at random, so some
cells have an active X chromosome that came from the mother, and some from the father.
This results in phenotypes like two colors of fur on female cats, because some of the
cells have an X chromosome active with an allele for one color of fur, and other cells
have the other X chromosome active, which has the other allele, and corresponds to a
different color.
So now we should finally be able to look at a picture of a chromosome and see all the
tiers of structure within, by connecting concepts from biology, biochemistry, and chemistry.
This huge structure, a replicated chromosome consisting of two sister chromatids, is made
of looped domains wrapped around a scaffold.
These looped domains can be unwound to reveal a fiber of nucleosomes, which result when
DNA wraps around histones to form tiny beads.
And we can even zoom in on DNA to reveal a double helical form, the structure of the
nitrogenous bases that dictate base-pairing, all the way down to individual atoms and beyond.
This huge structure contains genes, that when expressed, produce all of the proteins in
your body.
So how does gene expression work, and how is it regulated?
Let’s move forward and learn about this next.