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.
