Principles of Inheritance and Variation

Intro to vascular tissues (xylem

& phloem)
Intro to gene expression (central dogma)
How genes in DNA can provide instructions for proteins. The central dogma of molecular biology:
DNA → RNA → protein.

Tissues, organs, & organ systems

Learn about the main tissue types and organ systems of the body and how they work together.

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Key points
 Humans—and other complex multicellular organisms—have systems of
organs that work together, carrying out processes that keep us alive.
 The body has levels of organization that build on each other. Cells make
up tissues, tissues make up organs, and organs make up organ systems.
 The function of an organ system depends on the integrated activity of its
organs. For instance, digestive system organs cooperate to process food.
 The survival of the organism depends on the integrated activity of all the
organ systems, often coordinated by the endocrine and nervous systems.

1. Write your Reflection Paper after going over the four (4) links for today's asynchronous
lessons.
2. Answer the following guide questions:
   - What have you mastered  now after learning these topics? ("mastered" means you knew it
already but have known better today)
   - What have you learned  just today? (share something new you have known from the lessons)
   - Which concepts are you still interested to learn more  about?

How can we study inheritance?

When spending time with your own family, friends, and neighbors, you may
have noticed that many traits run in families. For instance, members of a
family may share similar facial features, hair color (like the brother and sister
below), or a predisposition to health problems such as diabetes.
Characteristics that run in families often have a genetic basis, meaning that
they depend on genetic information a person inherits from his or her parents.
 Image of a brother and sister who both have distinctive reddish hair.
Image credit "Brother, sister, portrait, russet," by Adina Voicu (CC0, public domain).

What if you wanted to figure out how genetic information is transmitted

between generations? For instance, you might be curious how traits can
"skip" a generation, or why one child in a family may suffer from a genetic
disease while another does not. How could you go about asking these kinds
of questions scientifically?

An obvious first idea would be to study human inheritance patterns directly,

but that turns out to be a tricky proposition (see the pop-up below for details).
In this article, we'll see how a nineteenth-century monk named Gregor
Mendel instead uncovered the key principles of inheritance using a simple,
familiar system: the pea plant. 
[Why didn't Mendel study humans?]

The monk in the garden: Gregor Mendel

Johann Gregor Mendel (1822–1884), often called the “father of genetics,”
was a teacher, lifelong learner, scientist, and man of faith. It would be fair to
say that Mendel had a lot of grit: he persevered through difficult
circumstances to make some of the most important discoveries in biology.
 Portrait of Gregor Mendel.
Image credit: "Mendel's experiments and the laws of probability: Figure 1," by OpenStax College, Biology
(CC BY 3.0).

As a young man, Mendel had difficulty paying for his education due to his
family's limited means, and he also suffered bouts of physical illness and
depression; still, he persevered to graduate from high school and, later,
university^11start superscript, 1, end superscript. After finishing university,
he joined the Augustinian Abbey of St. Thomas in Brno, in what is now the
Czech Republic. At the time, the monastery was the cultural and intellectual
hub of the region, and Mendel was immediately exposed to new teachings
and ideas^11start superscript, 1, end superscript.

His decision to join the order (against the wishes of his father, who expected
him to carry on the family farm) appears to have been motivated in part by a
desire to continue his education and pursue his scientific interests^22squared.
Supported by the monastery, he taught physics, botany, and natural science
courses at the secondary and university levels.

Research on heredity
In 1856, Mendel began a decade-long research project to investigate patterns
of inheritance. Although he began his research using mice, he later switched
to honeybees and plants, ultimately settling on garden peas as his primary
model system^22squared. A model system is an organism that makes it easy
for a researcher to investigate a particular scientific question, such as how
traits are inherited. By studying a model system, researchers can learn general
principles that apply to other, harder-to-study organisms or biological
systems, such as humans.

Mendel studied the inheritance of seven different features in peas, including

height, flower color, seed color, and seed shape. To do so, he first established
pea lines with two different forms of a feature, such as tall vs. short height.
He grew these lines for generations until they were pure-breeding (always
produced offspring identical to the parent), then bred them to each other and
observed how the traits were inherited.

In addition to recording how the plants in each generation looked, Mendel

counted the exact number of plants that showed each trait. Strikingly, he
found very similar patterns of inheritance for all seven features he studied:
 One form of a feature, such as tall, always concealed the other form, such as
short, in the first generation after the cross. Mendel called the visible form
the dominant trait and the hidden form the recessive trait.
 In the second generation, after plants were allowed to self-fertilize (pollinate
themselves), the hidden form of the trait reappeared in a minority of the
plants. Specifically, there were always about 333 plants that showed the
dominant trait (e.g., tall) for every 111 plant that showed the recessive trait
(e.g., short), making a 3:13:13, colon, 1 ratio.
 Mendel also found that the features were inherited independently: one
feature, such as plant height, did not influence inheritance of other features,
such as flower color or seed shape.

Representation of results from one of Mendel's experiments. When a tall and

short plant are crossed, all of the offspring are tall. If the offspring self-
 fertilize, they produce tall and short plants in a ratio of 3:1 in the next
generation. Mendel's actual counts were 787 tall:277 short plants in this
generation (2.84:1 ratio).
_Image modified from "Mendel seven characters," by Mariana Ruiz Villareal (public domain)._

In 1865, Mendel presented the results of his experiments with nearly 30,000
pea plants to the local Natural History Society. Based on the patterns he
observed, the counting data he collected, and a mathematical analysis of his
results, Mendel proposed a model of inheritance in which:

 Characteristics such as flower color, plant height, and seed shape were
controlled by pairs of heritable factors that came in different versions.
 One version of a factor (the dominant form) could mask the presence of
another version (the recessive form).
 The two paired factors separated during gamete production, such that each
gamete (sperm or egg) randomly received just one factor.
 The factors controlling different characteristics were inherited independently
of one another.
We'll take a closer look at how Mendel reached these conclusions in the
articles on the law of segregation and the law of independent assortment. In
1866, Mendel published his observations and his model of inheritance, under
the title Experiments in Plant Hybridization^{3,4}3,4start superscript, 3,
comma, 4, end superscript, in the Proceedings of the Natural History Society
of Brünn.

Scientific legacy
Mendel's work went largely unnoticed by the scientific community during his
lifetime. How could this have been the case?
In part, Mendel's contemporaries failed to recognize the importance of his
work because his findings went against prevailing (popular) ideas about
inheritance. In addition, although we now see Mendel's mathematical
approach to biology as innovative and pioneering, it was new, unfamiliar, and
perhaps confusing or unintuitive to other biologists of the time^55start
superscript, 5, end superscript.

In the mid-1800s, when Mendel was doing his experiments, most biologists
subscribed to the idea of blending inheritance. Blending inheritance wasn't a
formal, scientific hypothesis, but rather, a general model in which inheritance
involved the permanent blending of parents' characteristics in their offspring
(producing offspring with an intermediate form of a characteristic)^66start
superscript, 6, end superscript. The blending model fit well with some
observations of human inheritance: for instance, children often look a bit like
both of their parents.

But the blending model could not explain why Mendel crossed a tall and a
short pea plant and got only tall plants, or why self-fertilization of one of
those tall plants would produce a 3:13:13, colon, 1 ratio of tall to short plants
in the next generation. Instead, if the blending model were correct, a tall plant
crossed with a short plant should produce a medium plant, which would go
on to produce more medium plants (see below).
Image comparing the predictions of the blending model with Mendel's actual
results for a cross between a tall pea plant and a short pea plant.

The blending model predicts that all the offspring from the cross should be of
medium height, and that if those offspring self-fertilize, all the plants in the
next generation will also be of medium height.

Mendel instead observed that all the offspring of the cross were tall, and that
when they self-fertilized, they produced tall and short plants in a ratio of 3:1.
_Image modified from "Mendel seven characters," by Mariana Ruiz Villareal (public domain)._

As it turns out, both pea plant height and human height (along with many
other characteristics in a wide range of organisms) are controlled by pairs of
heritable factors that come in distinctive versions, just as Mendel proposed.
In humans, however, there are many different factors (genes) that contribute
fractionally to height and vary among individuals. This makes it difficult to
see the contribution of any one factor and produces inheritance patterns that
can resemble blending. In Mendel's experiments, in contrast, there was just
one factor that differed between the tall and short pea plants, allowing
Mendel to clearly see the underlying pattern of inheritance.

In 1868, Mendel became abbot of his monastery and largely set aside his
scientific pursuits in favor of his pastoral duties. He was not recognized for
his extraordinary scientific contributions during his lifetime. In fact, it was
not until around 1900 that his work was rediscovered, reproduced, and
revitalized. Its rediscoverers were biologists on the brink of discovering the
chromosomal basis of heredity – that is, about to realize that Mendel's
“heritable factors” were carried on chromosomes.
Mendel’s model system: The pea plant
Mendel carried out his key experiments using the garden pea, Pisum sativum,
as a model system. Pea plants make a convenient system for studies of
inheritance, and they are still studied by some geneticists today.

Useful features of peas include their rapid life cycle and the production of
lots and lots of seeds. Pea plants also typically self-fertilize, meaning that the
same plant makes both the sperm and the egg that come together in
fertilization. Mendel took advantage of this property to produce true-
breeding pea lines: he self-fertilized and selected peas for many generations
until he got lines that consistently made offspring identical to the parent (e.g.,
always short).

Pea plants are also easy to cross, or mate in a controlled way. This is done by
transferring pollen from the anthers (male parts) of a pea plant of one variety
to the carpel (female part) of a mature pea plant of a different variety. To
prevent the receiving plant from self-fertilizing, Mendel painstakingly
removed all of the immature anthers from the plant’s flowers before the
cross.

Diagram of pea flowers, showing how a cross is performed. First, a flower on

the female parent is emasculated, meaning that the male parts (anthers) are
removed with forceps or scissors. Then, pollen is collected from a flower on
 the male parent plant using a paintbrush. The pollen is dabbed onto the
female part (carpel) of the female parent flower that was previously
emasculated.
Image based on similar illustration from Reece et al.^{7}7start superscript, 7, end superscript

Because peas were so easy to work with and prolific in seed production,
Mendel could perform many crosses and examine many individual plants,
making sure that his results were consistent (not just a fluke) and accurate
(based on many data points).

Mendel’s experimental setup

Once Mendel had established true-breeding pea lines with different traits for
one or more features of interest (such as tall vs. short height), he began to
investigate how the traits were inherited by carrying out a series of crosses.

First, he crossed one true-breeding parent to another. The plants used in this
initial cross are called the \text PPstart text, P, end text generation, or
parental generation.

Mendel collected the seeds from the \text PPstart text, P, end text generation
cross and grew them up. These offspring were called the \text F_1F1start
text, F, end text, start subscript, 1, end subscript generation, short for first
filial generation. (Filius means “son” in Latin, so this name is slightly less
weird than it seems!)

Once Mendel examined the \text F_1F1start text, F, end text, start subscript,
1, end subscript plants and recorded their traits, he let them self-fertilize
naturally, producing lots of seeds. He then collected and grew the seeds from
the \text F_1F1start text, F, end text, start subscript, 1, end subscript plants to
produce an \text F_2F2start text, F, end text, start subscript, 2, end
subscript generation, or second filial generation. Again, he carefully
examined the plants and recorded their traits.
 Diagram of a cross between a tall plant and a short plant, labeling the P, F1,
and F2 generations.
_Image modified from "Mendel seven characters," by Mariana Ruiz Villareal (public domain)._

Mendel's experiments extended beyond the \text F_2F2start text, F, end text,

start subscript, 2, end subscript generation to \text F_3F3start text, F, end text,
start subscript, 3, end subscript, \text F_4F4start text, F, end text, start
subscript, 4, end subscript, and later generations, but his model of inheritance
was based mostly on the first three generations (\text PPstart text, P, end
text, \text F_1F1start text, F, end text, start subscript, 1, end subscript, and \
text F_2F2start text, F, end text, start subscript, 2, end subscript).

Mendel didn’t just record what his plants looked like in each generation (e.g.,
tall vs. short). Instead, he counted exactly how many plants with each trait
were present. This may sound tedious, but by recording numbers and thinking
mathematically, Mendel made discoveries that eluded famous scientists of his
time (such as Charles Darwin, who carried out similar experiments but didn’t
grasp the significance of his results)^{5}5start superscript, 5, end superscript.

You can use the links below to learn more about Mendel's laws of
inheritance:

 The law of segregation, describing how individual traits are inherited.

 The law of independent assortment, describing how two or more traits are
inherited relative to one another.
[Attribution and references]
Next article
Key terms
Term Meaning

Genetics The study of biological inheritance

Trait A specific characteristic of an individual

Gene A unit of heredity that is passed from parent to offspring

Allele One of different forms of a gene

Genotype The genetic makeup of an organism (ex: TT)

Phenotype The physical characteristics of an organism (ex: tall)

Dominant Allele that is phenotypically expressed over another

allele allele

Recessive Allele that is only expressed in absence of a dominant

allele allele

Homozygous Having two identical alleles for a particular gene

Heterozygous Having two different alleles for a particular gene

Diagram that can be used to predict the genotypes and

Punnett square phenotypes resulting from a genetic cross
Mendelian inheritance
Gregor Mendel's principles of heredity, observed through patterns of
inheritance in pea plants, form the basis of modern genetics.

Mendel proposed that traits were specified by "heritable elements"

called genes. Genes come in different versions, or alleles, with dominant
alleles being expressed over recessive alleles. Recessive alleles are only
expressed when no dominant allele is present.

In most sexually reproducing organisms, each individual has two alleles for
each gene (one from each parent). This pair of alleles is called
a genotype and determines the organism's appearance, or phenotype.
Mendel's laws

Table showing how genes exchange according to segregation or independent

assortment during meiosis and how this translates into the Mendel's Laws.
Laws of segregation and independent assortment. Image modified from Wikimedia, Public domain

When an organism makes gametes, each gamete receives just one gene copy,
which is selected randomly. This is known as the law of segregation.
Mendel's second law is the law of independent assortment, which states that
the alleles for one gene sort into gametes independently of the alleles of
another gene.

Punnett squares and probability

A Punnett square can be used to predict genotype and phenotypes of
offspring from genetic crosses. A single-gene, or monohybrid cross is
pictured below.
 This illustration shows a monohybrid cross. In the P generation, one parent
has a dominant yellow phenotype and the genotype YY, and the other parent
has the recessive green phenotype and the genotype yy. Each parent produces
one kind of gamete, resulting in an F{1} generation with a dominant yellow
phenotype and the genotype Yy. Self-pollination of the F{1} generation
results in an F_{2} generation with a 3 to 1 ratio of yellow to green peas. One
 out of three of the yellow pea plants has a dominant genotype of YY, and 2
out of 3 has the heterozygous genotype Yy. The homozygous recessive plant
has the green phenotype and the genotype yy.
Monohybrid Punnett square. Image modified from OpenStax, CC BY 4.0

A test cross can be used to determine whether an organism with a dominant

phenotype is homozygous or heterozygous.
In a test cross, a parent with a dominant phenotype but unknown genotype is
crossed with a recessive parent. If the parent with the unknown genotype is
homozygous dominant, all the resulting offspring will have at least one
dominant allele. If the parent with the unknown genotype is heterozygous, 50
 percent of the offspring will inherit a recessive allele from both parents and
will have the recessive phenotype.
Example test cross. Image credit: OpenStax, CC BY 4.0

Punnett squares can be used for a two-gene crosses, or dihybrid crosses by

following the same basic rules as for a monohybrid cross. However, since
there are now more gamete types, there must also be more squares in the
table.

Illustration of the hypothesis that the seed color and seed shape genes assort
independently.
In this diagram, the Y and R alleles of the yellow, round parent and the y and
r alleles of the green, wrinkled parent are not inherited as units. Instead, the
alleles of the two genes are inherited as independent units.

P generation: A yellow, round plant (YYRR) is crossed with a green,

wrinkled plant (yyrr). Each parental generation can produce only one type of
gamete, YR or yr.

F1 generation: The F1 dihybrid seeds are yellow and round, with a genotype
of YyRr. The F1 plants can produce four different types of gametes: YR, Yr,
yR, and yr. We can predict the genotypes of the F2 plants by placing these
gametes along the top and side axes of a 4X4 Punnett square and filling in the
boxes to represent fertilization events.

F2 generation: Completion of the Punnett square predicts four different

phenotypic classes of offspring, yellow/round, yellow/wrinkled, green/round,
and green/wrinkled, in a ratio of 9:3:3:1. This is the prediction of the model in
which the seed shape and seed color genes assort independently.

Punnett square:

YR Yr yR yr

Y YYR YYR YyR YyR

R R r R r

YYR
Yr r YYrr YyRr Yyrr

YyR YyR yyR

yR R r R yyRr
 YR Yr yR yr

yr YyRr Yyrr yyRr yyrr

Plain text = yellow, round phenotype Italic text = yellow, wrinkled

phenotype Bold text = green, round phenotype Bold, italic text = green,
wrinkled phenotype
Dihybrid cross. Image credit: "OpenStax," CC BY 4.0.

Probabilities in genetics
The two probability rules that are most relevant to Punnett squares are
the product rule and the sum rule.

The product rule states that the probability of two (or more) independent
events occurring together can be calculated by multiplying the individual
probabilities of the events.

Illustration of how a Punnett square can represent the product rule.

Punnett square:
 A a

A A
A A a

a Aa aa

There's a 1/2 chance of getting an a allele from the male parent,

corresponding to the rightmost column of the Punnett square. Similarly,
there's a 1/2 chance of getting an a allele from the maternal parent,
corresponding to the bottommost row of the Punnett square. The intersect of
these the row and column, corresponding to the bottom right box of the table,
represents the probability of getting an a allele from the maternal parent and
the paternal parent (1 out of 4 boxes in the Punnett square, or a 1/4 chance).
Example of the product rule using a Punnett square.

In some genetics problems, you may need to calculate the probability that any
one of several events will occur. In this case, you’ll need to apply another
rule of probability, the sum rule. According to the sum rule, the probability
that any of several mutually exclusive events will occur is equal to the sum of
the events’ individual probabilities.
 Illustration of how a Punnett square can represent the sum rule.

Punnett square:

A a

A A
A A a

a Aa aa

The bolded boxes represent events that result in a dominant phenotype (AA

or AA genotype). In one, an A sperm combines with an A egg. In another, an
A sperm combines with an a egg, and in a third, an a sperm combines with an
A egg. Each event has a 1/4 chance of happening (1 out of 4 boxes in the
Punnett square). The chance that any of these three events will occur is
1/4+1/4+1/4 = 3/4.
Example of the sum rule using a Punnett square.

Common mistakes and misconceptions

 Dominant traits are not always the most common. Some people may think
that dominant trait is the most likely to be found in the population, but the
term "dominant" only refers to the fact that the allele is expressed over
another allele. An example of this is Huntington's disease. Even though
Huntington's is caused by a dominant allele, it only affects about 30,000
people in the United States^11start superscript, 1, end superscript.
 Traits are not always the product of a single gene. For example, there are
at least 3 different genes that are associated with eye color in humans. In
 addition, there are sometimes more than two alleles for each gene. For
example, there are 3 different alleles of one gene determine coat color of cats.
Next video

Go to lesson page | X-linked

inheritanceX-linked inheritance

Key points:
 In humans and other mammals, biological sex is determined by a pair of sex
chromosomes: XY in males and XX in females.
 Genes on the X chromosome are said to be X-linked. X-linked genes have
distinctive inheritance patterns because they are present in different numbers
in females (XX) and males (XY).
 X-linked human genetic disorders are much more common in males than in
females due to the X-linked inheritance pattern.

Introduction
If you’re a human being (which seems like a good bet!), most of your
chromosomes come in homologous pairs. The two chromosomes of a
homologous pair contain the same basic information – that is, the same genes
in the same order – but may carry different versions of those genes.

Are all of your chromosomes organized in homologous pairs? The answer

depends on whether you’re (chromosomally) male.
 Image of a human karyotype, showing the 44 autosomes in matching pairs
and 2 dissimilar sex chromosomes (X and Y),
Image modified from "Karyotype," by Can H. (CC BY 2.0).

 A human male has two sex chromosomes, the X and the Y. Unlike

the 444444 autosomes (non-sex chromosomes), the X and Y don’t carry the
same genes and aren’t considered homologous.
 Instead of an X and a Y, a human female has two X chromosomes. These X
chromosomes do form a bona fide homologous pair.
Because sex chromosomes don’t always come in homologous pairs, the genes
they carry show unique, distinctive patterns of inheritance.
Sex chromosomes in humans
Human X and Y chromosomes determine the biological sex of a person, with
XX specifying female and XY specifying male. Although the Y chromosome
contains a small region of similarity to the X chromosome so that they can
pair during meiosis, the Y chromosome is much shorter and contains many
fewer genes.

To put some numbers to it, the X chromosome has about 800-

900800−900800, minus, 900 protein-coding genes with a wide variety of
functions, while the Y chromosome has just 60-7060−7060, minus,
70 protein-coding genes, about half of which are active only in the testes
(sperm-producing organs)^{1,2,3,4}1,2,3,4start superscript, 1, comma, 2,
comma, 3, comma, 4, end superscript.
Diagram of the human X and Y chromosomes. The X is much larger than the
Y. The X and Y have small regions of homology at both tips, which allow
pairing of the chromosomes during meiosis. The SRY gene is found on the Y
chromosome, near the tip, just below the region of homology with the X
chromosome.
Image based on ideograms from the Genome Decoration Page, maintained by the U.S. NCBI.

The human Y chromosome plays a key role in determining the sex of a

developing embryo. This is mostly due to a gene called SRY (“sex-
determining region of Y”). SRY is found on the Y chromosome and encodes a
protein that turns on other genes required for male development^{5,6}5,6start
superscript, 5, comma, 6, end superscript.
 XX embryos don't have SRY, so they develop as female.
 XY embryos do have SRY, so they develop as male.
In rare cases, errors during meiosis may transfer SRY from the Y
chromosome to the X chromosome. If an SRY-bearing X chromosome
fertilizes a normal egg, it will produce a chromosomally female (XX) embryo
that develops as a male^77start superscript, 7, end superscript. If an SRY-
deficient Y chromosome fertilizes a normal egg, it will produce a
chromosomally male embryo (XY) that develops as a female^88start
superscript, 8, end superscript.
[Do all species with X and Y chromosomes have the SRY gene?]

X-linked genes
When a gene is present on the X chromosome, but not on the Y chromosome,
it is said to be X-linked. X-linked genes have different inheritance patterns
than genes on non-sex chromosomes (autosomes). That's because these genes
are present in different copy numbers in males and females. 
[What about genes on the Y?]

Since a female has two X chromosomes, she will have two copies of each X-
linked gene. For instance, in the fruit fly Drosophila (which, like humans, has
XX females and XY males), there is a eye color gene called white that's
found on the X chromosome, and a female fly will have two copies of this
gene. If the gene comes in two different alleles, such as \text X^WXWstart
text, X, end text, start superscript, W, end superscript(dominant, normal red
eyes) and \text X^wXwstart text, X, end text, start superscript, w, end
superscript (recessive, white eyes), the female fly may have any of three
genotypes: \text X^WXWstart text, X, end text, start superscript, W, end
superscript\text X^WXWstart text, X, end text, start superscript, W, end
superscript (red eyes), \text X^WXWstart text, X, end text, start superscript,
W, end superscript\text X^wXwstart text, X, end text, start superscript, w, end
superscript (red eyes), and \text X^wXwstart text, X, end text, start
superscript, w, end superscript\text X^wXwstart text, X, end text, start
superscript, w, end superscript (white eyes).

A male has different genotype possibilities than a female. Since he has only
one X chromosome (paired with a Y), he will have only one copy of any X-
linked genes. For instance, in the fly eye color example, the two genotypes a
male can have are \text X^W\text YXWYstart text, X, end text, start
superscript, W, end superscript, start text, Y, end text (red eyes) and \text
X^w\text YXwYstart text, X, end text, start superscript, w, end superscript, start
text, Y, end text (white eyes). Whatever allele the male fly inherits for an X-
linked gene will determine his appearance, because he has no other gene copy
—even if the allele is recessive in females. Rather than homozygous or
heterozygous, males are said to be hemizygous for X-linked genes.

We can see how sex linkage affects inheritance patterns by considering a

cross between two flies, a white-eyed female (\text X^w\text X^wXwXwstart
text, X, end text, start superscript, w, end superscript, start text, X, end text,
start superscript, w, end superscript) and a red-eyed male (\text X^W\text
YXWYstart text, X, end text, start superscript, W, end superscript, start text, Y,
end text). If this gene were on a non-sex chromosome, or autosome, we
would expect all of the offspring to be red-eyed, because the red allele is
dominant to the white allele. What we actually see is the following:
This illustration shows a Punnett square analysis of fruit fly eye color, which
is a sex-linked trait. A red-eyed male fruit fly with the genotype X^{W}Y is
crossed with a white-eyed female fruit fly with the genotype X^{w}X^{w}.
All of the female offspring acquire a dominant W allele from the father and a
recessive w allele from the mother, and are therefore heterozygous dominant
with red eye color. All of the male offspring acquire a recessive w allele from
the mother and a Y chromosome from the father and are therefore
hemizygous recessive with white eye color.
Image credit: "Characteristics and traits: Figure 10," by OpenStax College, Biology, CC BY 4.0

However, because the gene is X-linked, and because it was the female parent
who had the recessive phenotype (white eyes), all the male offspring—who
get their only X from their mother—have white eyes (\text X^w\text
YXwYstart text, X, end text, start superscript, w, end superscript, start text, Y,
end text). All the female offspring have red eyes because they received two
Xs, with the \text X^WXWstart text, X, end text, start superscript, W, end
superscript from the father concealing the recessive \text X^wXwstart text, X,
end text, start superscript, w, end superscript from the mother.

X-linked genetic disorders

The same principles we see at work in fruit flies can be applied to human
genetics. In humans, the alleles for certain conditions (including some forms
of color blindness, hemophilia, and muscular dystrophy) are X-linked. These
diseases are much more common in men than they are in women due to their
X-linked inheritance pattern.

Why is this the case? Let's explore this using an example in which a mother is
heterozygous for a disease-causing allele. Women who are heterozygous for
disease alleles are said to be carriers, and they usually don't display any
symptoms themselves. Sons of these women have a 50 \%50%50,
percent chance of getting the disorder, but daughters have little chance of
getting the disorder (unless the father also has it), and will instead have
a 50\%50%50, percent chance of being carriers.
 A diagram shows an unaffected father with a dominant allele and an
unaffected carrier mother with an x-linked recessive allele. Four figures of
offspring are shown representing the various resulting genetic combinations:
unaffected son, unaffected daughter, affected son, and unaffected carrier
daughter.
Image credit: "Characteristics and traits: Figure 10," by OpenStax College, Biology, CC BY 4.0
Why is this the case? Recessive X-linked traits appear more often in males
than females because, if a male receives a "bad" allele from his mother, he
has no chance of getting a "good" allele from his father (who provides a Y) to
hide the bad one. Females, on the other hand, will often receive a normal
allele from their fathers, preventing the disease allele from being expressed.

Case study: Hemophilia

Let's look at a Punnett square example using an X-linked human disorder:
hemophilia, a recessive condition in which a person's blood does not clot
properly^{13}13start superscript, 13, end superscript. A person with
hemophilia may have severe, even life-threatening, bleeding from just a small
cut.

Hemophilia is caused by a mutation in either of two genes, both of which are

located on the X chromosome. Both genes encode proteins that help blood
clot^{14}14start superscript, 14, end superscript. Let's focus on just one of
these genes, calling the functional allele \text X^HXHstart text, X, end text,
start superscript, H, end superscript and the disease allele \text X^hXhstart
text, X, end text, start superscript, h, end superscript.

In our example, a woman who is heterozygous for normal and hemophilia

alleles (\text X^H \text X^hXHXhstart text, X, end text, start superscript, H,
end superscript, start text, X, end text, start superscript, h, end superscript)
has children with a man who is hemizygous for the normal form (\text X^H\
text YXHYstart text, X, end text, start superscript, H, end superscript, start text,
Y, end text). Both parents have normal blood clotting, but the mother is a
carrier. What is the chance of their sons and daughters having hemophilia?
 Punnett square showing the potential genotypes of children produced by a
father with normal clotting (\text X^H\text YXHYstart text, X, end text, start
superscript, H, end superscript, start text, Y, end text) and a heterozygous
carrier mother (\text X^H\text X^hXHXhstart text, X, end text, start superscript,
H, end superscript, start text, X, end text, start superscript, h, end superscript).

\text X^HXHstart text, X,

end text, start
superscript, H, end \text YYstart text, Y,
superscript end text

\text X^HXHstart \text X^H\text \text X^H\text

text, X, end text, X^HXHXHstart text, X, end YXHYstart text, X, end
start superscript, text, start superscript, H, text, start superscript,
H, end superscript end superscript, start text, H, end superscript,
X, end text, start start text, Y, end text
superscript, H, end
 \text X^HXHstart text, X,
end text, start
superscript, H, end \text YYstart text, Y,
superscript end text

superscript

\text X^H\text
X^hXHXhstart text, X, end
text, start superscript, H, \text X^h\text
\text X^hXhstart end superscript, start text, YXhYstart text, X, end
text, X, end text, X, end text, start text, start superscript,
start superscript, superscript, h, end h, end superscript,
h, end superscript superscript start text, Y, end text

All daughters (\text X^H\text X^HXHXHstart text, X, end text, start superscript,
H, end superscript, start text, X, end text, start superscript, H, end
superscript, \text X^H\text X^hXHXhstart text, X, end text, start superscript, H,
end superscript, start text, X, end text, start superscript, h, end superscript)
have normal blood clotting because they have at least one \text X^HXHstart
text, X, end text, start superscript, H, end superscript alelle. 1/21/21, slash,
2 of the daughters are carriers, while the other half are homozygous for the \
text X^HXHstart text, X, end text, start superscript, H, end superscript allele.

1/21/21, slash, 2 of sons are \text X^H\text YXHYstart text, X, end text, start
superscript, H, end superscript, start text, Y, end text and have normal blood
clotting.

1/21/21, slash, 2 of sons are \text X^h\text YXhYstart text, X, end text, start
superscript, h, end superscript, start text, Y, end text and have hemophilia.
 Since the mother is a carrier, she will pass on the hemophilia allele (\text
X^hXhstart text, X, end text, start superscript, h, end superscript) on to half of
her children, both boys and girls.

 None of the daughters will have hemophilia (zero chance of the disorder).
That's because, in order to have the disorder, they must get a \text X^hXhstart
text, X, end text, start superscript, h, end superscript allele from both their
mother and their father. There is 000 chance of the daughters getting an \text
X^hXhstart text, X, end text, start superscript, h, end superscript allele from
their father, so their overall chance of having hemophilia is zero.
 The sons get a Y from their father instead of an X, so their only copy of the
blood clotting gene comes from their mother. The mother is heterozygous, so
half of the sons, on average, will get an \text X^hXhstart text, X, end text,
start superscript, h, end superscript allele and have hemophilia (1/21/21,
slash, 2 chance of the disorder).
[Can a woman ever have hemophilia?]

Check your understanding

1. Which of the following pairs of parents is most likely to produce a
daughter with hemophilia?
Choose 1 answer:

Choose 1 answer:

o
(Choice A)

A hemophiliac mother and an unaffected father

o
 (Choice B)

A carrier mother and an unaffected father

o
(Choice C)

A carrier mother and a hemophiliac father

o
(Choice D)

An unaffected, non-carrier mother and a hemophiliac father

[Hint]

Check

[Attribution and references]

Next video

Go to lesson page | X-inactivationX-

inactivation

Introduction
Having extra or missing chromosomes is not usually a good thing. In fact, for
most chromosomes, having an extra or missing copy is lethal to humans
(causing an embryo to die early in development).
Yet, human females have two X chromosomes (XX), while human males
have just one (XY). Why doesn't it cause problems for men to have just one
copy of the X chromosome, while women have two?

X-inactivation
As it turns out, the level of gene activity produced by a single X chromosome
is the normal "dosage" for a human. Men have this dosage because, well, they
only have one X chromosome! Women have the same dosage for a different
reason: they shut down one of their two X chromosomes in a process called
X-inactivation.

In X-inactivation, an X chromosome is compacted (or, as my intro bio

professor liked to say, "crumpled up into a ball"), to make a small, dense
structure called a Barr body. Most of the genes on the Barr body are
inactive, meaning that they are not transcribed. The process of X-inactivation
was discovered by the British geneticist Mary F. Lyon and is sometimes
called lyonization in her honor^{1}1start superscript, 1, end superscript.
 Photograph of Mary F. Lyon, discoverer of X-inactivation.
_Image modified from "Photo of an English geneticist, Mary Frances Lyon," by Jane Gitschier (CC BY 2.5)._

A woman has two X chromosomes, one from each parent. Which one will
she inactivate? X-inactivation is a random process that happens separately in
individual cells during embryonic development. One cell might shut down
the paternal X, while its next-door neighbor might shut down the maternal X
instead. All the cells descended from each of these original cells will
maintain the same pattern of X-inactivation.

Interesting note: if you were a kangaroo, what I just said would not be true!
In kangaroos and other marsupials, it is always the paternal X chromosome
that undergoes X-inactivation^22squared.
X-inactivation example: Calico cat
A classic example of X-inactivation is seen in cats. If a female cat is
heterozygous for black and tan alleles of a coat color gene found on the X,
she will inactivate her two Xs (and thus, the two alleles of the coat color
gene) at random in different cells during development.

The result of is a tortoiseshell coat pattern, made up of alternating patches of

black and tan fur. The black patches come from groups of cells in which the
X with the black allele is active, while the tan patches come from cells in
which the X with the tan allele is active.

Image of a tortoiseshell cat, illustrating the X-inactivation processes

responsible for the different patches of color on its coat. The cat has a mix of
black and tan patches of fur, some small and some large. The cat's genotype
is \text X^O\text X^oXOXostart text, X, end text, start superscript, O, end
 superscript, start text, X, end text, start superscript, o, end superscript, where
the large O stands for orange and the small o stands for black.

 The orange patch is made up of cells in which the X with the orange allele (\
text X^OXOstart text, X, end text, start superscript, O, end superscript) is
active, while the X with the black allele (\text X^oXostart text, X, end text,
start superscript, o, end superscript) is compacted into a Barr body.
 The black patch is made up of cells in which the X with the black allele (\text
X^oXostart text, X, end text, start superscript, o, end superscript) is active,
while the X with the orange allele (\text X^OXOstart text, X, end text, start
superscript, O, end superscript) is compacted into a Barr body.
_Image modified from “6-year old tortoiseshell cat," by Michael Bodega (public domain)._

Although it's rarely as easy to see as in the case of the tortoiseshell cat,
human females are also "mosaic" for any genes that are present in different
alleles on their two X chromosomes.
[If that's true, why don't female carriers show X-linked disorders?]

Sex chromosome aneuploidies

When an organism has an extra or missing copy of a chromosome, it is said
to be aneuploid. Aneuploidies involving autosomes (non-sex chromosomes),
especially large ones, are usually so harmful to development that an
aneuploid embryo can't survive to birth.

Aneuploidies of X chromosomes, however, tend to be much less harmful,

despite the fact that the X is a large chromosome. This is mostly thanks to X
inactivation. Although the purpose of the X-inactivation system is to shut
down the second X of an XX female, it can also do a pretty good job of
shutting down more X chromosomes if they are present.

Examples of X chromosome aneuploidies include:

 Triple X syndrome, in which a woman has an XXX genotype, which occurs
in about 111 out of every 1,1,1, comma000000000 female newborns^{4}4start
superscript, 4, end superscript. Women with an XXX genotype have female
sex characteristics and are fertile (able to have children). In some cases, triple
X syndrome may be associated with learning difficulties, late development of
motor skills in infants, and problems with muscle tone^{4}4start superscript,
4, end superscript.
 Klinefelter syndrome, in which males have an extra X chromosome, leading
to a genotype of XXY. (In rarer cases, Klinefelter syndrome can involve
several extra Xs, leading to an XXXY or XXXXY genotype.) Affected men
may be infertile or develop less dense body and facial hair than other men.
Klinefelter syndrome is thought to affect 111 out of
every 500500500 to 1,1,1, comma000000000 male newborns^{5}5start
superscript, 5, end superscript.
Like females, XXY males with Klinefelter syndrome will convert one X to a
Barr body in each cell. Triple X females (as well as Klinefelter males with
more than two X chromosomes) neutralize their extra Xs by forming
additional Barr bodies. For example, there would be two Barr bodies in a cell
from an XXX female or XXXY male.
 Diagram showing sex chromosomes and Barr body formation in human
individuals with different sex chromosome genotypes.

XX female: one active X, one Barr body. XY male: one active X, one Y, no
Barr body. XXY male (Klinefelter syndrome): one active X, one Y, one Barr
body. XXX female (triple X syndrome): one active X, two Barr bodies.

in Turner syndrome, a woman lacks part or all of one of her X

chromosomes (leaving her with just one functional X). People with this
disorder develop as females, but often have short stature and may exhibit
symptoms like infertility and learning difficulties. Turner syndrome is
thought to occur in about 111 out of every 2,2,2, comma500500500 female
births^66start superscript, 6, end superscript. It has relatively mild effects
because humans normally have only one X active in the cells of their body
anyway.
 Check your understanding
Although most tortoiseshell cats are female, a litter of kittens will
occasionally contain a male tortoiseshell. Which of the following can
explain tortoiseshell coat color in a male kitten?
Choose 1 answer:

Choose 1 answer:


(Choice A)

The male kitten has an extra Y chromosome


(Choice B)

The male kitten has an extra X chromosome


(Choice C)

The male kitten has no X chromosome


(Choice D)

The male kitten cannot carry out X-inactivation

[Hint]

Check

[Attribution and references]

Next video
Go to lesson page | Pedigrees
reviewPedigrees review

Key terms
Term Meaning

Chart that shows the presence or absence of a trait

Pedigree within a family across generations

Genotype The genetic makeup of an organism (ex: TT)

Phenotype The physical characteristics of an organism (ex: tall)

Dominant Allele that is phenotypically expressed over another

allele allele

Recessive Allele that is only expressed in absence of a dominant

allele allele

Trait that is located on an autosome (non-sex

Autosomal trait chromosome)

Sex-linked trait Trait that is located on one of the two sex chromosomes

Homozygous Having two identical alleles for a particular gene

Heterozygous Having two different alleles for a particular gene

Pedigrees
Pedigrees are used to analyze the pattern of inheritance of a particular trait
throughout a family. Pedigrees show the presence or absence of a trait as it
relates to the relationship among parents, offspring, and siblings.

Reading a pedigree
 Common pedigree symbols and identifiers
Common pedigree symbols.

Pedigrees represent family members and relationships using standardized

symbols.

By analyzing a pedigree, we can determine genotypes, identify phenotypes,

and predict how a trait will be passed on in the future. The information from
a pedigree makes it possible to determine how certain alleles are inherited:
whether they are dominant, recessive, autosomal, or sex-linked.

To start reading a pedigree:

1. Determine whether the trait is dominant or recessive. If the trait is

dominant, one of the parents must have the trait. Dominant traits will not skip
a generation. If the trait is recessive, neither parent is required to have the
trait since they can be heterozygous.
2. Determine if the chart shows an autosomal or sex-linked (usually X-
linked) trait. For example, in X-linked recessive traits, males are much more
commonly affected than females. In autosomal traits, both males and females
are equally likely to be affected (usually in equal proportions).
Example: Autosomal dominant trait

Pedigree showing the inheritance of freckles across three generations.

The diagram shows the inheritance of freckles in a family. The allele for
freckles (F) is dominant to the allele for no freckles (f).

At the top of the pedigree is a grandmother (individual I-2) who has freckles.
Two of her three children have the trait (individuals II-3 and II-5) and three
of her grandchildren have the trait (individuals III-3, III-4, and III-5).
[What is the genotype of individual I-2?]
Example: X-linked recessive trait

Pedigree showing the inheritance of colorblindness across four generations.

The diagram shows the inheritance of colorblindness in a family.

Colorblindness is a recessive and X-linked trait (\text{X}^{b})(Xb)left
parenthesis, start text, X, end text, start superscript, b, end superscript, right
parenthesis. The allele for normal vision is dominant and is represented by \
text{X}^{B}XBstart text, X, end text, start superscript, B, end superscript.

In generation I, neither parent has the trait, but one of their children (II-3) is
colorblind. Because there are unaffected parents that have affected offspring,
it can be assumed that the trait is recessive. In addition, the trait appears to
affect males more than females (in this case, exclusively males are affected),
suggesting that the trait may be X-linked.
 [What is the genotype of individual III-2?]

Common mistakes and misconceptions

 The presence of many affected individuals in a family does not always
mean that the trait is dominant. The terms dominant and recessive refer to
the way that a trait is expressed, not by how often it shows up in a family. In
fact, although it is uncommon, a trait may be recessive but still show up in all
generations of a pedigree.
 You may not always be able to determine the genotype of an individual
based on a pedigree. Sometimes an individual can either be homozygous
dominant or heterozygous for a trait. Often, we can use the relationships
between an individual and their parents, siblings, and offspring to determine
genotypes. However, not all carriers are always explicitly indicated in a
pedigree, and it may not be possible to determine based on the information
provided.

Intro to gene expression (central dogma)

How genes in DNA can provide instructions for proteins. The central dogma of molecular biology:
DNA → RNA → protein.

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Overview: Gene expression

DNA is the genetic material of all organisms on Earth. When DNA is
transmitted from parents to children, it can determine some of the children's
characteristics (such as their eye color or hair color). But how does the
sequence of a DNA molecule actually affect a human or other organism's
features? For example, how did the sequence of nucleotides (As, Ts, Cs, and
Gs) in the DNA of Mendel's pea plants determine the color of their flowers?

Genes specify functional products (such as

proteins)
A DNA molecule isn't just a long, boring string of nucleotides. Instead, it's
divided up into functional units called genes. Each gene provides instructions
for a functional product, that is, a molecule needed to perform a job in the
cell. In many cases, the functional product of a gene is a protein. For
example, Mendel's flower color gene provides instructions for a protein that
helps make colored molecules (pigments) in flower petals.

Diagram of how a gene can dictate a phenotype (observable feature) of an

organism. The flower color gene that Mendel studied consists of a stretch of
DNA found on a chromosome. The DNA has a particular sequence; part of it,
shown in this diagram, is 5'-GTAAATCG-3' (upper strand), paired with the
complementary sequence 3'-CATTTAGC-5' (lower strand). The DNA of the
gene specifies production of a protein that helps make pigments. When the
protein is present and functional, pigments are produced, and the flowers of a
plant have a purple color.
Image based on experimental data reported by Hellens et al.^11start superscript, 1, end superscript  and on
similar figure in Reece et al.^22squared.

The functional products of most known genes are proteins, or, more
accurately, polypeptides. Polypeptide is just another word for a chain of
amino acids. Although many proteins consist of a single polypeptide, some
 are made up of multiple polypeptides. Genes that specify polypeptides are
called protein-coding genes.

Not all genes specify polypeptides. Instead, some provide instructions to

build functional RNA molecules, such as the transfer RNAs and ribosomal
RNAs that play roles in translation. 
[More about protein-coding and RNA genes]

How does the DNA sequence of a gene specify a

particular protein?
Many genes provide instructions for building polypeptides. How, exactly,
does DNA direct the construction of a polypeptide? This process involves
two major steps: transcription and translation.

 In transcription, the DNA sequence of a gene is copied to make an RNA

molecule. This step is called transcription because it involves rewriting, or
transcribing, the DNA sequence in a similar RNA "alphabet." In eukaryotes,
the RNA molecule must undergo processing to become a mature messenger
RNA (mRNA).
 In translation, the sequence of the mRNA is decoded to specify the amino
acid sequence of a polypeptide. The name translation reflects that the
nucleotide sequence of the mRNA sequence must be translated into the
completely different "language" of amino acids.

Simplified schematic of central dogma, showing the sequences of the

molecules involved.

The two strands of DNA have the following sequences:

 5'-ATGATCTCGTAA-3' 3'-TACTAGAGCATT-5'

Transcription of one of the strands of DNA produces an mRNA that nearly

matches the other strand of DNA in sequence. However, due to a biochemical
difference between DNA and RNA, the Ts of DNA are replaced with Us in
the mRNA. The mRNA sequence is:

5'-AUGAUCUCGUAA-5'

Translation involves reading the mRNA nucleotides in groups of three; each

group specifies an amino acid (or provides a stop signal indicating that
translation is finished).

3'-AUG AUC UCG UAA-5'

AUG \rightarrow→right arrow Methionine AUC \rightarrow→right

arrow Isoleucine UCG \rightarrow→right arrow Serine UAA \
rightarrow→right arrow "Stop"

Polypeptide sequence: (N-terminus) Methionine-Isoleucine-Serine (C-

terminus)

Thus, during expression of a protein-coding gene, information flows from

DNA \rightarrow→right arrow RNA \rightarrow→right arrow protein. This
directional flow of information is known as the central dogma of molecular
biology. Non-protein-coding genes (genes that specify functional RNAs) are
still transcribed to produce an RNA, but this RNA is not translated into a
polypeptide. For either type of gene, the process of going from DNA to a
functional product is known as gene expression.
[Why are protein-coding genes expressed in two steps?]
Transcription
In transcription, one strand of the DNA that makes up a gene, called the non-
coding strand, acts as a template for the synthesis of a matching
(complementary) RNA strand by an enzyme called RNA polymerase. This
RNA strand is the primary transcript.

The two strands of DNA have the following sequences:

5'-ATGATCTCGTAA-3' 3'-TACTAGAGCATT-5'

The DNA opens up to form a bubble, and the lower strand serves as a
template for the synthesis of a complementary RNA strand. This strand is
called the template strand. Transcription of the template strand produces an
mRNA that nearly matches the other strand (coding strand) of DNA in
sequence. However, due to a biochemical difference between DNA and RNA,
the Ts of DNA are replaced with Us in the mRNA. The mRNA sequence is:

5'-AUGAUCUCGUAA-5'

The primary transcript carries the same sequence information as the non-
transcribed strand of DNA, sometimes called the coding strand. However,
the primary transcript and the coding strand of DNA are not identical, thanks
to some biochemical differences between DNA and RNA. One important
difference is that RNA molecules do not include the base thymine (T).
Instead, they have the similar base uracil (U). Like thymine, uracil pairs with
adenine.
[Other differences between DNA and RNA]
Transcription and RNA processing: Eukaryotes vs.
bacteria
In bacteria, the primary RNA transcript can directly serve as a messenger
RNA, or mRNA. Messenger RNAs get their name because they act as
messengers between DNA and ribosomes. Ribosomes are RNA-and-protein
structures in the cytosol where proteins are actually made.

In eukaryotes (such as humans), a primary transcript has to go through some

extra processing steps in order to become a mature mRNA.
During processing, caps are added to the ends of the RNA, and some pieces
of it may be carefully removed in a process called splicing. These steps do
not happen in bacteria.

Eukaryotic cell: Transcription takes place in the nucleus. The primary

transcript also undergoes processing steps in the nucleus in order to become a
mature mRNA. It is then exported to the cytosol, where it can associate with a
ribosome and direct synthesis of a polypeptide in the process of translation.

Bacterium: Transcription takes place in the cytosol. Because of this, the

mRNA doesn't have to travel anywhere before it can be translated by a
ribosome. In fact, a ribosome may begin translating a mRNA before it is even
fully transcribed (while transcription is still going on).

The location of transcription is also different between prokaryotes and

eukaryotes. Eukaryotic transcription takes place in the nucleus, where the
DNA is stored, while protein synthesis takes place in the cytosol. Because of
this, a eukaryotic mRNA must be exported from the nucleus before it can be
translated into a polypeptide. Prokaryotic cells, on the other hand, don't have
a nucleus, so they carry out both transcription and translation in the cytosol.

Translation
After transcription (and, in eukaryotes, after processing), an mRNA molecule
is ready to direct protein synthesis. The process of using information in an
mRNA to build a polypeptide is called translation.

The genetic code

During translation, the nucleotide sequence of an mRNA is translated into the
amino acid sequence of a polypeptide. Specifically, the nucleotides of the
mRNA are read in triplets (groups of three) called codons. There
are 616161 codons that specify amino acids. One codon is a "start" codon
that indicates where to start translation. The start codon specifies the amino
acid methionine, so most polypeptides begin with this amino acid. Three
other “stop” codons signal the end of a polypeptide.
These relationships between codons and amino acids are called the genetic
code. 
[Genetic code table]

The mRNA sequence is:

5'-AUGAUCUCGUAA-5'
Translation involves reading the mRNA nucleotides in groups of three; each
group specifies an amino acid (or provides a stop signal indicating that
translation is finished).

3'-AUG AUC UCG UAA-5'

AUG \rightarrow→right arrow Methionine AUC \rightarrow→right

arrow Isoleucine UCG \rightarrow→right arrow Serine UAA \
rightarrow→right arrow "Stop"

Polypeptide sequence: (N-terminus) Methionine-Isoleucine-Serine (C-

terminus)

Steps of translation
Translation takes place inside of structures known as ribosomes. Ribosomes
are molecular machines whose job is to build polypeptides. Once a ribosome
latches on to an mRNA and finds the "start" codon, it will travel rapidly
down the mRNA, one codon at a time. As it goes, it will gradually build a
chain of amino acids that exactly mirrors the sequence of codons in the
mRNA.

How does the ribosome "know" which amino acid to add for each codon? As
it turns out, this matching is not done by the ribosome itself. Instead, it
depends on a group of specialized RNA molecules called transfer
RNAS (tRNAs). Each tRNA has a three nucleotides sticking out at one end,
which can recognize (base-pair with) just one or a few particular codons. At
the other end, the tRNA carries an amino acid – specifically, the amino acid
that matches those codons.
 Translation occurring in a ribosome. The mRNA is bound to the ribosome,
where it can interact with tRNA molecule.

In this image, the mRNA has a sequence of:

3'-...AUG UAC AUC UCG GAU...-5'

A tRNA bound to the third codon (5'-AUC-3') has a complementary sequence

of 3'-UAG-5'. It bears a chain of polypeptides consisting of methionine and
isoleucine, which is attached to the tRNA by the isoleucine. To the right of
this tRNA, another tRNA is binding to the next codon (5'-UCG-3'). This
tRNA again has a complementary sequence of nucleotides (3'-AGC-5') and
bears the amino acid serine, which is the amino acid specified by the mRNA
codon. The serine carried by this tRNA will be added to the growing
polypeptide chain.

Other tRNAs carrying other amino acids are floating around in the
background. One carries Glu (glutamic acid) and has a sequence of
nucleotides at its end that reads 3'-CUU-5'. The other carries Asp (aspartic
acid) and has a sequence of nucleotides at its end that reads 3'-CUA-5'.

There are many tRNAs floating around in a cell, but only a tRNA that
matches (base-pairs with) the codon that's currently being read can bind and
deliver its amino acid cargo. Once a tRNA is snugly bound to its matching
codon in the ribosome, its amino acid will be added to the end of the
polypeptide chain.

1. Matching tRNA binds to exposed codon in rightmost slot of ribosome.

2. Chain of amino acids is transferred from tRNA in middle slot of ribosome
onto the amino acid of the tRNA in the rightmost slot. This has the effect of
adding the amino acid to the end of the amino acid chain.
 3. The ribosome shifts one codon over. The tRNA formerly in the middle slot
moves to the leftmost slot and exits the ribosome. The tRNA formerly in the
right slot moves into the middle slot and continues to hold the amino acid
chain. A new codon is exposed in the rightmost slot for a new tRNA to bind
to.
This process repeats many times, with the ribosome moving down the mRNA
one codon at a time. A chain of amino acids is built up one by one, with an
amino acid sequence that matches the sequence of codons found in the
mRNA. Translation ends when the ribosome reaches a stop codon and
releases the polypeptide.

What happens next?

Once the polypeptide is finished, it may be processed or modified, combine
with other polypeptides, or be shipped to a specific destination inside or
outside the cell. Ultimately, it will perform a specific job needed by the cell
or organism – perhaps as a signaling molecule, structural element, or
enzyme!

Summary:
 DNA is divided up into functional units called genes, which may specify
polypeptides (proteins and protein subunits) or functional RNAs (such as
tRNAs and rRNAs).
 Information from a gene is used to build a functional product in a process
called gene expression.
 A gene that encodes a polypeptide is expressed in two steps. In this process,
information flows from DNA \rightarrow→right arrow RNA \
 rightarrow→right arrow protein, a directional relationship known as
the central dogma of molecular biology.
 Transcription: One strand of the gene's DNA is copied into RNA. In
eukaryotes, the RNA transcript must undergo additional processing steps in
order to become a mature messenger RNA (mRNA).
 Translation: The nucleotide sequence of the mRNA is decoded to specify
the amino acid sequence of a polypeptide. This process occurs inside a
ribosome and requires adapter molecules called tRNAs.
 During translation, the nucleotides of the mRNA are read in groups of three
called codons. Each codon specifies a particular amino acid or a stop signal.
This set of relationships is known as the genetic code.

Explore outside of Khan Academy

Do you want to learn more about transcription? Check out this scrollable
interactive from LabXchange.

Do you want to learn more about translation? Check out this scrollable

interactive from LabXchange.

LabXchange is a free online science education platform created at Harvard’s

Faculty of Arts and Sciences and supported by the Amgen Foundation.
[References]

Introduction
Take a moment to look at your hands. The bone, skin, and muscle you see are
made up of cells. And each of those cells contains many millions of
proteins^11start superscript, 1, end superscript. As a matter of fact, proteins
are key molecular "building blocks" for every organism on Earth!
 How are these proteins made in a cell? For starters, the instructions for
making proteins are "written" in a cell’s DNA in the form of genes. If that
idea is new to you, you may want to check out the section on DNA to RNA
to protein (central dogma) before getting into the nitty-gritty of building
proteins.

Basically, a gene is used to build a protein in a two-step process:

 Step 1: transcription! Here, the DNA sequence of a gene is "rewritten" in

the form of RNA. In eukaryotes like you and me, the RNA is processed (and
often has a few bits snipped out of it) to make the final product, called a
messenger RNA or mRNA.
 Step 2: translation! In this stage, the mRNA is "decoded" to build a protein
(or a chunk/subunit of a protein) that contains a specific series of amino
acids. 
[What exactly is an "amino acid"?]

The central dogma of molecular biology states that information flows from
DNA (genes) to mRNA through the process of transcription, and then to
proteins through the process of translation.
_Image modified from "Central dogma of molecular biochemistry with enzymes," by Daniel Horspool (CC
BY-SA 3.0). The modified image is licensed under a CC BY-SA 3.0 license._

In this article, we'll zoom in on translation, getting an overview of the process

and the molecules that carry it out.
The genetic code
During translation, a cell “reads” the information in a messenger RNA
(mRNA) and uses it to build a protein. Actually, to be a little more techical,
an mRNA doesn’t always encode—provide instructions for—a whole
protein. Instead, what we can confidently say is that it always encodes
a polypeptide, or chain of amino acids.
[Wait, what is the difference?]

Genetic code table. Each three-letter sequence of mRNA nucleotides

corresponds to a specific amino acid, or to a stop codon. UGA, UAA, and
UAG are stop codons. AUG is the codon for methionine, and is also the start
codon.
_Image credit: "The genetic code," by OpenStax College, Biology (CC BY 3.0)._

In an mRNA, the instructions for building a polypeptide are RNA nucleotides

(As, Us, Cs, and Gs) read in groups of three. These groups of three are
called codons.

There are 616161 codons for amino acids, and each of them is "read" to

specify a certain amino acid out of the 202020 commonly found in proteins.
One codon, AUG, specifies the amino acid methionine and also acts as
a start codon to signal the start of protein construction.

There are three more codons that do not specify amino acids. These stop
codons, UAA, UAG, and UGA, tell the cell when a polypeptide is complete.
All together, this collection of codon-amino acid relationships is called
the genetic code, because it lets cells “decode” an mRNA into a chain of
amino acids.

Each mRNA contains a series of codons (nucleotide triplets) that each

specifies an amino acid. The correspondence between mRNA codons and
amino acids is called the genetic code.

5' AUG - Methionine ACG - Threonine GAG - Glutamate CUU - Leucine

CGG - Arginine AGC - Serine UAG - Stop 3'
Image modified from "RNA-codons-aminoacids," by Thomas Splettstoesser (CC BY-SA 4.0). The modified
image is licensed under a  CC BY-SA 4.0 license.
Overview of translation
How is an mRNA "read" to make a polypeptide? Two types of molecules
with key roles in translation are tRNAs and ribosomes.

Transfer RNAs (tRNAs)

Transfer RNAs, or tRNAs, are molecular "bridges" that connect mRNA
codons to the amino acids they encode. One end of each tRNA has a
sequence of three nucleotides called an anticodon, which can bind to specific
mRNA codons. The other end of the tRNA carries the amino acid specified
by the codons.

There are many different types of tRNAs. Each type reads one or a few
codons and brings the right amino acid matching those codons.

Ribosomes are composed of a small and large subunit and have three sites
where tRNAs can bind to an mRNA (the A, P, and E sites). Each tRNA
vcarries a specific amino acid and binds to an mRNA codon that is
complementary to its anticodon.
Image modified from "Translation: Figure 3," by OpenStax College, Biology (CC BY 4.0).
Ribosomes
Ribosomes are the structures where polypeptides (proteins) are built. They
are made up of protein and RNA (ribosomal RNA, or rRNA). Each
ribosome has two subunits, a large one and a small one, which come together
around an mRNA—kind of like the two halves of a hamburger bun coming
together around the patty.

The ribosome provides a set of handy slots where tRNAs can find their
matching codons on the mRNA template and deliver their amino acids. These
slots are called the A, P, and E sites. Not only that, but the ribosome also acts
as an enzyme, catalyzing the chemical reaction that links amino acids
together to make a chain.

Want to learn more about the structure and function of tRNAs and
ribosomes? Check out the tRNA and ribosomes article!

Steps of translation
Your cells are making new proteins every second of the day. And each of
those proteins must contain the right set of amino acids, linked together in
just the right order. That may sound like a challenging task, but luckily, your
cells (along with those of other animals, plants, and bacteria) are up to the
job.

To see how cells make proteins, let's divide translation into three stages:
initiation (starting off), elongation (adding on to the protein chain), and
termination (finishing up).
 Getting started: Initiation
In initiation, the ribosome assembles around the mRNA to be read and the
first tRNA (carrying the amino acid methionine, which matches the start
codon, AUG). This setup, called the initiation complex, is needed in order for
translation to get started.

Extending the chain: Elongation

Elongation is the stage where the amino acid chain gets longer. In
elongation, the mRNA is read one codon at a time, and the amino acid
matching each codon is added to a growing protein chain.

Each time a new codon is exposed:

 A matching tRNA binds to the codon

 The existing amino acid chain (polypeptide) is linked onto the amino acid of
the tRNA via a chemical reaction
 The mRNA is shifted one codon over in the ribosome, exposing a new codon
for reading
 Elongation has three stages:

1) The anticodon of an incoming tRNA pairs with the mRNA codon exposed
in the A site.

2) A peptide bond is formed between the new amino acid (in the A site) and
the previously-added amino acid (in the P site), transferring the polypeptide
from the P site to the A site.

3) The ribosome moves one codon down on the mRNA. The tRNA in the A
site (carrying the polypeptide) shifts to the P site. The tRNA in the P site
shifts to the E site and exits the ribosome.
Image based on similar diagram in Reece et al.^22squared

During elongation, tRNAs move through the A, P, and E sites of the

ribosome, as shown above. This process repeats many times as new codons
are read and new amino acids are added to the chain.

For more details on the steps of elongation, see the stages of

translation article.

Finishing up: Termination

Termination is the stage in which the finished polypeptide chain is released.
It begins when a stop codon (UAG, UAA, or UGA) enters the ribosome,
triggering a series of events that separate the chain from its tRNA and allow
it to drift out of the ribosome.

After termination, the polypeptide may still need to fold into the right 3D
shape, undergo processing (such as the removal of amino acids), get shipped
to the right place in the cell, or combine with other polypeptides before it can
do its job as a functional protein.
 ntroduction
Have you ever written a secret message to one of your friends? If so, you
may have used a code to keep the message hidden. For instance, you may
have replaced the letters of the word with numbers or symbols, following a
particular set of rules. In order for your friend to understand the message,
they would need to know the code and apply the same set of rules, in reverse,
to decode it.

Decoding messages is also a key step in gene expression, in which

information from a gene is read out to build a protein. In this article, we'll
take a closer look at the genetic code, which allows DNA and RNA
sequences to be "decoded" into the amino acids of a protein.

Background: Making a protein

Genes that provide instructions for proteins are expressed in a two-step
process.

 In transcription, the DNA sequence of a gene is "rewritten" in RNA. In

eukaryotes, the RNA must go through additional processing steps to become
a messenger RNA, or mRNA.
 In translation, the sequence of nucleotides in the mRNA is "translated" into
a sequence of amino acids in a polypeptide (protein chain).
If this is a new concept for you, you may want to learn more by watching
Sal's video on transcription and translation.
 Codons
Cells decode mRNAs by reading their nucleotides in groups of three,
called codons. Here are some features of codons:

 Most codons specify an amino acid

 Three "stop" codons mark the end of a protein
 One "start" codon, AUG, marks the beginning of a protein and also encodes
the amino acid methionine
Codons in an mRNA are read during translation, beginning with a start codon
and continuing until a stop codon is reached. mRNA codons are read from 5'
to 3' , and they specify the order of amino acids in a protein from N-terminus
(methionine) to C-terminus.

The mRNA sequence is:

5'-AUGAUCUCGUAA-5'

Translation involves reading the mRNA nucleotides in groups of three; each

group specifies an amino acid (or provides a stop signal indicating that
translation is finished).
 3'-AUG AUC UCG UAA-5'

AUG \rightarrow→right arrow Methionine (Start) AUC \rightarrow→right

arrow Isoleucine UCG \rightarrow→right arrow Serine UAA \
rightarrow→right arrow "Stop"

Polypeptide sequence: (N-terminus) Methionine-Isoleucine-Serine (C-

terminus)
[What do 5' and 3' mean?]

[What are the N- and C-terminus?]

The genetic code table

The full set of relationships between codons and amino acids (or stop signals)
is called the genetic code. The genetic code is often summarized in a table. 
[How do you read the codon table?]
 Genetic code table. Each three-letter sequence of mRNA nucleotides
corresponds to a specific amino acid, or to a stop codon. UGA, UAA, and
UAG are stop codons. AUG is the codon for methionine, and is also the start
codon.
Image credit: "The genetic code," by OpenStax College, Biology (CC BY 3.0).

Notice that many amino acids are represented in the table by more than one
codon. For instance, there are six different ways to "write" leucine in the
language of mRNA (see if you can find all six).

An important point about the genetic code is that it's universal. That is, with
minor exceptions, virtually all species (from bacteria to you!) use the genetic
code shown above for protein synthesis.
Reading frame
To reliably get from an mRNA to a protein, we need one more concept: that
of reading frame. Reading frame determines how the mRNA sequence is
divided up into codons during translation.

That's a pretty abstract concept, so let's look at an example to understand it

better. The mRNA below can encode three totally different proteins,
depending on the frame in which it's read:
 mRNA sequence: 5'-UCAUGAUCUCGUAAGA-3'

Read in Frame 1:

5'-UCA UGA UCU CGU AAG A-3'

Ser-STOP-Ser-Arg-Lys

Read in Frame 2:

5'-U CAU GAU CUC GUA AGA-3'

His-Asp-Leu-Val-Arg

Read in Frame 3:

5'-UC AUG AUC UCG UAA GA-3'

Met(Start)-Ile-Ser-STOP

The start codon's position ensures that Frame 3 is chosen for translation of the
mRNA.

So, how does a cell know which of these protein to make? The start codon is
the key signal. Because translation begins at the start codon and continues in
successive groups of three, the position of the start codon ensures that the
mRNA is read in the correct frame (in the example above, in Frame 3).

Mutations (changes in DNA) that insert or delete one or two nucleotides can
change the reading frame, causing an incorrect protein to be produced
"downstream" of the mutation site:
Illustration shows a frameshift mutation in which the reading frame is altered
by the deletion of two amino acids.
_Image credit; "The genetic code: Figure 3," by OpenStax College, Biology, CC BY 4.0._

How was the genetic code discovered?

The story of how the genetic code was discovered is a pretty cool and epic
one. We've stashed our version in the pop-up below, so as not to distract you
if you're in a hurry. However, if you have some time, it's definitely interesting
reading. 
[Discovery of the genetic code]

I always like to imagine how cool it would have been to be one of the people
who discovered the basic molecular code of life. Although we now know the
code, there are many other biological mysteries still waiting to be solved
(perhaps by you!).
[Attribution and references]