HUMAN REPRODUCTIONBIOLOGY 269

Humans:

Reproduce sexually with internal fertilization

All cells in adult except gametes contain 46 chromosomes;

sperm (small, many) and eggs (large, one or two) contain

23 chromosomes.

Fertilization combines sperm and egg. Resulting cell, called

a zygote, contains 46 chromosomes. All cells formed from

the zygote also contain 46 chromosomes.

Human Life Stages:

Preembryo - Undifferentiated cell division

Embryo - Formation of specific tissues & organs

Fetus - Maturation of organs & systems

Neonate - Adjustment to life outside uterus

Infant - Rapid growth, particularly nervous

Child - Continued growth

Pubescent - Sexual traits & fertility occur

Adolescent - Sexual & psychological maturation

Adult - Slow or no growth; reproductive years

Senescence - Degeneration of tissues/organs/systems

It all begins when one egg (oocyte) is fertilized by one sperm.

This occurs a few hours after both:

a. The egg is released from

the ovary

b. The sperm are deposited

in the vagina during

sexual intercourse

It occurs within the Fallopian tube, about one third of the way from the ovary to the uterus

The basis of genetic inheritance:

Each chromosome consists of a very long molecule called deoxyribonucleic acid, or DNA.

The basis of genetic inheritance:

Genes are short segments of this DNA, lined up one after the other

The purpose of fertilization:

To combine into one cell, the zygote:

Half of the father’s genetic material (genes and chromosomes)

and

Half of the mother’s genetic material (genes and chromosomes)

This requires that, before fertilization:

- The father places only half of his chromosomes into each sperm

- The mother places only half of her chromosomes into each egg

and

This is not random: specific chromosomes need to end up in each sperm and egg

Except for your eggs or your sperm, each of your cells contains 46 chromosomes, arranged in 23 pairs

- Half of these chromosomes (one of each pair) came from your father

- Half of these chromosomes (one of each pair) came from your mother

22 of these pairs = same in both sexes, called autosomes

I pair = sex chromosomes: Two X chromosomes = female One X + one Y chromosome = male

Red = from mother; Green = from father

Each of your eggs or sperm contains 23 chromosomes soDuring their formation they keep only half of the original 46

chromosomes

More specifically: Each sperm or egg carries one (and only one!) chromosome of each pair

This is a mixture of chromosomes you got from your mothermother and chromosomes you got from your fatherfather

This reduction in the number of chromosomes, from 46 to 23 in sperm or eggs, requires a specific type of cell division called meiosis

This is different than the type of cell division, called mitosis, in which cells simply make genetically identical copies of themselves

Key features:

Mitosis: One cell copies its chromosomes and then divides in such a way that each of the two new cells is genetically identical to the original: each contains all 23 pairs = 46 chromosomes

Meiosis: One cell copies its chromosomes and then divides twice in succession so that four new cells are formed, each of which contains 23 single chromosomes (no pairs)

You’re in luck! For this course, you don’t need to know any more detail than that about mitosis vs meiosis:

Mitosis: two identical cells with 46 chromosomes each

Meiosis: four genetically different cells, 23 chromosomes each

While both sperm and eggs are formed by meiosis, the processes are not identical:

Spermatogenesis forms 4 small, equally sized sperm. Very rapid - hundreds of millions of sperm produced each day.

Oogenesis forms one very large cell and three small cells called polar bodies, which die.Much slower - one or two eggs (oocytes) produced each month.

Recall:

Fertilization combines sperm (23 chromosomes) and egg (23 chromosomes) to form a zygote (46 chromosomes). This zygote divides repeatedly by mitosis to form the billions of cells which make up the different organs of the body, each of which contains these same 46 chromosomes.

Also recall:

Your chromosomes are arranged in pairs (one from each parent),

so you have two genes for each “trait”:

For example You received a gene for hair color from you mother You received a gene for hair color from your father

You received a gene for blood type from your mother You received a gene for blood type from your father

You received a gene from your mother for whether or not your earlobes are attached You received a gene from your father for whether or not your earlobes are attached

Not all genes are for visible characterisitics

in fact the vast majority are not.

Your genes are also responsible for everything your cells produce:

(enzymes, hormones, antibodies, clotting factors, blood proteins,

extracellular proteins, etc.)

and everything they do:

(cell division, cell growth, chemical reactions, forming membranes,

cellular transport, electrical signals, contraction, metabolism,

cell death, etc.)

Two genes for the same trait, carried on different chromosomes of a pair (one from your father, one from your mother), are called alleles

These alleles may be the same (e.g. both are for brown hair)

or different (one for brown hair, one for blond hair)

You are considered homozygous for a trait if both alleles are the same, or heterozygous if the two alleles are different

While all cells (except sperm and eggs) CONTAIN all of the chromosomes and thus all of the genes

Not all of the cells EXPRESS all of their genes

That is: only some of the genes will be expressed in any particular cell. e.g. skin, hair, and eye cells express genes for color, but liver cells or heart cells do not; cells in your pancreas express the genes to produced insulin, other types of cells do not.

Sometimes one allele will always Dominant

be expressed if it is present

Sometimes an allele will be expressed Recessive

only if a dominant allele not present

Sometimes the two different alleles Codominant

will both be completely expressed

Sometimes one allele will only be Incompletely

partially expressed if a recessive dominant

allele is also present

What alleles you carry (regardless of which ones are actually expressed) is your genotype

What traits you actually express (regardless of which alleles are actually present) is your phenotype

Example:

Allele (gene) for hairy ears is dominant “H”

Allele (gene) for hairless ears is recessive “h”

(remember: you have two alleles for this trait: one from your mother and one from your father)

If genotype is HH (homozygous), phenotype is hairy ears

If genotype is Hh (heterozygous), phenotype is hairy ears

If genotype is hh (homozygous), phenotype is hairless ears

Example:

Allele (gene) for type A blood is dominant “A”

Allele (gene) for type B blood also dominant “B”

Allele (gene) for type O blood is recessive “o”

(remember: you have only two alleles for this trait: one from your mother and one from your father)

If genotype is AA (homozygous), phenotype is type A blood

If genotype is Ao (heterozygous), phenotype is type A blood

If genotype is BB (homozygous), phenotype is type B blood

If genotype is Bo (heterozygous), phenotype is type B blood

If genotype is AB (heterozygous), phenotype is type AB blood

If genotype is oo (homozygous), phenotype is type O blood

Example:

Allele (gene) for producing hormone insulin is dominant “I”

Allele (gene) for not producing insulin is recessive “i”

(remember: you have two alleles for this trait: one from your mother and one from your father)

If genotype is II (homozygous), phenotype is producing insulin

If genotype is Ii (heterozygous), phenotype is producing insulin

If genotype is ii (homozygous), phenotype is no insulin produced

A handy tool for doing this is a Punnett square, in which each allele in the sperm or egg is listed, along with all possible combinations upon fertilization

Allele Allele

CombinedAlleles

If you know the genotypes of both parents, you can calculate the probability of a child having a particular genotype and/or a particular phenotype.

Allele

Allele

CombinedAlleles

CombinedAlleles

CombinedAlleles

Allele (gene) for hairy ears is dominant “H”Allele (gene) for hairless ears is recessive “h”

Suppose a homozygous recessive man and a heterozygous woman have children. What are the probabilities of the resulting genotypes and phenotypes?

Example:

H h

h

h

Hh hh

Hh hh

Allele (gene) for hairy ears is dominant “H”Allele (gene) for hairless ears is recessive “h”

Suppose both parents are heterozygous. What are the probabilities of the resulting genotypes and phenotypes?

Change things a bit:

H h

H

h

HH Hh

Hh hh

Alleles (genes) for type A & type B blood are codominant “A”, “B”Allele (gene) for type O blood is recessive to both A and B “o”

Suppose the father is homozygous for type A blood and the mother is heterozygous for type B blood. What are the probabilities of the resulting genotypes and phenotypes?

Example:

B o

A

A

AB Ao

AB Ao

Alleles (genes) for type A & type B blood are codominant “A”, “B”Allele (gene) for type O blood is recessive to both A and B “o”

Suppose the father is heterozygous for type A blood and the mother is heterozygous for type B blood. What are the probabilities of the resulting genotypes and phenotypes?

Change the parents’ blood types:

B o

A

o

AB Ao

Bo oo

Alleles (genes) for type A & type B blood are codominant “A”, “B”Allele (gene) for type O blood is recessive to both A and B “o”

Could a father who has type A blood (you don’t know if he is homozygous or heterozygous) and a mother who has type AB blood have a child with type O blood?

Let’s try it from a different perspective:

A B

A

?

AA AB

A? B?

Allele (gene) for brown eyes is dominant to other colors “B”Allele (gene) for green eyes is dominant over blue “g”Allele (gene) for blue eyes is recessive to all other colors “b”

Suppose the father is heterozygous with alleles for brown eyes and for green eyes, and the mother is heterozygous with alleles for green eyes and blue eyes. What are the probabilities of the resulting genotypes and phenotypes?

Here’s another one:

g b

B

g

Bg Bb

gg bg

The allele (gene) for straight hair “S” is incompletely dominant over the allele for curly hair “s”; the heterozygous genotype produces an intermediate form, wavy hair.

Suppose the father is heterozygous, and the mother is homozygous for curly hair. What are the probabilities of the resulting genotypes and phenotypes?

Example:

s s

S

s

Ss Ss

ss ss

The allele (gene) for straight hair “S” is incompletely dominant over the allele for curly hair “s”; the heterozygous genotype produces an intermediate form, wavy hair.

Suppose the both parents are heterozygous. What are the probabilities of the resulting genotypes and phenotypes?

Let’s change the parents genetics:

S s

S

s

SS Ss

Ss ss

Disclaimer:Genetics is not really as simple as I have presented:

Many traits are controlled by more than one pair of alleles, with many different genes determining the final phenotype (e.g. skin color varies from very light to very dark, depending on how many pairs of alleles contain one for producing the pigment melanin)

Many alleles considered “dominant” are really incompletely dominant, with the recessive allele being only slightly expressed (e.g. individuals who are homozygous for brown eyes have darker brown eyes than individuals who are heterozygous)

Disclaimer:Genetics is not really as simple as I have presented:

This can vary among different cells in the same tissue (e.g. many individuals have regions of different colors in the same eye)

The expression of an otherwise dominant allele can be blocked by a different pair of alleles (e.g. an individual with an allele for brown eyes may not express it if another gene turns off its expression, thus having green or blue eyes).

Many genes (alleles) produce physical / physiological abnormalities or disease

All of the genetic “rules” just discussed can apply to these as well:

- Dominance and recessiveness

- Codominance and incomplete dominance

- Multiple pairs of alleles

- Blockage

- Different expression in different cells

The allele which produces the disease neurofibromatosis (“N”) is dominant to the normal allele (“n”)

What is the probability of a child getting this disease if one parent is normal but the other carries an allele for the disease?

Example:

N n

n

n

Nn nn

Nn nn

Neurofibromatosis: Autosomal dominant

The allele which produces the disease neurofibromatosis (“N”) is dominant to the normal allele (“n”)

What if both parents are heterozygous for the disease-producing allele?

Change the parents’ genetics:

N n

N

n

NN Nn

Nn nn

The allele which produces the disease achondroplasia (“a”) is recessive to the normal allele (“A”)

What is the probability of a child getting this disease if one parent is normal but the other carries one allele for the disease?

Example:

A A

A

a

AA AA

Aa Aa

The allele which produces the disease achondroplasia (“a”) is recessive to the normal allele (“A”)

What if both parents are heterozygous for the disease-producing allele?

Change the parents’ genetics:

A a

A

a

AA Aa

Aa aa

“Special case” when an allele is located on the X-chromosome

Men (genotype = XY) will have only one allele for that trait since they have only one X-chromosome, and that allele will always be expressed (the Y chromosome carries completely different alleles than the X chromosome)

Women (genotype = XX) will have two alleles for that trait, just as we have been discussing

If that allele is disease-producing, a man will always express the disease regardless of whether it is dominant or recessive to the “normal” allele

Duchenne muscular dystrophy is produced by an X-linked recessive allele “Xd”

Suppose the father is normal (XDY) but the mother is heterozygous for the disease (XD Xd)

Example:

XD Xd

XD

Y

XD XD XD Xd

XDY XdY

Chromosomes are formed by long strands of a molecule called deoxyribonucleic acid, or DNA. This molecule can best be thought of by analogy to the written English language, in which letters make

up words, which make up sentences, which make up paragraphs.

In DNA:

There are four possible letters, which we will call A, C, G, and T;

All words are exactly three letters long;

Sentences are typically thousands of words long.

Each sentence would be one gene;

The entire paragraph would be one chromosome

Let’s rephrase that:

Chromosomes are formed by very long molecules called DNA, which consist of genes lined up one-after-the-other.

Each of these genes consists of many three-letter groupings of A, C, G, and T, lined up one-after-the-other

For example, a very short gene might consist of

A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C-G-T-C

Things often go wrong during mitosis or meiosis:

Minor changes, or mutations, may occur in a gene

1) A piece of it may be deleted, for example

If A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C

becomes A-C-T-G-A-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C (three letters deleted)

Or A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C

becomes A-C-T-G-A-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C (one letter deleted)

(Minor changes, or mutations, may occur in a gene)

2) A piece of it may be added, for example

If A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A

becomes A-C-T-G-A-C-T-G-C-G-A-C-T-G-C T-T-A-A-C-C-T-C-A (. . six letters added. .)

3) One or more of the “letters” may substituted, for example

If A-C-T-G-A-C-T-G-C-T-T-A-A-C-C-T-C-A-G-A-C-C-C-C becomes A-C-T-G-T-C-T-G-C-T-G-A-A-C-C-C-C-A-G-A-C-C-C-T

While seemingly minor at the letter level, mutations will in fact have very serious effects on the ability of that gene to produce its normal trait, just as it would in the English language: For example

If: The cat and the dog and the pig ate ham all day

became The caa ndt hed oga ndt hep iga teh ama lld ay (deletion)

If: The cat and the dog and the pig ate ham all day

became The bat and the fog and toe pig ate hat all may

(substitutions)

Just as with the language examples given, the vast majority of mutations cause the gene to become “nonsense”: the trait is no longer produced.

Many cases: expression of the trait is necessary for life, so mutation kills whatever cell it occurs in.

Far fewer cases: Cell will still be able to survive, but will be missing something – for example, if the cell normally produced the brown pigment melanin and this gene mutates, the cell could still be alive but will no longer be brown.

Extremely few circumstances (once out of many millions of mutations): absence of a trait improves the function of the cell – for example, if it could now produce even more energy than it did before.

Another genetic change which occurs during mitosis or meiosis is

nondisjunction, in which normal chromosomes may get distributed abnormally into the daughter cells

As with mutations, the vast majority of cells in which nondisjunction occurs will die, but a few may live and develop abnormal functions.

If a cell dies during mitosis or meiosis, it usually has very little effect on the organ which contains that cell, since it can easily be replaced by mitosis of another, healthy cell.

However, if a genetically abnormal cell survives from mitosis, it can have a serious effect because of its abnormal function:

• It may produce something which is toxic to other cells;

• It may produce things which make other cells function abnormally;

• It may lose its ability to regulate its growth and division = Cancer;

If a genetically abnormal cell (sperm or egg) survives meiosis and is then involved in fertilization, the changes can be passed on to the children

In most cases, genetically abnormal embryos die before birth.

In a few cases, however, they survive.

In fact the vast majority of birth defects are caused by genetic abnormalities.

Down syndrome: Trisomy 21

One of the more common birth defects involves nondisjunction of the X and Y sex chromosomes

Recall: Each egg normally carries one X chromosome and no Y

Each sperm normally carries either one X chromosome or

one Y chromosome

Therefore, cells in a normal zygote and embryo will have either two X chromosomes or one X and one Y chromosome

X X

X

Y

XX XX

XY XY

As a result of nondisjunction, a sperm or egg may either - Be missing the sex chromosome, or - Have an extra sex chromosome

If this sperm or egg is involved in fertilization, the zygote and all subsequent cells will either

- Be missing one sex chromosome, or

- Have an extra sex chromosome

Turner’s Syndrome results from a genotype of only 45 chromosomes instead of the usual 46, with only one X sex chromosome (“XO” or “X-”).

This occurs when either:

- An abnormal egg with no X chromosome is fertilized by a normal sperm carrying an X chromosome or

- A normal egg with one X chromosome is fertilized by an abnormal sperm carrying neither X or Y chromosome

Short female; poorly developed secondary sexual characteristics; Never enters puberty and therefore sterile.Usually other physical defects in heart, lungs, vessels, bonesOccasionally mentally retarded

Turner’s Syndrome

X0

Kleinfelter’s Syndrome results from a genotype of 47 chromosomes instead of the usual 46, with two X chromosomes and a Y (“XXY”).

This occurs when either:

- An abnormal egg with two X chromosomes is fertilized by a normal sperm carrying a Y chromosome or

- A normal egg with one X chromosome is fertilized by an abnormal sperm carrying both X and Y chromosomes

Tall male with long, skinny fingers and toes; Poorly developed secondary sexual characteristics; SterileOften displays increased aggression Often, but not always, slight mental retardation

Kleinfelters Syndrome: XXY

Metafemale Syndrome results from a genotype of 47 chromosomes instead of the usual 46, with three X chromosomes (“XXX”).

This occurs when an abnormal egg with two X chromosomes is fertilized by a normal sperm carrying an X chromosome

Normal-appearing female; Abnormalities in ovulation and menstruation; Decreased fertility, although usually not sterileNo mental retardation

XYY Syndrome, as you might expect, results from a genotype of 47 chromosomes, with one X and two Y chromosomes (“XYY”).

This occurs when a normal egg with one X chromosome is fertilized by an abnormal sperm carrying two Y chromosomes

Normal-appearing male, usually taller than usual; Prone to infections and inflammations, particularly acne; Decreased fertility, although usually not sterileNo mental retardation

The End

X