Cell Biology Chapter 19 Sexual Reproduction and Genetics

What is aneuploidy?

Abnormal number of chromosomes. The freq. of chromosome mis-segregration during the production of human gametes is remarkably high, particularly in females: nondisjunction occurs in about 10% of the meiosis in human oocytes, giving rise to eggs that contain the wrong number of chromosomes a condition called aneuploidy.

The major of polymorphisms are due to what?

Substitution of a single nucleotide sequence called single-nucleotide polymorphisms or SNPs. The rest are due largely to insertions or deletions called indels when the change is small, or copy number variants (CNVs) when it is large.

Why are gain-of-function genes normally dominant?

Such mutations are normally dominate, for example, certain mutations in the Ras gene generate a form of the protein that is always active. Because normal Ras protein is involved in controlling cell proliferation, the mutant protein drives cells to multiply inappropriately, even in the absence of signals that are normally required to stimulate cell division. This promotes cancers. About 30% of all human cancers contain such dominant, gain-of-function mutations in the Ras gene.

Define polymorphisms.

The DNA sequence for where there are two or more variants are present at high frequencies in the general population.

Where does meiosis begin?

Meiosis begins in specialized germ-line cells that reside in the ovaries or testes. Like somatic cell, these germ-line cells are diploid.

What dictates the appearance of the organism?

The appearance or phenotype of the organism depends on which versions of each allele it inherits. Mendel supposed that for any pair of alleles, one allele is dominant and the other is recessive, or hidden.

Compare and contrast asexually and sexual reproduction.

1. Asexual reproduction is a mode of reproduction in which an organism arises from a single parent, producing an individual genetically identical to the parent. Includes budding, binary fission, and parthenogenesis. 2. Sexual reproduction is a mode of reproduction in which the genomes of two individuals are mixed to produce an individual that is genetically distinct from its parents.

Describe the characteristics of organisms that generally divide via sexual reproduction.

1. Diploid or their cells contain two sets of chromosomes, one inherited from each parent. 2. Maternal and Paternal chromosome sets are very similar. 3. Sex chromosomes distinguish males from females.

Compare and contrast mitosis and meiosis DNA replication.

1. In mitosis it duplicates all of its chromosomes. This duplication allows a full set of chromosomes, including a maternal and paternal set, to be transmitted to each daughter cell. 2. Meiosis halves this diploid chromosome complement producing haploid gametes that carry only one set of chromosomes, it too begins with a round of chromosome duplication. The subsequent reduction in chromosome number occurs because this single round of duplication is followed by two successive rounds of nuclear division without further DNA replication.

Before a eukaryotic cell divides by either meiosis or mitosis it first must duplicate its chromosomes resulting in sister chromatids. Describe the difference in how these sister chromatids are then handled by meiosis vs mitosis.

1. In mitosis, the duplicated chromosomes line, single file, at the metaphase plate. They are then segregated into two daughter nuclei by the mitotic spindle. 2. In meiosis, the need to halve the number of chromosomes introduced an extra demand on the cell-division machinery. The germ-line cell must keep track of the maternal and paternal homologs to ensure that each of the four haploid cells produced by meiosis will receive a sister chromatid from each chromosome set. Meiosis beings with a complex and time-consuming process called pairing, in which each duplicated homolog are brought together during a stage called meiotic prophase (or prophase I). It is these pairs of duplicated homologs that line up at the metaphase plate in meiosis I.

Explain the basic steps of meiosis?

1. In the first step of meiosis, all of these chromosomes are duplicated, and the resulting copies remain closely attached to each other, as they would during ordinary mitosis. 2. In next phase of the process is unique to meiosis. During this phase, called metotic prophase, each duplicated paternal chromosome locates and then attaches itself along its entire length to the corresponding duplicated maternal homolog. This process is called pairing, and is of fundamental importance to meiosis, as it allows the segregation of homologous chromosome pairs during the first meiotic division (meiosis II). 3. The two duplicated chromosomes within each homolog are then separated during the second meiotic division (meiosis II), producing four haploid nuclei. Because chromosome segregation during meiosis I and II are random, each haploid gamete will receive a different mixture of maternal and paternal chromosomes. Thus, meiosis produces four nuclei that are genetically dissimilar and that contain exactly half as many chromosomes as the original parent germ-line cells.

How does sex chromosomes get divided in sexual reproduction in humans?

1. Y chromosome carries genes that specify the developments of a male. 2. X chromosomes carries genes that specify the developments of a female. 3. Males inherit a Y chromosome from their father and an X chromosome from their mother. 4.Females inherit one X chromosome from each parent.

What is a genetic screen?

A genetic screen typically involves examining many thousand of mutagenized individuals to find the few that show a specific altered phenotype of interest.

Can loss-of-function mutations be dominant too?

A mutation that causes a protein to misfolded in a loss-of-function mutation in a heterozygote, 50% of the proteins produced would be misfolded and inactive, while the other 50% would be active. However, the misfolded protein could go on the form aggregates that can cause severe problems for the cell creating prions. Because of the widespread impact, this particular loss-of-function mutation would be dominant.

Where does a problem with genetic screening arise?

A problem arises if we wish to study essential genes that are absolutely required for fundamental cell processes such as RNA synthesis or cell division. Defects in those genes are usually lethal, which means that special strategies are needed to isolate and propagate such mutants: if the mutants cannot be bred, their genes cannot be studied.

Describe the process of fertilizing the egg.

Although many sperm may bind to an egg, only one normally fuses with the egg plasma membrane and introduces its DNA into the egg cytoplasm. The control of this step is especially important because it ensures that the fertilized egg called a zygote will contain two, and only two, sets of chromosomes.

In human oocytes, the cells that give rise to the egg, on average have many cross-over events occur?

An average of two to three cross-over events occur within each bivalent.

Because of random reassortment of maternal and paternal homologs, an individual could, in principle, produce have many genetically different gametes? Why is the number actually much greater than this?

An individual could in principle produce 2^n genetically different gametes, where n is the haploid number of the chromosomes. With 23 chromosomes to chose from, each human, could in theory produce 2^23 or 8.4x10^6 genetically distinct gametes. The actual number of different gametes each person can produce is much greater than that because the crossing-over that takes place during meiosis provides a second source of randomized genetic reassortment.

Why are loss-of-function genes normally recessive?

An organism in which both alleles of a gene bear loss-of-function mutations will generally display an abnormal phenotype. By, contrast, the heterozygote, which possesses on mutant allele and one normal "wild-type" allele, generally makes enough active gene product to function normally and retain a normal phenotype type. Thus, loss-of-function mutations are usually recessive because, for most genes, decreasing the normal amount of gene product by 50% has little impact.

Why does aneuploidy occur less in human sperm?

Aneuploidy occurs less often in human sperm, perhaps because sperm development is subjected to more stringent quality control than egg development. If meiosis goes wrong in male cells, a cell-cycle checkpoint mechanism is activated, arresting meiosis and leading to cell death by apoptosis.

How has genetic maps been crucial for isolating and characterizing mutant genes responsible for human genetic disease?

By measuring how frequently genes are co-inherited, geneticists can determine whether they reside on the same chromosome and, if so, how far apart they are. These measurements of genetic linkage have been used to map relative positions of the genes on each chromosome of many organisms. Such genetic maps have been crucial for isolating and characterizing mutant genes responsible for human genetic diseases such as cystic fibrosis.

What happens to the synaptonemal complex and bivalents by the time that meiotic prophase ends?

By the time the meiotic prophase ends, the synaptonemal complex has disassembled, allowing the homologs to separate along most of their length. But each bivalent remains held together by at least one chiasma, or plural chiasmata, which is shaped like a cross. Each chiasma corresponds to a crossover between two non-sister chromatids. Most bivalents contain more than one chiasma, indicating the multiple crossovers occur between homologous chromosomes.

Why are haplotype blocks important?

Certain DNA sequence, and their associated polymorphisms, have been inherited in linked groups, with little genetic rearrangement across generations. These are the haplotype blocks. Like genes that exist in different allelic forms, haplotype blocks also come in a limited number of variants that are combination of DNA polymorphisms passed down from a particular ancestor long ago. Provide clues to our evolutionary history.

What is a complementation test and what can it reveal?

Complementation test are a genetic experiment whether two mutations that are associated with the same phenotype lie in the same gene or a different gene.

How does chromosome pairing and crossing-over ensure the proper segregation of homologs?

Crossing-over during meiosis is required for the correct segregation of the two duplicated homologs into separate daughter nuclei. 1. Before anaphase 1, the two poles of the spindle pull on the duplicated homologs in opposite directions, and the chiasmata resist this pulling. In doing so, the chiasmata help to position and stabilize bivalents at the metaphase plate. 2. Cohesin proteins keep the sister chromatids glued together along their entire length at meiosis I. 3. At the start of Anaphase I, the cohesin proteins are suddenly degraded. This release allows the arms to separate and the recombined homologs to be pulled apart. 4.If the arms were not released this way, the duplicated maternal and paternal homologs would remain tethered to one another by the homologous DNA segments they had exchanged and would not separate during Anaphase I.

What helps hold maternal and paternal homologs together and facilitates crossing-over?

Crossing-over is a complex, multistep process that is facilitated by the formation of a synaptonemal complex. As the duplicated homologs pair, this elaborate protein complex helps hold the bivalent together and align the homologs so that the strand exchange can readily occur between the non-sister chromatids. Each of the chromatids in a duplicated homolog, very long DNA double helices, can form a crossover with either (or both) of the chromatids from the other chromosome in the bivalent.

Discuss the importance of crossing-over in meiosis?

Crossing-over that takes place during meiosis are a major source of genetic variation in sexually reproducing species. By scrambling the genetic constitution of each of the chromosomes in the gamete, crossing-over helps to produce individuals with novel alleles. But crossing-over has a second important role in meiosis: it helps ensure that the maternal and paternal homologs will segregate from one another correctly at the first meiotic division.

What are bivalents?

Each pairing structure forms a structure called bivalent, in which all four sister chromatids stick together until the cell is ready to divide.

Why do the haploid gametes contain reassorted genetic information?

Even though they share the same parents, no two siblings are genetically the same (unless they are identical twins). These genetic differences are initiated long before sperm meets egg, when meiosis I produce two kinds of randomizing genetic reassortment. 1. Maternal and paternal chromosomes are shuffled and dealt with randomly through meiosis I. Chromosomes are carefully distributed so that each gamete receives one and only one copy of each chromosome, the choice between the maternal and paternal homolog is by chance. Each gamete contains the maternal version of some chromosomes and the paternal versions of others. 2. Crossing-over that takes place during meiosis provides the second source of randomized genetic reassortment. Between two and three crossovers occur on average between each pair of human homologs, generating new chromosomes with novel assortments of maternal and paternal alleles. Because crossing-over occurs at more or less random sites along the length of a chromosome, each meiosis will produce four sets of entirely novel chromosomes.

What process does fertilization mark?

Fertilization marks the process by which a single-cell zygote initiates the developmental program that directs the formation of a new individual.

What provides the physical basis for Mendel's laws of heredity?

Genes are carried on chromosomes that parceled out during the formation of gametes and then brought together in novel combinations in the zygote at fertilization. Chromosomes, therefore, provide the physical basis for Mendel's laws, and their behavior during meiosis and fertilization explains these laws perfectly.

Unlike the majority of cells in a diploid organism, the specialized cells that carry out the central process in sexual reproduction are different. What are this is difference and what are they called?

Haploid describes a cell that carries only one set of chromosomes, such bacterium and sperm cells. They are called gametes which is a cell type in a haploid organism that carries only one set of chromosomes and is specialized for sexual reproduction. Examples are sperm or egg cells which are also called germ cells.

How can we study genes that are essential genes?

If the organism is diploid and the phenotype is recessive, their is a simple solution. Individuals that are heterozygous for the mutation will have a normal phenotype and can be propagated. When they are mated with one another, 25% of the progeny will be homozygous mutants and will show the lethal mutant phenotype; 50% will be heterozygous carriers of the mutation like their parents and can be used to maintain the breeding stock.

Why is the sorting of chromosomes that takes place during meiosis a remarkable feat of molecular book keeping?

In humans, each meiosis requires the starting cell to keep track of 92 chromosomes (23 pairs, each of which is duplicated), handing out one complete set to each gamete. Not surprisingly, mistakes can occur in the distribution of chromosomes during this elaborate process.

What mechanism makes sure only on sperm cell injects its DNA into the egg cytoplasm?

In one mechanism, the first successful sperm triggers the release of a wave of Ca2+ ions in the egg cytoplasm. This flood of Ca2+ in turn triggers the secretion of enzymes that cause a "hardening" of the zona pellucida, which prevents "runner up" sperm from penetrating the egg. The Ca2+ wave also helps trigger the development of the egg.

The picture we just painted about meiosis is greatly simplified meaning it leaves out a crucial feature about bivalents. Discuss homologous recombination and crossing-over between bivalents.

In sexually reproducing organisms, the pairing of the maternal and paternal chromosomes is accompanied by homologous recombination a process in which two identical or very similar nucleotides exchange genetic information. Differing from DNA repair, a similar process takes place when homologous chromosomes pair during the long prophase I of meiosis. Recombination occurs between non-sister chromatids in each bivalent, rather than between the identical sister chromatids within each duplicated chromosome. In this process, the maternal and paternal homologs can physically swap homologous chromosomal segments, an event called cross-over.

What is Mendel's second law of heredity?

Law of independent assortment. This law states that the factors controlling different characteristics are inherited independently of each other. Think pea color vs pea shape.

What is Mendel's first law of heredity?

Law of segregation. It states that the two alleles for each trait separate (or segregate) during gamete formation and then unite at random, one from each parent, at fertilization.

How does each cell carry two copies of each gene? Is there an exception?

Maternal and Paternal chromosomes are homologous chromosomes meaning they carry the same set of genes. Genes on sex chromosomes may only be present in only one copy.

What was the outcome of Mendel's experiments?

Mendel was able to proposed that the inheritance of traits is governed by hereditary factors (genes) and that these factors come in alternative versions that account for the variations seen in inherited characteristics. Such alternative version of genes are now called alleles, and the whole collection of alleles possessed by an individual is called its genotype.

What was Mendel's major conceptual breakthrough regarding inherited characteristics?

Mendel's major conceptual breakthrough was to propose that for each characteristic, an organism must inherit two copies, or alleles, of each gene. One from its mother and one from its father. An individual that possesses two identical alleles is said to be homozygous for that trait. An individual that possesses two different alleles is said to be heterozygous for that trait.

How are mutagens used in genetics?

Mutagens are generated artificially with agents that damage DNA. Different mutagens generate different types of DNA damage. Mutagens made the process of finding interesting phenotypes more efficient.

Compare and contrast loss of function and gain of function genes.

Mutations produce heritable changes in DNA seq. They can arise in various ways (Review chapter 6) and can be classified by the effect they have on gene function. Mutations that reduce or eliminate the activity of a gene are called loss-of-function mutations. Mutations that increase the activity of a gene or its product, or result in the gene being expressed in inappropriate circumstances are called gain-of-function mutations.

What is it called when homologs fail to separate properly? Can you give an example?

Occasionally, homologs fail to separate properly and phenomenon known as nondisjunction occurs. As a result, some of the haploid cells that are produced lack a particular chromosome, while others have had more than one copy. Upon fertilization, such gametes from abnormal embryos, most of which die. Some, however, survive. Down Syndrome, for example, is a disorder associated with cognitive disability and characteristic physical abnormalities are caused by an extra copy of chromosome 21 during meiosis I, giving rise to a gamete that contains two copies of that chromosome instead of one. When this abnormal gamete fuses with a normal gamete in fertilization, the resulting embryo contains three copies of chromosome 21 instead of two.

How does the sperm fuse to the egg?

Of the 300 million human sperm ejaculated during sexual intercourse, only about 200 reach the site of fertilization in the oviduct. Sperm are attracted to an ovulated egg by chemical signals released by both the egg and the supporting cells that surround it. Once a sperm finds the egg, it must migrate through a protective layer of cells and then bind to, and tunnel through, the egg coat, called the zona pellucida. Finally, the sperm, must bind to and fuse with the underlying egg plasma membrane.

Are bivalents stable?

Once formed, bivalents are very stable as they can remain associated throughout the meiotic prophase, a stage that can last for years. The initial association depends on an interaction between matching maternal and paternal DNA sequences at numerous sites that are widely dispersed along the homologous chromosomes.

If the maternal and paternal homologs carry the same genes, why should such chromosomal assortment matter?

One answer is that although the set of genes on each homolog is the same, the paternal and maternal version of each gene is not. Gene occur in variant versions, called alleles, with slightly different DNA sequences.

What are pedigrees and how are they used?

Pedigrees show the phenotype of each family member for a relevant trait. The Figures show the pedigree for a family that harbors a recessive allele for deafness. It also illustrates an important practical consequence of Mendel's laws: marriages between related individuals create a greatly increased risk of producing children that are homozygous for a deleterious recessive mutation.

What is the reason for the high rate of miscarriages in humans?

Regardless of whether of this segregation error occurs in the sperm or the egg, nondisjunction is thought to be one reason for the high rate of miscarriages.

How does sexual reproduction produce novel chromosome combinations?

Sexual reproduction produces novel chromosomes during meiosis, the maternal and paternal chromosomes sets in the diploid germline cells are partitioned into the single chromosome sets of the gametes. Each gamete will receive a mixture of maternal homologs and paternal homologs; when the genomes of two gametes combine during fertilization, they produce a zygote with a unique chromosomal complement.

What is the male/female gametes?

The female gamete is called the egg, which is large and non motile. The male gamete is called sperm and is small and motile.

Why can genes that lie on the same chromosome segregate independently by crossing-over? Is there an exception?

The independent segregation of different traits does not necessarily require that the responsible genes lie on different chromosomes. If two genes are far enough away from each other on the same chromosome, they will also sort independently, because crossing-over occurs during meiosis. This genetic exchange can separate alleles that were formerly together on the same chromosome, causing them the segregate into different gametes, if they are far apart they segregate independently. Not all genes segregate independently as per Mendel's second law. If the genes lie close together on a chromosome, they are likely to be inherited as a unit.

What is the process that the bivalent will segregate?

The maternal and paternal homologs (bivalents) will separate during meiosis I, and the individual sister chromatids will separate during meiosis 2.

Describe the maternal and paternal chromosomes.

The maternal and paternal versions of every chromosome are also called the maternal and paternal homologs, or homologous chromosomes. This means they carry the same set of genes.

When is the process of fertilization complete?

The process of fertilization is not complete until the two haploid nuclei (called pronuclei) come together and combine their chromosomes into a single diploid nucleus. Soon after the pronuclei fuse, the diploid cell begins to divide, forming a ball of cells that (through repeated rounds of cell division and differentiation) will give rise to an embryo and, eventually, an adult organism.

For almost all multicellular animals, including vertebrates, most of the life cycle is spent in the diploid state. The haploid cells exist only briefly and are highly specialized for their function as genetic ambassadors. How are these haploid cells created?

These haploid gametes are generated from diploid precursor cells by a specialized form of reductive division called meiosis. This precursor cell lineage is called the germline. The somatic cells forming the rest of the animal's body ultimately leave no progeny of their own. They exist, in effect, only to help the cells of the germline survive and propagate.

How does the sperm and egg interact?

These two dissimilar haploid gametes join together to regenerate diploid cells, called the fertilized egg, or zygote, which as homologous chromosomes from both the mother and the father. The zygote thus produced develops into a new individual with a diploid set of chromosomes that is distinct from that of either parent.

Common variants can be scattered throughout the genome but they are not scattered randomly or even independently. How do they tend to travel?

They tend to travel in groups called haplotype blocks: a combination of alleles or other DNA markers that has been inherited as a unit, undisturbed by genetic recombination, across many generations.

How are maternal and paternal chromosomes shuffled and dealt with randomly through meiosis I?

This random assortment depends solely on the way each bivalent happens to be positioned when it lines up on the spindle during metaphase of meiosis I. Whether the maternal or paternal homolog is captured by the microtubules from one pole or the other depends on which way the bivalent is facing when the microtubules connect to its kinetochore. Because the orientation of each bivalent at the moment of capture is completely random, the assortment of maternal and paternal chromosomes is random as well.

How does the second meiotic division (meiosis II) produce haploid daughter nuclei?

To separate the sister chromatids and produce cells with a haploid amount of DNA, the second round of division, meiosis II, follows soon after the first w/out further DNA replication or any significant interphase period. A meiotic spindle forms and the kinetochores on each pair of sister chromatids now attach to kinetochore microtubules that point in opposite directions. At, Anaphase of meiosis II, the remaining, meiosis-specific cohesins (located at centromere) are degraded, and the sister chromatids are pulled further apart. See the movie on the eBook.

What is fertilization?

Union of sperm and egg to form a new cell with a diploid set of chromosomes.

How does sexual reproduction create genetic diversity?

What makes individuals within a species genetically unique is the inheritance of different combinations of alleles. And with its cycles of diploidy, meiosis, haploidy, and cell fusion, sex breaks up old combinations of alleles and generates new ones. Sexual reproduction also generates genetic diversity through a second mechanism called homologous recombination.