Gene Expression: Transcription and Translation

Protein synthesis requires two steps: transcription and translation

Transcription is when RNA is made from DNA. The information is copied from one molecule to the other. The DNA sequence is copied by a special enzyme calle d RNA polymerase to make a matching RNA strand.

RNA polymerase – is responsible for a process called transcription, which by producing RNA from DNA, takes the first step in reading the blueprint of life that is encoded in all of our genes

Nucleotides are chemical compounds, the building blocks of the nucleic acids RNA and DNA.

A nucleotide is composed of a nucleobase (nitrogenous base), a five-carbon sugar (either ribose or 2-deoxyribose), and onephosphate group.

 Nucleotides contain either a purine  or a pyrimidine base. 

Ribonucleotides are nucleotides in which the sugar is ribose. 

Deoxyribonucleotides are nucleotides in which the sugar is deoxyribose

In DNA, the purine bases are adenine and guanine, while the pyrimidines are thymine and cytosine. 

RNA uses uracil in place of thymine. 

Adenine always pairs with thymine by 2 hydrogen bonds,

while guanine pairs with cytosine through 3 hydrogen bonds,

Kinds of RNA

RNA has a variety of different functions in the cell. Three of these are listed below.

Messenger RNA (mRNA)

Messenger RNA contains genetic information. It is a copy of a portion of the DNA.

It carries genetic information from the gene (DNA) out of the nucleus, into the cytoplasm of the cell where it is translated to produce protein.

Ribosomal RNA (rRNA)

This type of RNA is a structural component of the ribosomes. It does not contain a genetic message.

Transfer RNA (tRNA)

Transfer RNA functions to transport amino acids to the ribosomes during protein synthesis.

Small nuclear RNA (snRNA)

These strands of RNA are complexed with protein producing small nuclear ribonucleoproteins (snRNP).

 

DNA contains codes

The simplistic diagram below illustrates the concept that three bases in DNA code for one amino acid. The DNA code is copied to produce mRNA. Later in this chapter, we will learn that RNA may be modified. The order of amino acids in the polypeptide is determined by the sequence of 3-letter codes in mRNA.

Eukaryotic genes contain regions that are not translated into proteins. These regions of DNA are called introns (intervening sequences) and must be removed from mRNA by a process called RNA splicing. Their function is not well understood.

The remaining portions of DNA that are translated into protein are called exons (expressed). After intron-derived regions are removed from mRNA, the remaining fragments- derived from exons- are spliced together to form a mature mRNA transcript.

The nucleus is the site of mRNA transcription

In addition to the production of rRNA and tRNA, the nucleus is responsible for producing messenger RNA. This process is called transcription

The ribosome is the site of protein translation

The ribosome subunits attach to the mRNA and together slide along the RNA. As the subunits pass along the RNA, transfer RNAs deliver amino acids as coded by the sequence of nucleotides in the RNA. The ribosome proteins and ribozymes catalyze the formation of the peptide bond between the amino acids to provide the primary structure of the developing polypeptide.

Translation is the second part of protein biosynthesis (the making of proteins). It is part of the process of gene expression.

Before translation comes:

transcription produces a chain of introns and exons.

RNA splicing by spliceosomes which remove introns, and

formulate the messenger RNA from exons.

In eukaryotes, translation happens on the ribosomes in the cytoplasm and in the endoplasmic reticulum. In bacteria, translation happens in the cell cytoplasm: they have no nucleus.

Is a human body cell diploid or haploid?

Diploid.

Only gametes are haploid. Your cells have DNA, and it comes in the form of chromosomes. There are 23 different chromosomes in a set.

In a diploid cell, there are two sets, i.e. two copies of each chromosome, making for a total of 46 chromosomes in that cell.

In a haploid cell, there's only one copy of each chromosome. Most of your body's cells are diploid. Only the gametes, the sperm (in men) and the ova or unfertilized eggs (in women), and the cells that divide to form them (secondary oocytes) are haploid.

Homologous Chromosomes

Homologous chromosomes are two chromosomes that are the same. This happens because diploid organisms have two of each chromosome. Each of the pairs is a homologous pair.

Mitosis

Mitosis produces two daughter cells that are identical to the parent cell.  If the parent cell is haploid (N), then the daughter cells will be haploid.   If the parent cell is diploid, the daughter cells will also be diploid. 

N --> N

2N --> 2N

This type of cell division allows multicellular organisms to grow and repair damaged tissue.

Meiosis

Meiosis produces daughter cells that have one half the number of chromosomes as the parent cell. 

2N --> N

Meiosis enables organisms to reproduce sexually. Gametes (sperm and eggs) are haploid.

Meiosis is necessary in sexually-reproducing organisms because the fusion of two gametes (fertilization) doubles the number of chromosomes.

Meiosis involves two divisions producing a total of four daughter cells.

Meiosis functions to reduce the number of chromosomes to one half. Each daughter cell that is produced will have one half as many chromosomes as the parent cell.

Meiosis is part of the sexual process because gametes (sperm, eggs) have one half the chromosomes as diploid (2N) individuals.

Phases of Meiosis

There are two divisions in meiosis; the first division is meiosis 1 and the second is meiosis 2. The phases have the same names as those of mitosis. A number indicates the division number (1st or 2nd):

meiosis 1: prophase 1, metaphase 1, anaphase 1, and telophase 1

meiosis 2: prophase 2, metaphase 2, anaphase 2, and telophase 2

 

In animals, meiosis occurs only when gametes (sperm, eggs) are formed.

Letters Can Represent GenesThe characteristics studied by Mendel were due to single genes. On the pair of chromosomes diagrammed below, the letter "A" represents a gene for yellow seeds. The letter "a" on thehomologous chromosome represents a gene for green seeds. By convention, upper case letters are used to represent dominant genes and lower case letters are used for recessive genes.

Heterozygote (also called hybrid) refers to an individual that has two different forms of the gene. Example: Aa 

Homozygote refers to an individual that has two identical genes. Example: AA or aa

A hybrid is a heterozygote. Example: Aa

Principle of Segregation

Mendel’s principle of segregation states that paired factors (genes) separate during gamete formation (meiosis). Because the pair of genes (Aa, AA, or aa) separate, one daughter cell will contain one gene and the other will contain the other gene. (See diagram above.)

Gametes

Because pairs of chromosomes separate during meiosis I, gametes are haploid, that is, they carry only one copy of each chromosome. An Aa individual therefore produces two kinds of gametes: A and a.

Below: An "AA" individual produces all "A" gametes. Similarly, an "aa" individual produces all "a" gametes

Individual (genotype) Type of gametes produced

AA all gametes will contain an "A"

Aa 1/2 will contain "A" and 1/2 will contain "a"

aa all "a" gametes

 Genotype   Phenotype 

AA or Aa Yellow

aa Green

Genotype and Phenotype

The genetic makeup of an individual is referred to as itsgenotype. Because the plants are diploid, two letters can be used to write the genotype. In this case, the genotype of the P1 plants was YY; the genotype of the F1 plants was

Yy.The characteristics of an individual are its  phenotpye. This word refers to what the individual looks like so ddjectives are used to write the phenotype. For example, "yellow" or "tall" are phenotypes.

Dosage Compensation

Although females have twice as many X-linked genes, the amount of protein produced by these genes is the same in females as it is in males.

Reduced protein production (called dosage compensation) occurs as a result of inactivating one X chromosome by coiling and condensing it. When condensed, it cannot be transcribed, that is, it cannot be used to produce mRNA.

Condensed X chromosomes, called Barr bodies, are visible using ordinary light microscope techniques.

The table below shows the number of Barr bodies in normal cells and in the cells of people with an abnormal number of X chromosomes. Normal males do not have Barr bodies because they only have one X chromosome.

Genetic Condition # Barr Bodies per Cell

normal male 0

normal female 1

XXX female 2

XXXX female 3

XXY (Klinefelter male) 1

Karyotypes Karyotypes are prepared using cells from amniocentesis, chorionic villi

sampling, or white blood cells.

Cells are photographed while dividing. cells are normally stained so that banding patterns appear on the chromosomes. The bands make it easier to identify the chromosomes. Banding patterns are not visible in the photograph below due to the staining technique.

• Pictures of the chromosomes are cut out and arranged in pairs according to size and banding patterns.

• Karyotypes can be used to determine if there is an abnormality in chromosome number or structure

NondisjunctionNondisjunction occurs when chromosomes fail to "disjoin" during meiosis or mitosis.

Aneuploidy

Cells that have extra chromosomes or chromosomes missing are aneuploid. Two types of aneuploidy are discussed below.

Monosomy refers to a condition in which there is one chromosome is missing. It is abbreviated 2N - 1. For example, monosomy X is a condition in which cells have only one X chromosome.

A trisomy has one extra chromosome and is abbreviated 2N + 1. Trisomy 21 is an example of a trisomy in which cells have an extra chromosome 21.

Monosomies and trisomies usually result from nondisjunction during meiosis but can also occur in mitosis. They are more common in meiosis 1 than meiosis 2.

They are generally lethal except monosomy X (female with one X chromosome) and trisomy 21 (Down’s Syndrome).

Affected individuals have a distinctive set of physical and mental characteristics called a syndrome. For example, trisomy 21 is Down syndrome

Oogenesis is more likely to continue than spermatogenesis when a chromosomal abnormality occurs. As a result, 80% to 90% of aneuploid (extra chromosomes or chromosomes missing) fetuses are due to errors in meiosis I of the female.

Incidence of Genetic Abnormalities

Maternal Age

At 25 years, 17% of secondary oocytes may have chromosomal abnormalities. At 40 years, up to 74% may contain abnormalities.

Spontaneous Abortion (Miscarriage)

Two-thirds of all pregnancies are lost. These miscarriages are called spontaneous abortions.

Genetic mutation causes an estimated 60% of these spontaneous abortions.

Autosomal Abnormalities

Nine percent of spontaneous abortions are trisomy 13, 18, or 21; but 0.1% of newborns have these trisomies.

Down Syndrome

Down syndrome is trisomy 21. It is characterized by intellectual disability, an abnormal pattern of palm creases, a flat face, sparse, straight hair, and short stature. People with Down syndrome have a high risk of having cardiac anomalies, leukemia, cataracts, and digestive blockages.

Life expectancy of Down syndrome individuals is 55 years.

The gene responsible for Alzheimer’s is on chromosome 21. Down’s are at increased risk for developing Alzheimer’s.

Down Syndrome is associated with maternal age. Older women, particularly those

Trisomy 18 (Edward Syndrome)

The incidence of Trisomy 18 is approximately 1 out of every 3000 live births.

older than 40, are more likely to have a Down Syndrome child.

Trisomy 13 (Patau Syndrome)

The incidence of Trisomy 13 is is approximately 1 out of 16,000 live births.

Polyploidy

Polyploidy is a condition in which there is more than 2 sets of chromosomes.

Triploids (3N), tetraploids (4N), pentaploids (5N) etc. are polyploids.

Polyploidy in Humans

Polyploids have defects in nearly all organs.

Most die as embryos or fetuses. Occasionally an infant survives for a few days.

XXX - Triple-X Syndrome (also XXXX and XXXXX)

Triple-X individuals are tall and thin and have menstrual irregularities. Their IQ is in the normal range but it is slightly reduced.

The incidence of Triple-X Syndrome is 1 in 1,500 female births.

Additional X chromosomes are associated with an increased intellectual disability.

XXY - Klinefelter Syndrome (also XXXY)

Males with two or more X chromosomes have Klinefelter Syndrome.

The incidence of Klinefelter Syndrome is 1 in 1000 male births.

Symptoms include reduced sexual maturity and secondary sexual characteristics, breast swelling (gynecomastia), and infertility. Klinefelter males are slow to learn and individuals with additional X’s (XXXY) may be intellectually handicapped.

XYY - Jacob Syndrome

Most XYY males are normal and are unaware of an additional chromosome. XYY males tend to be tall and may have speech and reading problems.

Abnormalities of the Sex Chromosomes

Turner Syndrome - XO

Characteristics of Turner syndrome include the following:

Sexually underdeveloped

Short stature

Folds of skin on the back of the neck

Wide-spaced nipples

Narrow aorta

Pigmented moles

97% die before birth

Malformed elbows

Infertile

Normal Intelligence

The incidence of Turner syndrome is 1 in 2000 female births.

Turner syndrome individuals that are treated with hormones lead fairly normal lives.

What are Dominant and Recessive?

The terms dominant and recessive describe the inheritance patterns of certain traits. That is, they describe how likely it is for a certain phenotype to pass from parent offspring.

Sexually reproducing species, including people and other animals, have two copies of each gene. The two copies, called alleles, can be slightly different from each other. The differences can cause variations in the protein that’s produced, or they can change protein expression. Proteins affect traits, so variations in protein activity or expression can produce different phenotypes.

A dominant allele produces a dominant phenotype in individuals who have one copy of the allele, which can come from just one parent. For a recessive allele to produce a recessive phenotype, the individual must have two copies, one from each parent. An individual with one dominant and one recessive allele for a gene will have the dominant phenotype. They are generally considered “carriers” of the recessive allele: the recessive allele is there, but the recessive phenotype is not.

Dominance in genetics is a relationship between alleles of one gene, in which one allele is expressed over a second allele at the same locus. The first allele isdominant and the second allele is recessive. For genes on an autosome (any chromosome other than a sex chromosome), the alleles and their associated traits are autosomal dominant or autosomal recessive.

Inheritance patterns

Sickle-cell disease is an inherited condition that causes pain and damage to organs and muscles. Instead of having flattened, round red blood cells, people with the disease have stiff, sickle-shaped cells.

The disease has a recessive pattern of inheritance: only individuals with two copies of the sickle-cell allele have the disease. People with just one copy are healthy.

Autosomal Dominant

Severe dominant diseases are rare because carriers die before they get a chance to reproduce and pass on the disease to their offspring.

Heterozygotes (Aa) have the trait.

Children with the trait have at least one parent that has the trait.

Both males and females are affected equally.

Neurofibromatosis (NF)

Neurofibramatosis is actually three separate genetic diseases that cause benign tumors to grow on nerves.

The incidence is 1 in 3000 newborns.

The gene is on chromosome 17.

Huntington’s Disease

The brain cells of Huntington's victims slowly degenerate, producing jerking muscles, slurred speech, swallowing difficulty, loss of balance, mood swings, reasoning and memory loss, incapacitation, and eventually death (usually from pneumonia or heart failure).