Cell Cycle, Interphase Stages

The Cell Cycle

• The cell cycle is the series of stages from a eukaryotic cell's first division to when resulting daughter cells divide.
• Key events prior to the following division include cell growth, organelle duplication, and DNA replication.
• The two main stages of the cell cycle are interphase and the mitotic stage.
• Interphase includes several stages
• The mitotic stage includes mitosis and cytokinesis.

Stages of Interphase

• Interphase includes the G1, S, and G2 stages and makes up about 90% of the cell cycle.
• In the G1 stage, the cell recovers from the previous division and increases its organelles, size, and materials for DNA synthesis.
• During the S stage, DNA synthesis and replication occur along with the production of associated proteins.
• Chromosomes enter the S phase with one chromatid each but leave with two identical sister chromatids each.
• Sister chromatids remain attached until separated during mitosis.
• The G2 phase, between DNA replication and mitosis onset, involves the synthesis of necessary proteins, including microtubules, for division.

Chromosome Number

• The diploid (2n) number includes two sets of chromosomes of each type; humans have 23 types of chromosomes.
• Each chromosome type is represented twice in diploid body cells; sperm and eggs have one of each type, termed haploid (n).
• Humans' haploid (n) number is 23.
• Each chromosome type has two representatives.
• The total chromosome number is 2n = 46 in each nucleus.
• One set of 23 chromosomes comes from the individual's father (paternal).
• The other set comes from the individual's mother (maternal).

Chromosome Duplication

• During interphase, a cell prepares for division and duplicates organelles including the centrosome.
• At the end of the S stage, each chromosome consists of two identical double-helical DNA molecules.
• Sister chromatids are genetically identical chromosomes attached at a single point called the centromere.
• During Mitosis, centromeres holding sister chromatids together separate.
• Sister chromatids separate, each becoming a daughter chromosome.
• Daughter chromosomes are distributed to opposite daughter nuclei.

Mitosis

• Mitosis involves multiple phases: Early Prophase, Prophase, Prometaphase, Metaphase, Anaphase, and Telophase

Overview of Meiosis

• Meiosis is a special type of cell division used only for sexual reproduction; it reduces the original chromosome number and then fertilization restores in the offspring.
• Chromosomes are replicated in the S stage of interphase prior to fertilization
• Parents are diploid (2n).
• Meiosis produces haploid (n) gametes, which have a single set of chromosomes.
• Gametes fuse to form a diploid (2n) zygote.
• The zygote becomes the next diploid (2n) generation.
• If meiosis events go wrong, gametes may contain the wrong number of chromosomes.

Homologous Chromosomes and Alleles

• Homologous chromosomes have genes controlling the same trait at the same position, with each gene occurring in duplicate.
• There is a maternal copy of the gene from the mother.
• There is also a paternal copy of the gene from the father.
• Multiple variant forms of many genes exist in a large population
• Homologous copies of a gene encode identical or different genetic information.
• The different variants are called alleles.
• An individual may have two:
  • Identical alleles for a specific gene on both homologues (homozygous).
  • They may have a maternal allele which differs from the corresponding paternal allele (heterozygous).
• An example of this involves the presence a gene coding for short fingers on one homologue and a gene coding for long fingers at the same location on the other.

How Meiosis Works

• Meiosis involves two nuclear divisions.

Meiosis I

• Chromosomes are replicated prior to meiosis I, with each consisting of two identical sister chromatids
• Homologous chromosomes pair up in synapsis and recombine or exchange genetic material.
• Homologous pairs align against each other side by side at the metaphase plate.
• The two members of a homologous pair separate.
• Each daughter cell receives one duplicated chromosome from each pair, reducing total chromosome number from 2n to n.

Meiosis II

• DNA is not replicated between meiosis I and II.
• Sister chromatids separate and move to opposite poles.
• The four daughter cells contain one daughter chromosome from each pair
• Each daughter chromosome includes a single chromatid
• The daughter cells are haploid

Genetic Variation

• Genetic variation is essential for a species to evolve and adapt to changing environments.
• Genetic variation in asexually reproducing organisms depends on mutations.
• Meiosis brings about genetic variation in two ways: crossing-over between homologous chromosomes and independent assortment of homologous chromosomes.

Crossing-Over

• Crossing-over exchange genetic material between non-sister chromatids during meiosis I.
• At synapsis, a nucleoprotein lattice, the synaptonemal complex, appears between homologues, holding them together and aligns DNA of non-sister chromatids.
• Allows crossing-over, and then, homologues separate and distribute to different daughter cells.

Independent Assortment

• When homologous chromosome pairs align at the metaphase plate:they separate randomly.
• Maternal or paternal homologue can be oriented toward either pole of the mother cell, causing a random mixing of alleles into gametes.
• For a cell with three pairs of homologous chromosomes, the possible chromosome orientations are 23, or 8 combinations of maternal and paternal chromosomes.

Genetic Variation Significance

• Asexual reproduction produces genetically identical clones
• Sexual reproduction causes genetic recombinations among members of a population.
• Humans have 23 pairs of chromosomes, therefore the possible chromosomal combinations are 233 or 8388608, assuming no crossing-over
• Asexual reproduction is advantageous when the environment is stable.
• However, if the environment changes, genetic variability introduced by sexual reproduction may be advantageous.
• Offspring may have a better chance of survival.
• For example, if the temperature rises due to climate change, an animal with less fur or reduced body fat would have an advantage.

Meiosis Compared to Mitosis

Meiosis

• Requires two nuclear divisions.
• Chromosomes synapse and cross-over between each other.
• Centromeres survive Anaphase I.
• Halves chromosome number.
• Produces four daughter nuclei.
• Produces daughter cells genetically different from the parent and each other.
• Used only for sexual reproduction.

Mitosis

• Requires one nuclear division
• Chromosomes do not synapse or cross over.
• Centromeres dissolve in mitotic anaphase.
• Preserves chromosome number.
• Produces two daughter nuclei.
• Produces daughter cells genetically identical to the parent and to each other.
• Used for asexual reproduction and growth.

Changes in Chromosome Number and Structure

• Typically, meiosis proceeds normally.
• Euploidy is the correct number of chromosomes in a species.
• Aneuploidy is a change in the chromosome number.
• A karyotype displays chromosomes arranged by size, shape, and banding pattern observing aneuploidies.
• Aneuploidy results from nondisjunction, the failure of chromosomes to separate, and can occur in meiosis I or II resulting in the gain or loss of chromosomes. Monosomy = only one of a particular type of chromosome.
• Trisomy = three of a particular type of chromosome.

Dominant and Recessive Alleles

• Dominant and recessive alleles represent DNA sequences that code for proteins.
• The dominant allele codes for the protein associated with the normal gene function in the cell
• The recessive allele represents a “loss of function."
• During meiosis I, the homologous chromosomes separate.
• The two alleles separate from each other.
• Meiosis explains Mendel's law of segregation, revealing why only one allele for each trait is in a gamete.

Mendelian Patterns of Inheritance and Human Disease

• Genetic disorders are medical conditions caused by alleles inherited from parents.
• An autosome is any chromosome other than a sex chromosome (X or Y).
• Genetic disorders caused by genes on autosomes are called autosomal disorders.
• Some genetic disorders are autosomal dominant; an individual with AA or Aa has the disorder, while an individual with aa does NOT have the disorder.
• Other genetic disorders are autosomal recessive: individuals with AA or Aa, who is a carrier, do NOT have the disorder but an individual with aa DOES have the disorder.

Genetic Material

• DNA and proteins were candidates for the hereditary material.
• Proteins contain 20 amino acids that can be sequenced in different ways.
• DNA and RNA each contain only four types of nucleotides.

Requirements for Genetic Material

• Must be able to store genetic information.
• Must be stable and able to be replicated accurately during cell division and transmitted from generation to generation.
• Must be able to undergo mutations to provide genetic variability.
• Researchers showed that DNA can fulfill all these functions.

Chargaff's Rules

• The amounts of A, T, G, and C in DNA:are constant among members of the same species but vary from species to species.
• In each species, there are equal amounts of A and T and equal amounts of G and C.

DNA Replication Overview

• Unwinding or separating the two strands of the parental DNA molecule by the DNA helicase enzyme
• Single-stranded binding proteins (SSB) attach to newly separated DNA and prevent helix from re-forming.
• Complementary base pairing between a new nucleotide and a nucleotide on the template strand.
• DNA primase places short primers on the strands to be replicated.
• Polymerase recognizes RNA and begins DNA synthesis.
• The two strands are replicated differently: leading and lagging strands.
• DNA ligase joins nucleotides in the lagging strand to form the new strand.
• Each daughter DNA molecule contains one old and one new strand.

RNA Carries Information

Gene Expression

• DNA in genes specifies information, but information is not structure and function.
• Genetic information is expressed into structure and function through protein synthesis.

Genetic Information Structure and Function

• DNA in a gene determines the sequence of nucleotides in an RNA molecule.
• RNA controls the primary structure of a protein.
• The flow of genetic information is from DNA to RNA to protein to an observed trait.

Major Classes of RNA

• RNA is a polymer of RNA nucleotides.
• RNA nucleotides contain the sugar ribose instead of deoxyribose.
• RNA nucleotides are of four types: uracil (U), adenine (A), cytosine (C), and guanine (G).
• Uracil (U) replaces thymine (T) of DNA.

Types of RNA

• Messenger (mRNA) takes a message from DNA in the nucleus to ribosomes in the cytoplasm.
• Transfer (tRNA) transfers the appropriate amino acid to the ribosomes.
• Ribosomal (rRNA), along with ribosomal proteins, makes up ribosomes, where polypeptides are synthesized.

Stages of Transcription

• Transcription occurs in three stages: initiation, elongation, and termination.

Initiation

• Begins when RNA polymerase attaches to a region of DNA, a promoter.
• A promoter defines the start and direction of transcription, and the strand to be transcribed.

Elongation

• RNA polymerase reads down the DNA template strand in the 3' to 5' direction, and attaches complementary RNA bases.

Termination

Occurs when RNA polymerase comes to a DNA stop sequence.

• The stop sequence causes RNA polymerase to stop transcribing the DNA and to release the mRNA molecule, now called an mRNA transcript.

Processing of RNA Molecules

• Cap on the 5' end: the cap is a modified guanine nucleotide; it helps a ribosome determine where to attach for translation.
• Poly-A tail of 150 to 200 adenines is added on the 3' end, which facilitates mRNA transport out of the nucleus.
• The poly-A tail inhibits mRNA degradation by hydrolytic enzymes.
• In lower eukaryotes, introns are removed via self-splicing, where the intron itself has the capability of enzymatically splicing itself out of a pre-mRNA.
• Spliceosomes, which contain small nuclear RNAs (snRNAs), performs removal in higher eukaryotes.
• A spliceosome uses a ribozyme, an enzyme made of RNA rather than just protein, to cut and remove introns
• Remaining exons are spliced back together produce a mature mRNA transcript.

Translation

• Translation is when the mRNA codon sequence is translated into a protein (amino acid) sequence and occurs at a ribosome.
• Ribosomes have a binding site for mRNA and three binding sites for transfer RNA (tRÑA) molecules.
• The sequence of mRNA codons indicates which amino acids are needed and how they are be linked.
• The tRNA binding sites facilitate complementary base pairing between tRNA anticodons and mRNA codons
• As the mRNA transcript is "read" by the ribosome, the corresponding tRNA molecules bring the amino acids that will be linked to form the protein.
• Translation involves the stages of initiation, elongation, and termination.