3.1 Genes

*Describe an example of a gene with multiple alleles.* Understanding: The various specific forms of a gene are alleles.

Nearly all genes have multiple alleles (multiple versions). For example, in humans the ABO blood type is controlled by a single gene, the *isoagglutinogen gene* (I for short). The I gene has three common alleles: I^A: codes for antigen type A I^B: codes for antigen type B i: codes for no antigen

*State the source of new alleles of a gene.* Understanding: New alleles are formed by mutation.

New alleles (versions) of a gene are formed through random *mutation* (changes) in the DNA sequence of the gene. Most new mutations arise due to errors in DNA replication.

*State the number of genes in the human genome.* Application: Comparison of the number of genes in humans with other species.

There are an estimated *20,000-25,000 genes* in the human genome.

*Define "sequence" in relation to genes and/or genomes.* Understanding: The entire base sequence of human genes was sequenced in the Human Genome Project.

*Sequence (noun)*: the order of the nitrogenous bases in a gene or genome. "The sequence of the gene is ATCCGTA." *Sequence (verb)*: the process of determining the order of the nitrogenous bases in a gene of genome. "We are going to sequence the gene to test for a genetic disease."

*Define "gene".​* Understanding: A gene is a heritable factor that consists of a length of DNA and influences a specific characteristic.

A gene is a *sequence of DNA nucleotides that codes for an RNA or protein* that in turn influences a trait/characteristic.

*Define "gene locus."* Understanding: A gene occupies a specific position on a chromosome.

A gene locus is the *location of a gene on a chromosome.* Each chromosome carries many genes.

*Define "allele."* Understanding: The various specific forms of a gene are alleles.

An *allele is a version/variation of a gene.* Most genes come in a variety of different forms. For analogy: if there is an ice cream gene , then the alleles would be vanilla, chocolate and mint.

*Outline the use of a computer software tool to create an alignment of the gene sequences between different species.* Skill: Use of a database to determine differences in the base sequence of a gene in two species.

A sequence alignment is a way of *arranging DNA sequences so that similarities and differences between the sequences of different species can be identified*. Computer software programs are able to complete alignments *quickly and accurately*.

*Define "substitution mutation."* Application: The causes of sickle cell anemia, including a base substitution mutation, a change to the base sequence of mRNA transcribed from it and a change to the sequence of a polypeptide in hemoglobin.

A substitution is *a mutation that exchanges one base for another* (i.e., switching an A to a C). Such a substitution could: change a codon to one that encodes a different amino acid and cause a change in the protein produced.

*State similarities between alleles of the same gene.​* Understanding: The various specific forms of a gene are alleles.

Alleles of the same gene are *found at the same locus on homologous chromosomes,* *have mostly the same nucleotide sequence* and *code for the same general type of protein* (for examples the A and B alleles for blood type both code for a membrane embedded protein).

*State the difference between alleles of the same gene.​* Understanding: Alleles differ from each other by one or only a few bases.

Alleles of the same gene are *slightly different from each other in the sequence of nucleotides.* They can vary by just one base (i.e. A -->T), called a single nucleotide polymorphism (SNP) or by the insertion or deletion of a base.

*Explain which gene types are often used to assess the differences in the base sequences of a gene between two species.* Skill: Use of a database to determine differences in the base sequence of a gene in two species.

Genes that are *present in the species being studied* must be selected. For example, the COX1 gene (which codes for a protein involved in cellular respiration) is present in the majority of eukaryotic species so it is a good choice for comparing sequences between species. Additionally, the gene has been sequenced for many species and is therefor *accessible in genome databases*.

*Describe the relationship between the number of genes in a species and the species complexity in structure, physiology and/or behavior.*​ Application: Comparison of the number of genes in humans with other species.

In general, *eukaryotes have more genes than prokaryotes*. However, within plants and animals there is *little correlation between complexity and the number of genes*.

*Summarize the information that can be determined given gene sequence alignment data.* Skill: Use of a database to determine differences in the base sequence of a gene in two species.

Sequence alignment data can be used to *measure evolutionary relationships between species*. The more similar two sequences, the more closely related two species are.

*Define "sickle cell anemia."* Application: The causes of sickle cell anemia, including a base substitution mutation, a change to the base sequence of mRNA transcribed from it and a change to the sequence of a polypeptide in hemoglobin.

Sickle cell anemia is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules, which distort red blood cells into a sickle, or crescent, shape.

*State the cause of sickle cell anemia, including the name of differences in the Hb alleles.* Application: The causes of sickle cell anemia, including a base substitution mutation, a change to the base sequence of mRNA transcribed from it and a change to the sequence of a polypeptide in hemoglobin.

Sickle cell anemia is caused by *single base substitution mutation* in the gene coding for one of the polypeptide chains in hemoglobin. In the mutation, the sequence *GAG (on the sense strand of DNA) is mutated to GTG*. This *results in a codon that codes for the amino acid VAL instead of GLU*.

*Outline the consequences of the sickle cell mutation on the impacted individual.* Application: The causes of sickle cell anemia, including a base substitution mutation, a change to the base sequence of mRNA transcribed from it and a change to the sequence of a polypeptide in hemoglobin.

Sickle cells are destroyed rapidly in the bodies of people with the disease, causing anemia, a condition in which there aren't enough healthy red blood cells to carry adequate oxygen to the body's tissues. Anemia results in fatigue and weakness. The sickle cells also block the flow of blood through vessels, resulting in lung tissue damage that causes acute chest syndrome, pain episodes and stroke. It also causes damage to the spleen, kidneys and liver.

*Describe a base substitution mutation.* Understanding: New alleles are formed by mutation.

Substitution mutations *replace one base with another.* The new allele that results from the mutation might result in: *Missense* - cause one amino acid in the protein coded for by the gene to change *Silent* - have no effect on the protein coded for by the gene *Nonsense* - code for an incomplete, non-functioning polypeptide for form.

*Outline outcomes of the Human Genome Project.​* Understanding: The entire base sequence of human genes was sequenced in the Human Genome Project.

The Human Genome Project: -determined the sequence of the base pairs in the sample humans - identified the location of many genes on chromosomes - identified human genetic variations (SNPs) -improved detection of genetic diseases -developed new technologies, medical treatments and research techniques -spurred international collaboration

*Define "genome."* Understanding: The genome is the whole of the genetic information of an organism.

The genome is the *complete set of genes and genetic material present in a cell or organism.*

*State the size in base pairs of the human genome.* Understanding: The genome is the whole of the genetic information of an organism.

The human genome is composed of about *3.2 billion base pairs* divided amongst nucleus chromosomes and mitochondrial DNA.

*Outline the technological improvement that sped the DNA sequencing process.* Nature of Science: Developments in scientific research follow improvements in technology-gene sequencers are used for the sequencing of genes.

The largest advancement in gene sequencing was the automation of the process with computer-assisted technology. What used to take humans hours or days can now be done by a computer much *more rapidly, more accurately and for less money.*

*State the aim of the Human Genome Project.* Understanding: The entire base sequence of human genes was sequenced in the Human Genome Project.

The main aims of the Human Genome Project were to determine the sequence of the ≈ 3.2 billion base pairs and identify the location of the ≈ 20-25 thousand genes in the human genome.

*Explain the consequence of the mutation causing sickle-cell anemia in relation to the processes of transcription and translation.* Application: The causes of sickle cell anemia, including a base substitution mutation, a change to the base sequence of mRNA transcribed from it and a change to the sequence of a polypeptide in hemoglobin.

With sickle cell, the sequence GAG (on the sense strand of DNA) is mutated to GTG. When the mutated sickle cell gene is transcribed, the mRNA codon becomes GUG rather than GAG. During translation, the mutated codon will code for the wrong amino acid to join the polypeptide (where there should be a glutamic acid a valine is inserted instead). As a result, the polypeptide will fold into an incorrect shape, resulting in a distorted hemoglobin molecule that in turn alters the red blood cell shape and reduces its ability to carry oxygen.