1. Introduction: Why Harmful Alleles Persist

In the last tutorial, we saw how natural selection, by acting on favorable or unfavorable phenotypes, can shift allele frequencies in populations. It’s reasonable to think that because they produce phenotypes that make individuals less fit, harmful alleles should disappear from any gene pool. But that tends not to be the case. Because harmful alleles are often recessive alleles, they can persist in a population almost indefinitely. And, even harmful dominant alleles, despite selection against the phenotypes they produce, can also often continue to persist in gene pools. Let’s see how this happens.

2. Interactive Reading: Harmful Recessive Alleles

[qwiz qrecord_id=”sciencemusicvideosMeister1961-Pop-gen: Harmful Recessive Alleles IR (AP)”]

[h]Interactive Reading: Harmful Recessive Alleles

[q labels = “top”]

To begin with, why are most harmful alleles recessive? One way to think about this is that recessive alleles are often ___________ versions of a functioning allele. You can see this in the case of Tay-Sachs disease, a lethal disease of the brain. A baby born with Tay-Sachs disease begins life normally. But soon, he or she experiences ongoing deterioration of nerve cells and loss of mental and physical abilities. There’s no cure or treatment.

The allele that causes Tay-Sachs is recessive. If you inherit _____ of these alleles, you’re unable to break down a specific kind of lipid, which builds up in the brain, destroying nerve cells. In other words, the allele codes for a non-functioning _______. The dominant allele codes for a ________ version of the enzyme: if you inherit one version of the functioning allele, you’ll be able to produce the enzyme, and ________ the disease. For more about Tay-Sachs, follow this link to a Wikipedia article (which will open in a new tab)

[l]avoid

[fx] No, that’s not correct. Please try again.

[f*] Correct!

[l]enzyme

[fx] No. Please try again.

[f*] Great!

[l]broken

[fx] No. Please try again.

[f*] Great!

[l]two

[fx] No. Please try again.

[f*] Great!

[l]working

[fx] No, that’s not correct. Please try again.

[f*] Excellent!

[q]In the United States, Tay-Sachs is most common in Jews of Eastern European descent, where it occurs in 1 in every 3500 births. In the larger American population, the frequency is 1 in 320,000 births. Why wouldn’t such a harmful genetic condition simply disappear?

[c*]Show the answer

[f]One reason is that lethal recessive alleles can “hide out” in heterozygotes, who will possess only one copy of the recessive allele. You can prove this to yourself on the next card by working through a Punnett Square.

[q]The allele Tay-Sachs (t) is recessive. We’ll use “T” to represent the allele for the normal enzyme. What will happen if two people who are carriers for the alleles have children?

Step 1: determine the genotypes of the parents

Parent 1) : ___ ___
Parent 2) : ___ ___

Steps 2-4: Complete the Punnett square.

Parent 2
        __             __
Parent 1        __ ___  ___ ___  ___
       __ ___  ___ ___  ___

Step 5: Genotype ratio: ______ TT: ____Tt: ____tt

Step 6: Phenotype ratio: _____ Normal: ____Tay-sachs

[l]T

[fx] No, that’s not correct. Please try again.

[f*] Correct!

[l]t

[fx] No, that’s not correct. Please try again.

[f*] Great!

[l]0%

[fx] No, that’s not correct. Please try again.

[f*] Correct!

[l]25%

[fx] No, that’s not correct. Please try again.

[f*] Excellent!

[l]50%

[fx] No. Please try again.

[f*] Good!

[l]75%

[fx] No, that’s not correct. Please try again.

[f*] Great!

[l]100%

[fx] No. Please try again.

[f*] Great!

[q]Because Tay Sachs is caused by a recessive allele, you can only have the condition if you inherit two copies (tt). Each of your parents would have to be a heterozygote (Tt). With each child they produced, there would be a one in four chance that this child would inherit two recessive alleles and have the tt genotype.

While the loss of ¼ of their offspring from the disease certainly reduces the number of alleles that get passed on, you can see why the allele doesn’t disappear. Half of the children of parents who are heterozygotes will also be heterozygotes (Tt).

In terms of the gene pool, what’s the result of this?

[c*]Show the answer.

[f]The allele persists in the gene pool.

[q]Just to make sure that you’re getting this, identify the genotypes of the individuals in the pedigree on the next page, which shows inheritance of Tay-Sachs disease.

[q labels = “top”]In this pedigree for Tay-Sachs disease, carriers (heterozygotes) are shaded in half way.

 

 

[l]TT

[fx] No, that’s not correct. Please try again.

[f*] Good!

[l]Tt

[fx] No, that’s not correct. Please try again.

[f*] Great!

[l]tt

[fx] No, that’s not correct. Please try again.

[f*] Good!

[/qwiz]

The takeaway message: this harmful allele persists in gene pools because it can hide out in heterozygotes.

3. The persistence of harmful dominant alleles

There are, of course, harmful dominant alleles. We discussed two of these, achondroplasiac dwarfism and Huntington’s disease, in a previous tutorial. Because dominant alleles always have an immediate effect upon the phenotype, they tend to be strongly selected against. However, even harmful dominant alleles can persist in a population’s gene pool. Here’s why.

Let’s look at achondroplasia first. For one thing, while it’s harmful, it’s not lethal. People with achondroplasia not only survive to adulthood: they can also reproduce. When they do, they have a 1 in 2 chance of passing on the allele to the next generation, keeping the allele in the gene pool (achondroplasiacs are never homozygous: two alleles is a fatal combination). In addition, achondroplasia can emerge as a mutation: about 80% of achondroplasiacs are born to parents who are of normal height. If you’re interested, you can read more about achondroplasia at the National Library of Medicine.

The famous American Folksinger Woodie Guthrie was diagnosed with Huntington's disease when he was 40.
The famous American Folksinger Woody Guthrie was diagnosed with Huntington’s disease when he was 40.

Huntington’s disease persists in the population for a different reason. Its key symptoms –including loss of control of movement, difficulty thinking clearly, and depression – don’t set in until middle age. Until recently, when the gene was identified, people only learned that they had Huntington’s after they had already had children (and, in fact, often not until their children were adults). Because of that, possessing the Huntington’s allele never reduced one’s chance of producing offspring, and passing on the Huntington’s allele. And as a result, this allele persists in the population.

4. Checking Understanding

This tutorial focused on why harmful alleles don’t disappear from gene pools.

If you feel that you understand the concepts in this tutorial, take this brief quiz. If not, carefully re-read the material above, and then take the quiz.

Once you’ve mastered all the concepts, you should go on to the next tutorial in the series (link is below).

[qwiz qrecord_id=”sciencemusicvideosMeister1961-Pop-gen: Why Harmful Alleles Persist (AP)”]

[h]Why harmful alleles persist in gene pools

[!!!!!!] question 1 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]True or false: because of natural selection, harmful alleles will inevitably disappear from a gene pool.

[c] True

[c*] False

[f] No. While harmful recessive alleles will be selected against, it’s almost impossible for them to completely disappear from a gene pool. That’s because natural selection can only ‘see’ the phenotype, not the genotype. Recessive alleles can hide out in heterozygotes, allowing them to persist in gene pools. And, as we’ve read above, there are a variety of reasons why harmful dominant alleles can persist in gene pools (including setting in later in life, and not preventing individuals with these alleles from reproducing).

[f] Correct. Because recessive alleles can hide out in heterozygotes, they can persist in gene pools, practically indefinitely. And, as we’ve read above, there are a variety of reasons why harmful dominant alleles can persist in gene pools (including setting in later in life, and not preventing individuals with these alleles from reproducing).

[!!!!!!] question 2 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]Which type of genotype allows for recessive alleles to hide out, shielded from natural selection?

[c] homozygous recessives

[c*] heterozygotes

[c] homozygous dominants

[f] No. Homozygous recessives have two copies of the recessive allele. Whatever phenotype that allele is connected with will be fully exposed to natural selection. Next time, think about which kind of individual could possess a recessive allele, but not express that allele in his or her phenotype.

[f] Correct. In heterozygotes, a recessive allele will be masked by the dominant allele. This allows the recessive allele to hide out in the heterozygote, shielding it from natural selection.

[f] No. Homozygous dominants don’t carry any copies of the recessive allele. Next time, think about which kind of individual could possess a recessive allele, but not express that allele in his or her phenotype.

[!!!!!!] question 3 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]In the Punnett square below, ‘t’ represents the allele for Tay-Sachs disease, and ‘T’ the normal allele. Which square represents the genotype of an individual who is a carrier for Tay-Sachs?

[c] Square 1

[c*] Square 2

[c] Square 4

[f] No. Square 1 shows an individual who has two ‘normal’ alleles. A carrier is someone with a normal phenotype, but who possesses the alele.

[f] Correct. Square 2 shows an individual who is a heterozygote. He or she possesses the allele, but won’t show it in her or his phenotype?

[f] No. Square 4 shows the genotype of an individual who is homozygous recessive. While they certainly carry the allele, they’re not considered a carrier in this special genetics sense of the word. A carrier ‘carries’ the allele, but doesn’t express it in his or her phenotype. Because this individual will express the phenotype, they’re not considered to be a carrier.

[!!!!!!] question 4 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]in the Punnett square below, t represents the allele for Tay-Sachs disease, and T the normal allele. Which square shows the genotype of an individual who would have Tay-Sachs disease?

[c] Square 1

[c] Square 2

[c] Square 3

[c*] Square 4

[f] No. Individual 1 has two ‘normal’ alleles. You’d have to have two recessive alleles in order to express the recessive phenotype, and have the disease.

[f] No. Individual 2 is a heterozygote. He or she possesses the allele, but won’t show it in her or his phenotype. and won’t have the disease.

[f] No. Individual 3 is a heterozygote. He or she possesses the allele, but won’t show it in her or his phenotype. and won’t have the disease.

[f] Yes. Individual 4 is homozygous recessive. He or she has two copies of the recessive allele, and will have Tay-Sachs disease

[!!!!!!] question 5 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]If two individuals who are heterozygous for a lethal (deadly) genetic condition mate and produce offspring, what is the probability that their offspring will inherit the lethal condition?

[c*] one in four

[c] two in four

[c] three in four

[c] four in four

[f] Yes. If you cross two heterozygotes, ‘Tt’ and ‘Tt,’ you can see that one in four of the offspring will inherit the condition.

[f] No. Just examine the Punnett square above. What proportion of the offspring will have the ‘tt’ genotype?

[f] No. Just examine the Punnett square above. What proportion of the offspring will have the ‘tt’ genotype?

[f] No. Just examine the Punnett square above. What proportion of the offspring will have the ‘tt’ genotype?

[!!!!!!] question 6 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]The pedigree chart below shows inheritance of a lethal recessive allele. If B represents the normal allele, and ‘b’ the recessive allele, what would be the genotype of I-1?

[c] BB

[c] bb

[c*] Bb

[f] No. If I-1 had the genotype ‘BB,’ then he could only pass a ‘B’ allele on to his offspring. None of them could have inherited two ‘b’ alleles. Since II-3 has the recessive condition, she has to have inherited two ‘db’ alleles, and therefore her father could not have been ‘BB.’

[f] No. The condition is lethal, which means that you can be born with the condition, but it will kill you before you have the chance to reproduce and pass it on. No adults can be ‘bb.’

[f] Yes. For individual II-3 to have inherited two ‘b’ alleles, she had to have inherited one allele from each of her parents. Both parents had to be carriers, and had to have had a ‘Bb’ gentoype.

[!!!!!!] question 7 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]The pedigree chart below shows inheritance of a lethal recessive allele. If ‘B’ represents the normal allele, and ‘b’ the recessive allele, what would be the genotype of IV-2?

[c] BB

[c*] bb

[c] Bb

[f] No. In a pedigree chart, if the square or circle is colored in, it means that the individual has the condition. An individual with genotype BB will not have the condition, so IV-2 could not be ‘BB.’

[f] Yes. The filled in circle indicates that this girl has the condition. Since the condition is recessive, the only way that you can have it is to be homozygous, making ‘bb’ the only possible genotype.

[f] No. In a pedigree chart, if the square or circle is colored in, it means that the individual has the condition. An individual with genotype Bb is heterozygous for the dominant phenotype, and not have the condition.

[!!!!!!] question 8 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]The pedigree chart below shows inheritance of a lethal recessive allele. Which of the following individuals MUST be a carrier for the lethal allele? (Note that in the feedback for responses, we’ll have ‘B’ represent the normal allele, and ‘b’ the recessive allele)

[c*] I-2

[c] II-4

[c] III-1

[c] IV-2

[f] Yes. I-2 had a child with the condition. In a lethal recessive condition, the parents both have to be carriers, and each has to pass one of their alleles to the offspring who inherits the recessive condition.

[f] No. II-4 COULD be a carrier. But there’s also a 1/4 chance that she is homozygous normal, ‘BB.’ Since she left no offspring, there’s no way to tell if she is ‘BB’ or ‘Bb.’

[f] No. As one of the offspring of II-2, who might be a carrier, III-1 or any of her siblings might carriers. And, in fact, III-3 is definitely a carrier, because he’s the parent of a child with the condition. But both III-1 and III-2 could be homozygous dominant (BB) or heterozygotes (Bb). Without knowing their offspring, there’s no way to tell.

[f] No. IV-2 has the condition. They have the disease, and will die (or already died) from it, because it’s lethal in homozygotes. Only heterozygotes are considered to be carriers.

[!!!!!!] question 9 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]The pedigree chart below shows inheritance of a lethal recessive allele.Which of the following individuals inherited two copies of the lethal allele? (Note that in the feedback for responses, we’ll have ‘B’ represent the normal allele, and ‘b’ the recessive allele)

[c] I-2

[c] II-4

[c] III-3

[c*] IV-2

[f] No. In a pedigree chart, individuals who have filled-in circles or squares have the condition. If the individual’s square or circle is not filled in, they don’t have the condition. Also, in this case, because the condition is lethal, no parents will have it. I-2 is definitely a heterozygote (because she’s the mother of a child born with the condition) but she doesn’t have the condition.

[f] No. In a pedigree chart, individuals who have filled-in circles or squares have the condition. If the individual’s square or circle is not filled in, they don’t have the condition. Also, in this case, because the condition is lethal, no parents will have it. I-2 is definitely a heterozygote, which means that she has only one copy of the allele.

[f] No. In a pedigree chart, individuals who have filled-in circles or squares have the condition. If the individual’s square or circle is not filled in, they don’t have the condition. Also, in this case, because the condition is lethal, no parents will have it. III-3 is definitely a heterozygote (because he’s the father of a child born with the condition) but he doesn’t have the condition.

[f] Yes. Just by the fact that her circle is filled in, you know that IV-2 has the condition. Because the condition is lethal, she had to have inherited two copies of it. Her genotype would be ‘bb.’

[!!!!!!] question 10 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]Achondroplasia, a genetic form of dwarfism, is caused by a dominant allele. Which of the following is NOT a reason why achondroplasia has stayed in the gene pool? In other words, from the list below, find the FALSE statement.

[c] Occasionally, normal alleles mutate into the achondroplasia allele.

[c] Achondroplasiacs have some health problems, but they can become adults who have children of their own.

[c*] Dominant alleles, because they’re dominant, tend to increase in frequency over time.

[f] No. Remember that you’re looking for a false statement. This one’s true. While achondroplasia is uncommon, among achondroplasiacs it’s not uncommon for two normal sized parents to have a child with achonrdroplasia. The new allele is a mutation.

[f] No. Remember that you’re looking for a false statement. It is true that achondroplasiacs can have children. When they do, there’s a 1 in 2 chance that they’ll pass on their achondroplasia allele (achondroplasiacs are never homozygous dominants: that combination is lethal).

[f] Excellent. You’ve found the false statement. Dominant alleles are only dominant because when they’re paired with a recessive allele, the dominant allele determines the phenotype. On a population level, they show no tendency to grow or spread.

[!!!!!!] question 11 +++++++++[/!!!!!!]

[q topic= “why_harmful_alleles_persist”]Huntington’s disease is caused by a dominant allele. Why does it persist in the gene pool?

[c] Because dominant alleles, since they’re dominant, tend to increase in frequency over time.

[c*] Huntington’s disease sets in later in life.

[f] No. This is a major misconception in population genetics, and you should re-read the misconception alert earlier in this tutorial series. Dominant alleles are only dominant when they’re paired with a recessive allele. In that situation, the dominant allele determines the phenotype. On a population level, they show no tendency to grow or spread.

[f] Exactly. Huntington’s disease sets in late in life. Throughout history (especially when life spans were shorter than they are today and there was less knowledge of genetics), people with Huntington’s reproduced before they knew they had the disease, or understood that they could pass it on to their offspring.

[x]

[restart]

[/qwiz]

Links