Deleterious Genes

Introduction

• A “perfect” population would not carry any deleterious genes—but as we’ve already seen, natural selection does not produce a perfect population.

• Deleterious means damaging—deleterious genes will lead to mild to severely disabling or even fatal conditions at some point in life.

Intro (cont’d)

• We would expect natural selection to remove genes with negative effects from a population.

• Individuals who carry those genes would not have the opportunity to reproduce as much, so the genes should not be passed on.

• And yet we see cases where this expectation is not met..

Why might deleterious genes exist in a population?

• They may be maintained by heterozygote advantage.

• When carrying two copies of a gene is disadvantageous, but carrying only one copy is advantageous, natural selection will not remove the gene from the population—the advantage conferred in its heterozygous state keeps the gene around.

Sickle cell anemia• The gene that causes this

condition is deleterious if you carry two copies of it.

• But if you only carry one copy of it and live in a place where malaria is common, the gene is advantageous because it confers resistance to malaria.

Normal red blood cells (top) and sickle cells (bottom).

• Eg. What is the probability of two heterozygous parents for sickle cell anemia having a child with the sickle cell condition? A child who will be “immune” to malaria? – Phenotypic ratio of 1:4

They may not really reduce fitness.

• Some genetic disorders only exert their effects late in life, after reproduction has taken place.

• For example, the gene that causes Huntington’s disease typically does not exert its devastating effects until after a person’s prime reproductive years.

• Such genes will not be strongly selected against, because an organism’s fitness is determined by the genes it leaves in the next generation and not its life span.

• Often, a fetus with homozygous dominant deleterious genes, such as Huntington’s, will not survive.

They may be maintained by mutation.

• The mutation may keep arising in the population, even as selection weeds it out.

• For example, neurofibromatosis is a genetic disease causing tumors of the nervous system—it is a dominant condition that is inherited from mutations in gametes.

• Natural selection cannot completely eliminate the gene that causes this disease because new mutations arise relatively frequently – in perhaps 1 in 4000 gametes.

• We are unsure of the cause of these spontaneous mutations.

They may be maintained by gene flow.

• The gene may be common, and not deleterious, in a nearby habitat.

• If migration from the nearby population is frequent, we may observe the deleterious gene in the population of interest.

• For example, in places like the U.S., where malaria is not a problem, the gene that causes sickle cell anemia is strictly disadvantageous.

• However, in many parts of the world, the gene that causes sickle cell anemia is more common because a single copy of it confers resistance to malaria.

• This becomes the advantage—thus

keeping the deleterious sickle cell gene at a high level in the population.

Figure 2. Schematic representation of the effect of the sickle cell hemoglobin gene on survival in endemic malarial areas.• People with normal

hemoglobin (left of the diagram) are susceptible to death from malaria.

• People with sickle cell disease (right of the diagram) are susceptible to death from the complications of sickle cell disease.

• People with sickle cell trait, who have one gene for hemoglobin A and one gene for hemoglobin S, have a greater chance of surviving malaria and do not suffer adverse consequences from the hemoglobin S gene.

The sickle-cell trait has spread far and wide, outside the Americas. Regions where the trait is more commonly found (shown in orange stripes) overlap areas where malaria is prevalent (shown in green).

RECESSIVE DELETERIOUS GENE CONDITIONS

• MOST (not all) deleterious genes are recessive traits. Heterozygous people for the trait are carriers but are not afflicted by the condition.

•Alkaptonuria

•Cystic fibrosis

•Duchenne’s muscular dystrophy

•Hemophilia

•Lesch-Nyhan syndrome

•PKU

•Sickle cell anemia

•Tay Sachs

•Adenoleukodystrophy (ALD)

•Alper’s syndrome

•Zellweger’s syndrome

•Aarskog syndrome

DOMINANT DELETERIOUS GENE CONDITIONS

• Some deleterious genes are dominant. Heterozygous people for the trait exhibit the condition. •Brachydactyly•Congenital stationary night blindness•Fascio-scapulo-humeral muscular dystrophy•Huntington’s disease•Pseudo-achondrophastic dwarfism•NF-1 (Neurofibromatosis type 1)•Marfan syndrome•Machado-Joseph disease

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