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N a m e : A v a n i Rathod G r p. N o. : 1 9 5 - B T o p i c : G e n e t i c L

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Genetic load Genetic load: the extent to which the fitness of an individual is below the optimum for the population as a whole due to the deleterious alleles that the individual

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Слайд 1Name: Avani Rathod Grp. No.: 195-B Topic : Genetic Load In Human

population

Name: Avani Rathod Grp. No.: 195-B Topic : Genetic Load In Human population

Слайд 2Genetic load
Genetic load: the extent to which the fitness

of an individual is below the optimum for the population

as a whole due to the deleterious alleles that the individual carries in its genome.
Genetic load : The average number of lethal mutations per individual in a population. Such mutations result in the premature death of the organisms carrying them.
Genetic load Genetic load: the extent to which the fitness of an individual is below the optimum

Слайд 3Genetic load: the difference between the average fitness of the

population and the fitness of the best genotype. It measures

the probability of selective death of an individual in a population.
W = average fitness
Genetic load (L) = 1 - W
Genetic load: the difference between the average fitness of the population and the fitness of the best

Слайд 4Types of Genetic Load
Three main kinds of genetic load may

be recognized:
A.Input Load: in which inferior alleles are introduced into

the gene pool of a population either by mutation or immigration;
B. Balanced Load: which is created by selection favouring allelic or genetic combinations that, by segregation and recombination, form inferior genotypes every generation; and

Types of Genetic LoadThree main kinds of genetic load may be recognized:A.Input Load: in which inferior alleles

Слайд 5C. Substitutional Load: Which is generated by selection favouring the

replacement of an existing allele by a new allele.
Originally called

the ‘cost of natural selection’ by the geneticist J. B. S. Haldane, substitutional load is the genetic load associated with transient polymorphism.
The term ‘genetic load’ was originally coined by H. J. Muller in 1950
C. Substitutional Load: Which is generated by selection favouring the replacement of an existing allele by a

Слайд 7Genetic load an Example… Selective death (or genetic death): the chance

that an individual will die without reproducing as a consequence

of natural selection. [e.g.,15% of offspring in above]
Genetic load an Example…  Selective death (or genetic death): the chance that an individual will die

Слайд 8Causes of Genetic Load
1.Deleterious mutation
2.Beneficial mutation
3.Inbreeding
4.Recombination/segregation load

Causes of Genetic Load1.Deleterious mutation2.Beneficial mutation3.Inbreeding4.Recombination/segregation load

Слайд 9DELETERIOUS MUTATIONS
Deleterious mutation load is the main contributing factor to

genetic load overall.
Most mutations are neutral or slightly deleterious,

and occur at a constant rate.
The Haldane-Muller theorem of mutation–selection balance says that the load depends only on the deleterious mutation rate and not on the selection coefficient.
Specifically, relative to an ideal genotype of fitness 1, the mean population fitness is exp(-U) where U is the total deleterious mutation rate summed over many independent sites.
DELETERIOUS MUTATIONSDeleterious mutation load is the main contributing factor to genetic load overall. Most mutations are neutral

Слайд 10High load can lead to a small population size, which

in turn increases the accumulation of mutation load, culminating in

extinction via mutational meltdown.
The accumulation of deleterious mutations in humans has been of concern to many geneticists, including Hermann Joseph Muller, James F. Crow, Alexey Kondrashov,W. D. Hamilton,and Michael Lynch.
High load can lead to a small population size, which in turn increases the accumulation of mutation

Слайд 11Beneficial mutation
New beneficial mutations create fitter genotypes than those previously

present in the population.
When load is calculated as the difference

between the fittest genotype present and the average, this creates a substitutional load.
The difference between the theoretical maximum (which may not actually be present) and the average is known as the "lag load.

Beneficial mutation	 New beneficial mutations create fitter genotypes than those previously present in the population.When load is

Слайд 12Motoo Kimura's original argument for the neutral theory of molecular

evolution was that if most differences between species were adaptive,

this would exceed the speed limit to adaptation set by the substitutional load.
However, Kimura's argument confused the lag load with the substitutional load, using the former when it is the latter that in fact sets the maximal rate of evolution by natural selection.
More recent "travelling wave" models of rapid adaptation derive a term called the "lead" that is equivalent to the substitutional load, and find that it is a critical determinant of the rate of adaptive evolution.
Motoo Kimura's original argument for the neutral theory of molecular evolution was that if most differences between

Слайд 14Inbreeding
Inbreeding increases homozygosity.
In the short run, an increase in

inbreeding increases the probability with which offspring get two copies

of a recessive deleterious alleles, lowering fitnesses via inbreeding depression.
In a species that habitually inbreeds, e.g. through self-fertilization, recessive deleterious alleles are purged.
InbreedingInbreeding increases homozygosity. In the short run, an increase in inbreeding increases the probability with which offspring

Слайд 15Recombination/segregation load
Combinations of alleles that have evolved to work well

together may not work when recombined with a different suite

of coevolved alleles, leading to outbreeding depression.
Segregation load is the presence of underdominant heterozygotes (i.e. heterozygotes that are less fit than either homozygote).
Recombination/segregation loadCombinations of alleles that have evolved to work well together may not work when recombined with

Слайд 16Recombination load arises through unfavorable combinations across multiple loci that

appear when favorable linkage disequilibria are broken down.

Recombination load can

also arise by combining deleterious alleles subject to synergistic epistasis, i.e. whose damage in combination is greater than that predicted from considering them in isolation.
Recombination load arises through unfavorable combinations across multiple loci that appear when favorable linkage disequilibria are broken

Слайд 17Genetic load : Mutation

Genetic load : Mutation

Слайд 18Genetic load: segregational
Segregational load is a big problem for the

balance school:

Well known examples exist; Haemoglobin, MHC locus, etc.

Genetic load: segregational Segregational load is a big problem for the balance school:Well known examples exist; Haemoglobin,

Слайд 19Balance school would extend this to most polymorphic loci in

the genome. Let’s see if this will work

Humans:
30% of loci

are polymorphic (from Harris 1966)
30,000 genes (from recent genome projects), so 9000 are polymorphic
Let’s assume a very small load on average: L = 0.001
Let’s assume that only half are under balancing selection (4500) [remember the balance school predicted a majority would be under balancing selection]
Fitness of an individual locus = 0.999
Fitness over whole genome = 0.9994500 = 0.011
Load = 1- 0.011 = 0.989 [That is huge!!!]
Cost = 0.989/0.011 = 89
Balance school would extend this to most polymorphic loci in the genome. Let’s see if this will

Слайд 20There is a cost to selection, in genetic death, during

this time period

There is a cost to selection, in genetic death, during this time period

Слайд 21 Migration load
Migration load is the result of nonnative organisms that

aren’t adapted to a particular environment coming into that environment.


If they breed with individuals who are adapted to that environment, their offspring will not be as fit as they would have been if both of their parents had been adapted to that particular environment.
Migration loadMigration load is the result of nonnative organisms that aren’t adapted to a particular environment coming

Слайд 22“It is altogether unlikely that two genes would have identical

selective values under all the conditions under which they may

coexist in a population. … cases of neutral polymorphism do not exist … it appears probable that random fixation is of negligible evolutionary importance”
-------Ernst Mayr
“It is altogether unlikely that two genes would have identical selective values under all the conditions under

Слайд 23Neo-Darwinism
1930’s:
⎯ no way to test the predictions of different

schools. ⎯arguments centered on mathematical models


1950’s and 1960’s:

⎯ protein sequencing (slow and painful)
⎯ protein gel electrophoresis (fast and cheap
Neo-Darwinism 1930’s: ⎯ no way to test the predictions of different schools.   ⎯arguments centered on

Слайд 24Defining Directional Section
Directional selection: selection that favours the phenotype at

an extreme of the range of phenotypes


Directional selection: can be

subdivided into two broad categories.
1.Positive Darwinian selection
2.Negative Darwinian selection

Defining Directional SectionDirectional selection: selection that favours the phenotype at an extreme of the range of phenotypesDirectional

Слайд 25Defining two types directional selection

Type 1:

Positive Darwinian selection: directional selection for fixation of a new and beneficial mutation in a population.


Defining two types directional selection

Слайд 26Positive selection: Same as above. [Note that the above term

is also shortened to “Darwinian selection”.

Positive selection: Same as above. [Note that the above term is also shortened to “Darwinian selection”.

Слайд 27

Type 2:

Negative Darwinian selection: directional selection for removal of a new and deleterious mutation from a population.

Negative selection: same as “negative Darwinian selection”.

Purifying election: same as negative selection.

Слайд 29THANK YOU

THANK YOU

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