Genetic diversity and meiosis II – PART II

- Genetic diversity - Population genetics  Genetic Variation Is a well-adapted population highly homozygous for most favorable alleles?  turns out that most populations, even the well adapted ones, have a high degree of heterozygosity across their genomes. How was this realized?  the gene for the alcohol dehydrogenase in drosophila, different genes from different subpopulations (1,2,3,4,5) the most common ones were isolated and sequenced and was realized that there are lots of differences in the genetic code. This would by definition show the allelic differences, most of them are silenced and don’t change their aminoacidic sequence; some are introns so they don’t affect the protein, and some (the one with the star) gives two different proteins (the ones that we know beforehand). We can have neutral mutations of different kind; the one that is easy to understand if there is not chance in a coded aminoacind, never the less the dna sequenced is changed and maybe a prerequisite for a secondary mutation to then change the aminoacid or the neutral mutations where a different aminoacid is encoded but there is not phenotypic difference in a given environment. Let’s imagine that yeast contains exactly the same aminoacids encoded by different genes, in terms of the difference sequence; so you could create two yeast strains where all the 6000 proteins are encoded by a different dna code, because of the degenerated code. We would have two different organisms that if we analyze the proteins they would be authentycal, but they could not interbreed because during miosis they need to exchange genetic material and they can’t. So mutation even though they might be neutral and not lead to any change in the aminoacid code or they may not change the expression of a proteins, during meiosis the dna sequences have to pair and the divergency must not be too big.  so you would create a yeast that is identical on the protein level but not on the dna level and whey would not interbreed, because of problems in miosis. Even though there are neutral mutations, they might not be neutral in terms of the success within a population b ecause they still need to find a friend during miosis and the chromosomes still need to pair. Arabidobsis thaliana was sequenced too; in the 1000 genome project realized that there are millions of single nucleotides polymorphisms, millions of insertions and deletions, and thousands of structural variants. Across the population of humans were found millions of genetics aberrations.  so we know that there is genetic diversity  Chromosome aberrations include changes in chromosome number (gains and losses) and changes in structure (deletions, inversions, and exchanges). In CFTR – cystic fibrosis transmembrane conductance regulator gene; in cystic fibrosis there are a lot of mutations known, yet one of them in the exon10 at position 508 a Phenilalanine deletion is responsible for about 2/3 in all mutants alleles in all Europe. In this gene there are many mutations known, and these are the disease pairing mutations, but there are many more; this is not reflecting ther true g3netic diversity but that showing genetic diversity leading to a disease. There is lot of genetic diversity in all populations, even in the stable ones. Why is there so much genetic variations? Mutations that are favorable or detrimental are preserved or removed from the population, respectively, by natural selection.  so there is a fitness advantage of disadvantage and so the allele frequency in the population will change. Yet, the frequency of the neutral alleles in a population will be determined by mutation rates and random genetic drift, not by selection. The diversity of alleles at most loci does not , therefor, reflect the action of natural selection, but instead is a function of population size (larger populations have more variation) and the fraction of mutations that are neutral.   Part of the explanation for the surprising density of genetic variation is that there is actually natural selection ongoing; there is the example of enzymes with variants, such as the sickle cell anemia. - If you have the normal protein then you are susceptible to malaria, but you have no sickle cell anemia. - If you’re heterozygote, you’re resistant to malaria and have inly mild sickle cell anemia. - If you’re homozygote carrier than you have a very fatal disease that is not beneficial. Resistant to malaria, but has fatal sickle cell disease. If you have two alleles of a certain gene, then you can have three genotypes. Key elements of population genetics depend on the calculation of allele frequencies and genotype frequencies in a gene pool, and the determination of how these frequencies change from one generation to the next. How do these frequencies change from one generation to the next? Hardy-Weinberg found a model to describe what happens in an ideal population. There are genes that may differ in their allelic nature and as an individual you can have a certain combination of those, and this combination gives you a genotype. Now we focus on the population wide frequency of the alleles and the population wide frequency of their possible genotypes. Are two connected different things: - Relative proportions of alleles (in the gene pool) - Frequencies of genotypes (different ones in the population) A model for population analysis has been conceived to analyze the relationships between the proportions of alleles in the gene pool and the frequencies of their current genotype, but it’s only valid under certain completely hypothetical pre-assumptions: population is infinitively large, it is not subject to any evolutionary forces such as mutation, migration or selection. The Hardy-Weinberg Law A and a allele frequency is 0.7 and 0.3; their sum is one and this means that all the alleles of a gene A present in the population are accounted for. Now we can think about how this alleles relate from alleles frequencies to genotype frequencies; we can plot something like this: possible sperm (generative post meiotic cells), it can be any generative cell or any organism with any given ploidy; the two alleles, the sperm, we get one chromosome (number 5) where this gen is situated; this gene can be A or a; we know their proportions (0.7 and 0.3) and the likelihood that a sperm cell receives A or a is exactly related to the alleles frequencies on the population. What genotype is the new organism? It will be according to the sperm and egg cell frequencies of the given alleles; so we have to multiple these probabilities to give the combine probabilities that those alleles and up in the same organism.