Population genetics

Population genetics is the study of genetic variation within the population, that involves the examination and exhibits certain changes in the frequency of the gene and allele occurring in the population over a certain time and space. Many genes in the population occur in several varied forms, referred to as alleles are known as polymorphic. If the change occurs at a single position in the DNA sequence making it abnormal and rarer in the population, it is referred to as mutation and if the change occurring in the DNA population is common in the population, then it is referred to as polymorphism. As this polymorphism occurs at a single nucleotide, so it is known as Single Nucleotide Polymorphism (SNP). The variation can only be then reported as SNP if less than 1% of the population acquires a similar nucleotide change in the sequence of the DNA (Www2.le.ac.uk, 2019). For example- there are per se two individuals who are deaf. The genes contributing to deafness are present in both but there are differences in the locations of their alleles making one deaf and other being able to listen. Therefore, the presence of the genes doesn't leave the person diseases, the differences in the SNPs contribute a lot to the manifestation of the disease/condition. Population genomics has brought various advancements in the fields of evolution, ecology, genomic medicines, breeding of plants and animals, conversational genetics, and pharmacology. Population genomics has revolutionized the understanding of the various evolutionary processes such as mutation, genetic drift, gene flow, natural selection, and non-random mating. These processes not only helps in bringing about change at the loci level producing interindividual differences across the genome and population but also helps in the refinement in the assessment  of certain genetic structures such as size of the population, flow of genes, differences at the genetic level, demographics, establishing phylogenetic relationships between the extant and the extinct species. Thus, the study helps in determining certain genes and genetic variants that are commonly present in the population and these changes further helps in the designing of drugs also known as personalized drugs. Personalized drugs are the drugs which are designed according to the genotype of a certain population or the individual (Rajora, 2019). The collection of the number of alleles present among the total number of genes, that were found to be present in the inter-breeding population is known as gene pool. Every member of the population gets a set of certain alleles from another group (parents) which passes it to another group (children) present in the population leading to variations in the population. The study of these variations that arise due to the transmission of a certain set of alleles and genes, from one generation to the another, is called population genetics (Www2.le.ac.uk, 2019). An example illustrating the variations is, the differences present among the humans concerning their heights. This characteristic is influenced not by a particular gene but by a particular set of genes despite having a little effect. It's a general observation that height is the average of the heights their parents have. But according to the population geneticist, the height is a characteristic that is determined by the population meaning it is highly influenced by the environment rather than only the genetic component. Thus, the height of an individual is determined according to the average height of the population. This is to so to maintain a bell-shaped curve as per the Hardy- Weinberg equilibrium. Hardy-Weinberg Equilibrium states that the allelic and the genotypic frequencies would remain constant from generation to generation in the absence of other evolutionary processes i.e., the sum of the square of two alleles per se, p and q must be equal to 1 ( p2 + 2pq + q2 = 1), assuming a huge population not having any –

  • mutation;
  • selection;
  • genetic drift;
  • migration;
  • non-random mating

This theory was given was way back in the early 220th century by Hardy and Weinberg in 1908. Today also, it is checked if the genotypes satisfy Hardy-Weinberg's theory. Deviations from the theory would tell us about the improper genotypes or the structure of a population is appropriate or there is the dissociation of the marker with the disease (Wigginton, Cutler and Abecasis, 2005). Mutation serves as the prime factor in the introduction of the novel alleles in the genome whereas, other factors thus contribute to increasing or reducing the presence of the alleles. Genetic drift results in intensifying the arbitrary fluctuations when they get transferred from one generation to the generation, thus, leading to either bottleneck effect or the founder effect. It can also lead to a decrease in the variations thus leading to an increase in divergence among the population. The divergence results in bringing up so many differences between the genotypes of the population that they can no longer interbreed, hence, it leads to the formation of new species leading to specialization. The phenomenon of natural selection is in fact steering i.e., the presence of healthy allele contributes to offer a selective advantage, whereas, the presence of non-healthy allele offers to contribute to increasing genetic load. The mutation that generally decreases the quality of life generally gets eliminated from the population by the passage of time. On the other hand, the beneficial one remains in the genome. This scenario is called a balanced polymorphism where heterozygotes pose a selective advantage for a specific allele. For example- sickle cell anemia is a condition in which the gene responsible for the production of hemoglobin gets mutated. A person with two copies of HbS will manifest the condition, whereas, the person with one normal copy and one diseased (HbA/HbS) will have certain symptoms of the disease but wouldn't manifest the condition. The presence of heterozygosity confers a selective advantage, as these people are more resistant to malaria than a person with normal copies of the allele (HbA/HbA). Natural selection and assertive mating bring up changes in the frequency of the genes. The changing frequencies result in an increase or decrease in the reproductive success rates between individuals. Migration leads to the introduction of new alleles to the gene pool, disturbing the genotypic component of the population (Www2.le.ac.uk, 2019).

Genome-Wide Association Studies (GWAS) also known as Wide Genome Analysis (WGA) was a study planned to observe variations in the genome upon the aspect of inter-individual differences.  This is related to the study of genomic variants i.e. SNPs present in the population. The first study that was carried out by GWAS was on height. The study couldn't be able to predict many variations because of two reasons. One is a low sample size and the other is, the study related to the twins showed that the heritability was a major contributing factor. The problem was then identified, that these results lacked statistical power and couldn't be able to spot polymorphisms and but with a larger number of samples the study was able to prove that the character is dependent upon several loci present. The one method by which the non-mappable components of the genome could be statistically measured is known as polygenic scores. This is the method signifies the shift from the identification of phenotype to genotype by having an estimation of the sum of scores that contribute towards many SNPs that may not be statistically significant. The correct estimation of the polygenic scores could only be made possible when the effects in a non-structured population are difficult to estimate, even if, the environmental differences get uncontrollable. To consider this fact, an example of chopstick eating skills was considered. This skill was purely genetic related. Variations can still be observed when the environmental differences could be considered as cultural background too plays a big role in the manifestation of a trait. When GWAS was carried out then it was seen that it was unable to find any of the variants that could be labelled as chopstick eating skill SNP but only showed the difference in the frequency of East Asia and the other world. The fact that if genetics or selection, which one has been responsible for the differences seen in height among the population is still unclear. However, genetics do play a significant role in bringing up differences concerning the height, and this has now been cleared real by GWAS. The main problem is that it is unclear how to control the structurally complexed population and environmental heterogeneity. Biases present in the distinct loci may be tiny but when observed among the thousands of loci significant differences would be obtained - as was done in doing polygenic scores. To control bias, standard methods such as ‘principal component analysis' was carried out during simulations but when it was confronted with the real data it proved to be insufficient. However, quantitative genetics has been proved to be sufficiently successful because of the larger sample size; controllable environment and short predictions. When it is applied to the natural population is thus unsuccessful because of the non-homogeneous environment (Barton et. al., 2019).

In a nutshell, it can be said that the decrease in genetic variability, can be due to allelic loss, polymorphisms or varied genotypes, etc. The events such as migration or recolonization or consanguineous marriages or decreased diversity due to bottleneck effects can steadily become a reason for the diminution of genetic variability. At last, these losses get fixed in the population generating substantial differences which are then favoured by topographical isolation and inadequate gene flow. Due to these exemptions of the Hardy-Weinberg Equilibrium that are imprinted in the genetic backbone of the population, it became possible to recreate the evolutionary history of man (Octavio-Aguilar and Ramos-Frías, 2019).

References

Barton, N., Hermis, J. & Nordborg, M., Mar 21, 2019. Population Genetics: Why structure matters. eLIFE, Volume e45380.

Rajora, O. (2019). Population Genomics. Switzerland AG: Springer Nature.

Wigginton, J., Cutler, D., and Abecasis, G. (2005). A Note on Exact Tests of Hardy-Weinberg Equilibrium. American Journal of Human Genetics, [online] 76(5), pp.887-893. Available at: https://www.sciencedirect.com/science/article/pii/S0002929707607356.

Www2.le.ac.uk. (2019). Population genetics — University of Leicester. [online] Available at: https://www2.le.ac.uk/projects/vgec/highereducation/topics/population-genetics [Accessed 22 Jul. 2019].

Octavio-Aguilar, P. and Ramos-Frías, J. (2019). Aplicación de la genética de poblaciones en el ámbito de la medicina. [online] Available at: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-41572014000200004&lng=en&nrm=iso&tlng=en.