3 Relevance of Human Population Genetics in Anthropology

Dr. Vani Kandpal

Introduction

Before defining human population genetics, it’s of prime importance to define population in this context. A population constitutes member of a species interbreeding among them and inhabiting a well defined geographical limits. Human population genetics deals with the distribution of genes and genotype frequency in a population, and predicting the ways they would change over a period of time. Alleles are two or more alternative forms of gene that arise by mutation. Though a gene can have different alleles but it is classed as a polymorphic when the least common allele must have a frequency of 1 per cent or more in the population. Polymorphism literally means many forms of a character which is naturally occurring. When the environment changes, new solutions to new problems are needed, this creates possibility that some previously deleterious allele’s mutant alleles may become beneficial. Even if environment doesn’t change, a random genetic change may occur that is advantageous. During initial years of selection for a new mutation most individuals will be heterozygotes. Only when the frequency of mutant allele has increased enough that there will be reasonable matings between heterozygotes will homozygous progeny be produced. This mutant allele will be exposed to selection in homozygous state. If homozygous individuals (mutant allele) are found to be more fit than heterozygotes, selection will go completion and normal allele will be replaced by new allele. However, if it remains advantageous in heterozygous state, selection will slow down as the frequency of mutant allele increases and eventually equilibrium is maintained in which new and normal allele are both present. This type of polymorphism is called balanced polymorphism. A polymorphism is a condition where the two alleles are not rare. Most of the polymorphism found in human populations fall into two main categories: blood cell antigens and blood proteins. The first class of polymorphisms detected by immunological techniques is that of blood group, the ABO blood groups. The ABO blood group is important for medical practise. The Rh system has also become well known due to haemolytic disorder of new born. Some blood group and other polymorphisms detected by immunological techniques are potentially subject to a special type of selection called incompatibility. One of the oldest known polymorphism is that for capacity to taste phenylthiocarbamide (PTC). For some people it has faint taste or no taste while others find its taste bitter. Polymorphism reflects variability among the human population.

In would not be less worth mentioning here that Human Population Genetics and Anthropology are closely knit subjects. Anthropology is a discipline which studies human beings within time and space. The two major branches of anthropology are physical/ biological and social / cultural anthropology. The Physical anthropology deals with evolution and the variability present among human beings. Human population genetics deals with the Mendel’s laws and other genetic principles. It is part of evolutionary genetics which understands species evolution and population divergence. Evolution is best described as change in the gene frequencies. The individual is not significant unit in evolution as its genetic constitution doesn’t change during its life. While a population has continuity from generation to generation, its genetic constitution may change –evolve-over the generations. This makes population the unit of study. Diversity plays a key role in evolution. Phenotypic diversity is caused by genetic diversity. The, variability at genetic level is dealt with the subject of human population genetics. This variability is result of population history which is recorded n DNA sequences and their correct interpretation leads to understanding of secret of past evolution and history. The science of population genetics is an integral component of biological anthropology in understanding human evolution and in pursuing the goal of human origins vis-à-vis the divergence of human groups. Population genetics provides underpinning for all evolutionary biology. The word evolution includes all changes, large or small, visible and invisible, adaptive and non-adaptive. In this context, the existence of genetic polymorphisms in human populations becomes immensely important in seeking answers to our understanding of the evolutionary significance of these variations. Stated simply, population genetics is the study of genetic variation through gene and genotype frequencies in a population, and predicting the way they would change or would be maintained over a period under the differential effects of various micro-evolutionary forces. The important concepts of human population genetics which play an important role in understanding the anthropology have been discussed below.

Origin of Hereditary variations:

The origin of life occurred three and a half to four billion years ago. The primitive form of life was very simple but slow and gradual process of evolution emergence of more than two million forms of species. Since the species differ in amount and kind of DNA, there must be some ways to change the DNA sequences and new segments being incorporated into genome of organisms. These changes in the hereditary material are known as mutation. The mutation, which do not harm the carriers and modify slightly their ability to survive and reproduce, play important role for evolution. The potential of the mutation process to generate new variation is enormous yet the variation arising in each generation through mutation is small fraction. They can be classified into three categories: Gene/ Point and Chromosomal mutation.

Gene mutation affects only one or a few nucleotides within the gene. It occurs when the DNA sequence of a gene is altered and new nucleotide is passed to the offspring. There are two kinds of gene mutation: base pair substitution and frame shift mutation. Base pair substitution is due to the substitution of one or a few nucleotide pairs for other nucleotides. Such kind of mutations often results in a change in the amino acid sequence of the protein encoded by the gene, but this is not always the case owing to redundancy of the genetic code. Frame shift mutation occurs due to addition or deletion of one or dew nucleotide. It often results in altered sequence of amino acids in the translated protein. The addition or deletion of one or more nucleotide pairs shifts the reading frame of the nucleotide sequence from the point of insertion or deletion the end of the molecule. If one nucleotide pair is inserted at some point and another is deleted, the original reading frames are restored after the mutational change. Gene mutations may occur spontaneously i.e. without intentional causation by humans. Mutations may be induced by UV light, X- rays and other high frequency radiations, as well as by exposing organisms to other chemicals such as mustard gas. These all agents of mutation are known as mutagens. Gene mutations may have effects ranging from negligible to lethal.

Chromosomal   mutation   affects   the   number   or   the   arrangement   of   genes   in   a   chromosome.

Chromosomal mutations can be subdivided into two categories:

1. Changes in location of genes on the chromosome: This is further divided into two groups-Inversion and translocation. Inversion occurs when location of a block of genes is inverted within a chromosome. If the rotated segment includes the centromere, inversion is pericentric; otherwise paracentric. Translocations happen when location of genes is changed in the chromosomes. The most common form of translocation is reciprocal, involving exchange of blocks of genes between non homologous chromosomes. A chromosomal segment may move to a new location without reciprocal exchange. This is known as transposition.
2. Changes in the number of genes in chromosomes

a. Deletion (or deficiency): When a segment of DNA containing one or several genes is lost from a chro: mosome.

b. Duplication: When a segment of DNA containing from one or more genes is present more than once in a set.

3. Changes in number of chromosomes:

There are of four kinds, the first two do not affect the total amount of hereditary material, but the other two do.

a. Fusion: When two non homologous chromosomes fuse into one. This involves loss of one centromere.

b. Fission: When one chromosomes splits into two.

c. Aneuploidy: when one or more chromosomes of a normal set are lacking or in excess. In diploid organisms, terms like Nullisomic, Monosomic, transonic, tetrsomicand so on refer to the occurrence of a given chromosome zero times, once, thrice, four times and so on.

d. Haploidy and polyploidy: When the number of the sets of chromosomes is other than two.

4. Changes in location of genes on the chromosome: This is further divided into two groups-Inversion and translocation. Inversion occurs when location of a block of genes is inverted within a chromosome. If the rotated segment includes the centromere, inversion is peri centric; otherwise Para centric. Translocations happen when location of genes is changed in the chromosomes. The most common form of translocation is reciprocal, involving exchange of blocks of genes between non homologous chromosomes. A chromosomal segment may move to a new location without reciprocal exchange. This is known as transposition.

In addition to mutation, another source of variation is recombination. Recombination is the process through which shuffling of genes between occurs leading to genetic variation. These variations, however, are not transmitted equally from one generation to other. There are processes like gene flow, natural selection and genetic drift which are responsible for transmission of variation to the next generation. However, Hardy- Weinberg law states that no natural selection, no migration(gene flow) and no genetic drift can change the gene frequencies at given locus in a random mating population.

Hardy- Weinberg law: Population genetics has been developed on the basis of this law. G.H. Hardy, a mathematician and Wilhelm Weinberg, a physician, applied rules of Mendel’s to randomly mated population. They expressed their results in the form of Hardy-Weinberg law in 1908. According to this law, gene and genotype frequency in a population does not change from one generation to next, and remains constant. This phenomenon has come to be known as Hardy-Weinberg equilibrium. This principle assumes certain conditions which are:

1.      Mutation must not affect composition of population.

2.      Mating must be random.

3.      Selective forces must not play any role.

4.      The population must be infinitely large.

5.      Population must be in biological isolation.

According to this law, the genotype frequencies are given by the square of the sum of the gene frequencies. If there are two alleles A and a with frequency p and q, the frequencies of the three possible genotype are

frequencies will remain generations after generations- as long as the given conditions are fulfilled. The Hardy-Weinberg law can be extended to multiple alleles.

One of the most important features of Hardy-Weinberg law is that it enables us to express the distribution of genotypes in a population entirely in terms of the gene- frequencies. When a Mendelian population is examined it is almost always found to obey H-W equilibrium. The sample must be very large, or conditions highly unusual, for a deviation from, equilibrium to be detectable. The H-W theorem verifies that in the absence of mutation, selection, or random sampling variations due to finite population size, genetic variation is maintained in a population at its prevailing level and is not eroded. Thus, major processes which lead to change in the gene frequencies down the generations include – Genetic Drift, Gene flow (migration) and Natural selection.

Natural Selection:

Many processes change gene frequency independently of their increasing or decreasing adaptive power. Natural selection is one of the process that act to change the allele frequency of a population. It is the process that promotes adaptation and keeps in check the disorganising effects of other processes. Natural selection is, thus, most critical evolutionary mechanism. Idea of selection as the fundamental process of evolutionary change was independently reached by Charles Darwin and Alfred Wallace. No two individuals are alike. Variations do exist because of mutation or recombination. Some variations are useful in some way so that they increase the likelihood of survival and procreation. Natural selection may be defined as differential reproduction of alternative genetic variants. Natural selection can be of three types- Normalizing, Directional and Diversifying. Normalizing selection occurs when the normal i.e. individual with intermediate phenotypes is favoured and extreme phenotypes are selected against. The phenotypic distribution remains same and that is why it is also called stabilizing selection. In humans, for example, the mortality among newborn infants is highest when they are either very small or very large; infants of moderate size have a better chance of surviving. As a result normalising selection maintains steady genetic constitution. Environment changes over a long period of time. Changes may occur in physical conditions for e.g., climate or biotin conditions..

Environment change promotes genetic changes. The fitness of the variant genotype maybe shifted so that alleles favoured now are different from before; directional selection then comes into operation changing the genetic constitution of the population. Directional selection also operates when organisms colonize a new territory where the conditions are different. Mankind has transformed environment of many organisms. Industrial melanism is one such example. Darkly pigmented moths started to appear in industrial regions where vegetation was blackened by soot.

Natural environment are not homogenous, rather they are mosaics made of more or less similar sub environment. Environment may be heterogeneous with respect to various aspects like climate, food etc. Moreover, heterogeneity may be, temporal or spatial. Temporal environment heterogeneity exists when same organisms experience different environment at different time of their lives. Spatial environment heterogeneity exists when at any time different organisms experience different environment. How is a species to cope with variety of environment it meets both in time and space? One strategy is to have a genotype whose carrier possesses well developed homeostasis thus well adapted in different sub environment. Another strategy is polymorphism – a diversified gene pool with different genotypes I different environment. Natural selection favouring different genotypes in different sub environment is diversifying selection.

The parameter used to measure natural selection is Darwinian fitness or simply fitness. Fitness is a measure of the reproductive efficiency of a genotype relative to the other genotype. It is a measure of how well adapted a particular individual or group is to the requirement imposed by niche. The greater the overall fitness of the individuals, the more their genes tend to be represented in the future generations. This idea is the salient point of evolution of natural selection. The best example of this is sickle – cell disease in regions of the world where malaria is prevalent. The fitness of the sickle cell heterozygotes is higher than either of the homozygotes. The reason being for this is that malarial parasite flourishes less well when cell possess sickle cell haemoglobin. Therefore, heterozygotes A/S are less susceptible to malaria than homozygotes A/A. Though S/S homozygotes are also resistant but they die young. Thus selection is the organizing principle of evolution, producing allele frequency changes that allow population to be better adapted to their environment.

Genetic drift:

Population of organisms consists of limited no. of individuals, though it may be extremely large in some cases. The small size of population causes chance alterations in allele frequencies. This chance changes in allele frequency that results from sampling of gametes from generation to generation in a finite population is known as Genetic drift. This concept of non-directional change in allele frequency is also known as Sewall Wright Effect owing to his contribution to fundamental topics of population genetics. Unlike selection, whether a allele is good or bad, its frequency changes abruptly from one generation to the other. Genetic drift has same expected effect on all loci in the genome. Drift can occur because of chance departures from Mendelian expectation in a few families or because a newly formed isolated group is not representative of the original population. The latter form of drift is known as Founder effect (term coined by Earnest Mayr). Another special case is Bottleneck effect, where a community’s sample of allele frequency is changed due to natural catastrophe, disease or other factors. In a large population on an average, only a small chance change will occur in allele frequency as a result of genetic drift. On the other hand, small population can undergo large fluctuations .Thus genetic drift is dependent on effective size population to pass on the change to net generation.

Wright emphasized that evolution could occur more quickly when a species was broken into small groups. However, a small population with genetic drift will lose the ability to adjust with environment. With regard to human evolution, drift was more important in prehistory when species was broken up into small fragments like hunting camps, tribes and clans.

Gene flow:

Migration is movement of people from one territory to the other. Though immigrants were genetically isolated from the neighbors, some interbreeding took place leading to mixing of genes in subsequent generations. The introduction of new alleles into a population is known as gene flow. Gene flow between populations causes populations to become more similar to each other. Gene flow between populations have led to formation of various groups like American Africans (mixture of Europeans and Africans), Brazilian subgroups which may be the product of the mixture of three groups namely, American Indian, Bantus and Sudanese. Thus, gene flow can be instrumental in elucidating the migrational histories, which took in pre-historic times. Though natural selection is an important mechanism of evolution, but genetic drift and gene flow all these mechanisms do not act in isolation but their interplay influences evolutionary trajectories of populations.

Inbreeding: Exception to Hardy- Weinberg Equilibrium

Population doesn’t mate randomly as assumed. Non random mating, with respect to genotype, occurs in population in which mating individuals are more closely or less closely related than those drawn by chance from the population. The results of these two breeding are called- inbreeding and out breeding. Both the processes don’t cause change in allele frequency but reorganize the alleles into genotypes. In a population that is inbred, frequency of homozygotes is increased and frequency of heterozygotes gets reduced. While in out breeding, the scenario gets reversed. There are certain generalisations regarding inbreeding. First, the genotype changes caused by inbreeding affect all loci in the genome. Genetic drift and gene flow also influence all loci, but selection and mutation influence only single loci. Second, the effect on genotype frequencies may be quite ephemeral if the mating system changes. The high frequency of homozygotes can be eliminated completely in one generation of random mating. Finally, inbreeding and genetic drift appear to have similar overall effects on heterozygosity, but when examining a given locus within a population, the predicted effect is different. Unlike inbreeding, genetic drift may change allele frequency but with no deficiency of heterozygotes within a population. The excess homozygosity comes about because of shared ancestry. Rare recessive genotypes become much more common in inbreeding. This increased proportion of homozygotes influences the fitness of the population due to expression of rare recessive genetic disorders. This decline in fitness due to inbreeding is known as inbreeding depression. The extent of the inbreeding depression varies greatly among different organisms and is influenced by inbreeding and population size.

The usual measure of inbreeding, called the coefficient of inbreeding (f) , was invented by the Sewall Wright. It measures the probability that two homologous alleles in an individual are identical by descent (IBD). Two alleles that have a common history are said to be identical by descent (IBD). The size and sign of the coefficient of inbreeding reflect the deviation from Hardy-Weinberg proportion of the genotypes such that when f is zero, the zygotes are n H-W equilibrium proportions and when f is positive, there is a deficiency of heterozygotes.

Clearly therefore, several forces stated above interact with each other to produce characteristics genetic structure of the populations resulting into genomic and genetic differentials within and between populations. In this context population genetics becomes the key to our understanding of human variation, and by linking medical and evolutionary themes; it enables us to understand the origins and impacts of our genomic differences. Despite current limitations in our knowledge of the locations, sizes and mutational origins of structural variants, the overall growth in this field has brought new insights into recent human adaptation, genome biology and disease association studies. Population genetics provides models for investigating the balance of evolutionary forces acting on genetic diversity. Studies that use these models have found that the evolution of contemporary human genetic diversity has occurred over the past several hundred thousand years or longer. Our species is geographically widespread, but shows low levels of differences among population groups suggesting persistent levels of gene flow as well as dispersal.

Summary

The science of population genetics is an integral component of biological anthropology in understanding human evolution and in pursuing the goal of human origins vis-à-vis the divergence of human groups, Population genetics is the key to our understanding of human variation, and by linking medical and evolutionary themes; it enables us to understand the origins and impacts of our genomic differences. Despite current limitations in our knowledge of the locations, sizes and mutational origins of structural variants, the overall growth in this field has brought new insights into recent human adaptation, genome biology and disease association studies. Population genetics provides models for investigating the balance of evolutionary forces acting on genetic diversity. Studies that use these models have found that the evolution of contemporary human genetic diversity has occurred over the past several hundred thousand years or longer. Our species is geographically widespread, but shows low levels of differences among population groups suggesting persistent levels of gene flow as well as dispersal.

References:

• Mange, a.p. And e.j. Mange. 1998. Basic human genetics, second edition. Sinauer publishing, Sunderland, ma.
• Hedrick, p. 2004. Genetics of population. Third edition. Ones & Bartlett learning publishing. Cavalli-sforza, l., 1999. The genetics of human populations, Dover publications, New York. Weblinks:
• Boundless. “Stabilizing, directional, and diversifying selection.” Boundless biology. Boundless, 14 Nov. 2014. Retrieved 10 may. 2015 from https://www.boundless.com/biology/textbooks/boundless-biology-textbook/the-evolution-of-populations-19/adaptive-evolution-132/stabilizing-directional-and-diversifying-selection-535-11742/