Evolutionary Forces: Mutation, Selection, Genetic Drift, Gene Flow and Isolation

Evolution is change in the genetic composition of populations over generations. Six forces shape human genetic variation. Mutation creates new variants and recombination reshuffles them. Natural selection changes their frequencies according to fitness, and genetic drift changes them by chance, most strongly in small populations. Gene flow spreads variants between populations and makes them alike. Non-random mating, including inbreeding, rearranges variants into genotypes. Isolation, by limiting gene flow, lets drift and selection make populations differ.

This is a complete study note on the evolutionary forces for the UPSC Anthropology Optional, covering mutation, recombination, natural selection, genetic drift with founder effect and bottleneck, isolation and genetic isolates, gene flow and admixture, and non-random mating, with human case studies. It falls under Paper I, topic 9.3 (causes and changes which bring down frequency: mutation, isolation, migration, selection, inbreeding and genetic drift) of the Anthropology Optional syllabus, and it supports topic 9.4 on chromosomal aberrations and inborn errors.

Key points at a glance

• Raw material: genetic variation is the substrate of evolution. Without it no force can act.
• Mutation: the ultimate source of all new variation; rare, random and recurrent.
• Recombination: creates new combinations of existing alleles at meiosis.
• Natural selection: differential survival and reproduction; the only force that produces adaptation.
• Genetic drift: random change in allele frequencies; strongest in small populations. Founder effect and bottleneck are its special cases.
• Isolation: not a force in itself, but the condition under which drift, selection and inbreeding make a population diverge.
• Gene flow: movement of alleles between populations; reduces differences between them and adds variation within them.
• Non-random mating: inbreeding and assortative mating change genotype frequencies, not allele frequencies.
• Balance: real populations reflect the combined action of all the forces, such as mutation against selection, and drift against gene flow.

Variation, equilibrium and the forces of change

In the context of evolution, the existence of genetic variation is all-important, because it is what evolution works on. The Hardy-Weinberg law describes a population in which nothing is happening: it is large, mates at random, and experiences no mutation, selection or migration, so its allele and genotype frequencies stay the same. Each evolutionary force is a departure from one of those conditions.

The table is worth memorising. Most questions on this topic can be answered from it.

1. Mutation

A mutation is a sudden, heritable change in the genetic material that is not the result of recombination. The process of producing it is mutagenesis, an agent that causes it is a mutagen, and an organism showing its effect is a mutant. Hugo de Vries introduced the term at the start of the 20th century. The human genome is not static: without heritable change, life could not have evolved and diversified. Mutation is the ultimate source of all genetic variation and supplies the raw material of evolution.

General characteristics of mutation

• Random. Mutations occur without regard to whether they would be useful. They may arise at any time and in any cell.
• Rare. The rate at any one gene is very low in each generation.
• Recurrent. The same mutation can arise again and again.
• Mostly recessive, though dominant mutations also occur.
• Mostly neutral or harmful. A random change to a working system is more likely to damage it than to improve it. A small minority are beneficial, and these are what selection builds on.
• Reversible. A mutant allele can mutate back (reverse mutation), though usually at a lower rate.

Stage at which a mutation occurs

Only germ-line mutations matter for evolution, because only they are inherited.

Classification of mutations

Types by the method of detection

• Morphological mutation: alters outward appearance, such as colour, shape or size.
• Lethal mutation: causes the death of the individual; useful for measuring mutation frequency.
• Biochemical mutation: causes a deficiency in a metabolic step, which can often be made good by supplying the missing substance.
• Resistant mutation: enables growth in the presence of a pathogen or an antibiotic.
• Conditional mutation: shows its effect only under certain conditions, such as high temperature.

Mutation at the molecular level

At the level of DNA, a mutation is a permanent change in the sequence of nucleotides. The possible changes are deletion of bases, insertion of bases, inversion of a sequence, and replacement of one base pair by another.

Base substitution (point mutation)

A point mutation in a coding region can have three kinds of effect on the protein.

Frameshift mutation

The genetic code is read in triplets. The insertion or deletion of bases, unless in multiples of three, shifts the reading frame of every codon that follows. In most cases no functional protein is made.

Tautomeric shifts

Watson and Crick pointed out that the bases of DNA are not chemically fixed. A hydrogen atom can move from one position to another within a base. In its rare form a base pairs with the wrong partner at replication, and a transition results. This is one source of spontaneous mutation.

Spontaneous and induced mutation

• Spontaneous mutations arise without exposure to any known external agent. Their sources are errors in DNA replication, spontaneous chemical damage to bases, and the movement of transposable elements. They are the ultimate source of natural variation in populations.
• Induced mutations are caused by an external mutagen that alters the DNA.

Mutation at the biochemical level

Genes control traits by controlling the synthesis of proteins. Archibald Garrod, studying alkaptonuria, introduced the idea of "inborn errors of metabolism" in the first decade of the 20th century. G. W. Beadle and E. L. Tatum, working with the mould Neurospora in 1941, showed that each step of a metabolic pathway is controlled by an enzyme, and each enzyme by a gene. This is the one gene, one enzyme hypothesis.

Inborn errors of metabolism are single-gene disorders, usually autosomal recessive or X-linked recessive, in which a missing or defective enzyme blocks a metabolic pathway.

All three lie on the pathway that begins with phenylalanine, which is why they are usually taught together.

Chromosomal mutations

Some mutations affect whole chromosomes or large parts of them.

Such conditions greatly reduce reproductive fitness, so they are not passed on in the ordinary way. Their frequency at birth therefore reflects the rate at which they arise anew.

Kinds of DNA variation used in anthropology

Molecular anthropology compares DNA sequences to work out how closely populations, and species, are related, and to trace migration and settlement. The variants differ in the number of bases affected and in how they arise.

Polymorphism. A locus is called polymorphic when its commonest allele has a frequency of 99 per cent or less, that is, when at least one other allele reaches 1 per cent (Masatoshi Nei). Rarer variants are simply called rare variants.

Mutation as an evolutionary force

• It is indispensable. Every allele that any other force acts on began as a mutation.
• It is weak. Because rates are so low, mutation alone changes allele frequencies very slowly. A new mutation is a single copy in the whole population; whether it spreads depends on drift and selection.
• It is a clock. Neutral mutations accumulate at a roughly steady rate, which lets anthropologists estimate when two populations or species diverged.

Mutation rate and how it is estimated

The mutation rate is the frequency with which a new mutation arises at a locus in each generation. For a single human gene it is very low, in the order of one in a hundred thousand to one in a million gametes; for a single base it is far lower still. Because the genome is so large, every person nevertheless carries some tens of new mutations not present in either parent.

The rate rises with the father's age, because the cells that produce sperm go on dividing throughout life. Haldane was the first to notice that mutation is more frequent in the male line.

Deleterious mutation and the balance with selection

Many genetic diseases, dominant and recessive, are known, and all are individually rare. They persist because new copies arise by mutation as fast as selection removes the old.

A dominant condition: achondroplasia

• Achondroplasia, a form of short-limbed dwarfism, occurs at a low frequency in nearly all human populations, in the order of one birth in tens of thousands.
• The gene is dominant, so every person who carries it is affected. Affected individuals are heterozygotes.
• Selection acts against it mainly through reduced reproduction: affected persons have, on average, fewer children. It does not act chiefly through early death.
• Most affected children are born to two unaffected parents. These cases are new mutations.
• Because a dominant mutation shows itself at once, the mutation rate can be estimated directly by counting such births.

The frequency of the condition stays low and steady because mutation supplies new copies in each generation and selection removes them at the same rate. This is mutation-selection balance.

Recessive conditions

A harmful recessive allele is exposed to selection only in homozygotes. If its frequency q is 0.01, the proportion of affected homozygotes is q², or 1 in 10,000, while nearly 2 per cent of the population are unaffected carriers. Selection therefore removes recessive alleles very slowly, and they can reach higher frequencies than dominant ones before a balance is struck. This is also why inbreeding, which increases homozygosity, raises the incidence of recessive disorders.

2. Recombination

Genetic recombination is the exchange of segments between homologous chromosomes during meiosis, by crossing over. Together with the independent assortment of chromosomes, it ensures that each gamete carries a new combination of the alleles the parent received.

• What it does. It creates no new alleles, but it produces new combinations of existing ones, and so increases the variety of genotypes on which selection can act.
• Linkage. Alleles at loci that lie close together on a chromosome are rarely separated and tend to be inherited as a block, called a haplotype. The non-random association of alleles at different loci is linkage disequilibrium.
• Hitchhiking. Because of linkage, a force acting on one locus affects its neighbours. When selection raises the frequency of a favourable allele, neutral alleles linked to it rise with it.
• Selective sweep. As the favoured allele reaches fixation, variation in the surrounding region is wiped out. A stretch of unusually low diversity is therefore a sign of recent selection.
• Hotspots. Recombination is not spread evenly along chromosomes. It is concentrated in short regions called recombination hotspots.

Use in anthropology. Linkage disequilibrium decays with each generation of recombination, so its extent tells how long ago a population was founded or mixed. Mitochondrial DNA and most of the Y chromosome do not recombine at all. They pass intact down the female and the male line, which is why they are used to trace maternal and paternal ancestry.

3. Natural selection

Natural selection is Charles Darwin's contribution to evolutionary theory. It is the differential survival and reproduction of individuals with different genotypes. It occurs when genotypes differ in fitness, the probability of surviving and reproducing, so that allele frequencies change over time. Selection acts directly on phenotypes, and through them on the genes that underlie them. It is the only force that makes populations better suited to their environment.

Fitness and the selection coefficient

• Fitness has several components: viability (survival to reproductive age), success in finding a mate, fertility and fecundity.
• Relative fitness (w) compares a genotype with the fittest genotype, which is given the value 1.
• Selection coefficient (s) measures the disadvantage of a genotype: s = 1 − w. A lethal genotype has s = 1.
• Fisher's theorem. R. A. Fisher (1930) showed that the rate of evolution by natural selection is proportional to the genetic variation in fitness. No variation, no selection.

The classic field example is the peppered moth in England. As soot darkened tree trunks during industrialisation, the dark form, better hidden from birds, replaced the pale form; with cleaner air the pale form has returned.

Types of natural selection

Balanced polymorphism: sickle cell and malaria

The best-studied case of selection in humans is haemoglobin S.

A. C. Allison showed in 1954 that carriers of the trait are protected against malaria. Because the heterozygote has the advantage, selection keeps both alleles in the population, a balanced polymorphism. Frank Livingstone later linked the spread of the allele in West Africa to the clearing of forest for agriculture, which created breeding places for the mosquito: a case of culture changing the direction of selection. In India the allele is frequent among several tribal populations of the central, western and southern belts. Where malaria is controlled, the advantage disappears and the allele slowly declines.

Other examples of selection in humans

Detecting selection in the genome

• Two approaches. Researchers examine candidate genes of known function, or scan the whole genome for unusual patterns.
• The signatures. Reduced diversity around a gene (a selective sweep), long unbroken haplotypes, and unusually large frequency differences between populations.
• Telling selection from history. Demographic events such as bottlenecks and expansions affect the whole genome alike. Selection affects only the region around the selected gene. A pattern confined to one region therefore points to selection.

Selection in modern populations

Medicine, sanitation and food security have relaxed selection against many conditions. Selection has not stopped: differences in fertility and in survival from infectious and chronic disease continue to exist. Culture has become the main means of human adaptation, and it changes the selective pressures that genes face.

4. Genetic drift

Genetic drift is random change in allele frequencies from one generation to the next. It is a stochastic process: each generation is formed from a sample of the gametes of the one before, and a sample never reproduces the original proportions exactly. The idea was developed largely by Sewall Wright from the 1930s, and drift is sometimes called the Sewall Wright effect. Motoo Kimura extended the mathematics from the 1950s.

Drift is evolution without adaptation. One allele rises and another falls, not because either is better, but by chance. It is like reaching into a bag of mixed sweets and happening to draw mostly one colour.

The model

Wright (1931) described drift using an idealised population: finite, constant in size, with generations that do not overlap, and with all individuals equally fit. Real populations are compared with this ideal through the effective population size (N_e), the size of an ideal population that would show the same amount of drift. N_e allows drift to be compared between populations. It also differs between parts of the genome: it is smaller for mitochondrial DNA and the Y chromosome, which are passed on by one sex only, so these drift faster.

Properties of genetic drift

• It is random in direction. Which allele will increase cannot be predicted.
• Its strength depends on population size. The smaller the population, the larger the chance fluctuations.
• It ends in fixation or loss. Given time, one allele is fixed and the others are lost. The chance that a neutral allele is eventually fixed equals its present frequency.
• It reduces variation within a population. Heterozygosity falls each generation, faster in small populations.
• It increases differences between populations. Separate populations drift in different directions, so the proportion of alleles they share falls.
• It can override weak selection. In a small population a mildly harmful allele may be fixed, or a mildly useful one lost, by chance.

Conditions under which drift operates

1. The alleles concerned have little or no selective difference.
2. The population is small and reproduces sexually.
3. There is little immigration or emigration.

Drift occurs when numbers fall sharply, through migration of a small group, a natural disaster, or isolation by a geographical or social barrier. It is not confined to remote places. Within large cities, communities that marry among themselves keep their own genetic variants.

Founder effect

The founder effect, a term due to Ernst Mayr, is the form of drift that occurs when a small group leaves a larger population and founds a new one. The founders carry only a sample of the original gene pool, and their descendants inherit that sample, whatever it happens to contain. Differences between the new population and the old may therefore owe nothing to adaptation. The founder effect shows how much history, as well as environment, shapes evolution.

How founder effects are recognised:

• Phenotypically. A community known from history to descend from a few founders has conditions that are rare elsewhere.
• From allele frequencies. Its frequencies differ sharply from those of the parent population.
• From a single mutation. All affected persons carry the identical mutation. A population with several different mutations causing the same disorder has more probably received them from several sources.
• From shared haplotypes. The DNA surrounding the gene is also identical, showing that a whole chromosome segment has come down from a common ancestor.

Examples are given in the section on isolates below.

Population bottleneck

A bottleneck occurs when a population is sharply reduced, by catastrophe, disease or famine, and later recovers from the few survivors. The recovered population carries only the alleles the survivors happened to have. Some variants are amplified and others lost, and the gene pool is narrower than before.

• Pingelap. On this Micronesian atoll a typhoon in the late 18th century, and the famine that followed, left about twenty survivors. One of them carried a recessive allele for complete colour blindness (achromatopsia). Today several per cent of the islanders are affected and a large proportion are carriers, against a world frequency of about one in tens of thousands.
• The human species. As modern humans spread out of Africa, each new region was settled by a small group drawn from the one before. Genetic diversity therefore declines with distance from Africa, and African populations remain the most diverse. This pattern is called a serial founder effect.
• Cheetahs. Living cheetahs are so alike genetically that unrelated animals accept skin grafts from one another, a result attributed to severe bottlenecks in their past.

Consequences of genetic drift

• Loss of genetic variation, which may reduce a population's capacity to respond to new selective pressures. This matters especially for small and endangered populations.
• Loss of heterozygosity and a rise in homozygosity. Long chromosome regions that are identical on both copies, called runs of homozygosity, mark populations that have passed through small numbers.
• Raised frequency of particular recessive disorders.
• Increased variance among populations.
• A possible contribution to the formation of new species, when a small isolated population diverges.

A note on terms. In medical genetics, "loss of heterozygosity" also names an event in body cells, in which a cell that had one working and one faulty copy of a gene loses the working copy. It is studied in cancer. That is a somatic change within one person and is distinct from the loss of heterozygosity in populations discussed here.

Drift, selection and the neutral theory

Drift and selection are the two main causes of the replacement of one allele by another. Selection produces adaptation; drift does not. Drift cannot explain the anatomical, physiological and behavioural features that fit organisms to their way of life.

At the molecular level its role is large. Motoo Kimura's neutral theory of molecular evolution (1968) holds that most differences in DNA and protein sequence, within and between species, are selectively neutral and have spread by drift. Because every population is finite, all loci are subject to drift, while only some are subject to selection. Many geneticists therefore treat drift as the null hypothesis: a difference between populations should not be called adaptive unless there is positive evidence that selection produced it.

5. Isolation and genetic isolates

Isolation is the restriction of gene flow between populations. It is not a force that changes allele frequencies by itself. It is the condition that allows drift, selection and inbreeding to make a population different from its neighbours, and if it lasts long enough it is the first step towards the formation of a new species.

Kinds of isolation

In our species cultural barriers are now more important than geographical ones. Religious practice in particular can produce genetic isolation without any geographical separation.

What a genetic isolate is

A genetic isolate is a sub-population that arose from a small number of founders, usually after some bottleneck, and has since lived in geographical or cultural isolation for many generations with little genetic exchange. Two processes recur in such a population: inbreeding, and the sampling of gametes in each generation, that is, drift. Together they produce micro-differentiation, a population that stands apart genetically from those around it.

Why no real population is in perfect equilibrium

1. No population is infinitely large, and mating is never fully random. People marry those who live near them and those of similar social and economic position. Even in a cosmopolitan city, marriage is patterned by distance and by community.
2. Mutation and selection operate. Across many loci, mutation generates diversity quickly, and selection has demonstrably acted at loci such as those for thalassaemia and the Duffy blood group in malarial regions.
3. Migration is patterned. Movement over short distances is easier than over long ones, so neighbouring populations resemble each other. New settlements are typically founded by a few people, grow rapidly, and become cut off by mountains, sea or desert, or by language and religion.

Why isolates matter for genetic research

• Most arise from a founder effect, so affected persons usually share one mutation.
• Inbreeding raises the incidence of recessive disorders, making cases easier to find.
• Large, well-documented pedigrees extend over many generations.
• Members share a similar environment and way of life, which reduces non-genetic variation.
• Linkage disequilibrium extends over longer stretches of the chromosome, which helps to locate disease genes.

The first successes came with rare Mendelian recessive disorders, notably among the Finns and the Amish. Isolates have since been used to search for genes that contribute to common complex conditions such as asthma, high blood pressure and psychiatric disorders, though with less success than for single-gene disorders.

Selected isolates

The Finns

• Origins. Two models have been proposed. The first assumes a single settlement about 2,000 years ago by a small number of people from south of the Gulf of Finland. The second, the dual-origin model, assumes an earlier movement of eastern Uralic speakers some 4,000 years ago, followed by a later one from the south. Y-chromosome haplotypes and archaeological differences between eastern and western Finland support the second.
• Language. Finnish belongs to the Uralic family and is not Indo-European, a sign of long separation from most of Europe.
• Demography. Internal migration was slight until the 17th century. Growth was interrupted by war, famine and disease. In the last 300 years the population has grown from about a quarter of a million to more than five million.
• Result. Recessive disorders are unevenly distributed across the country, consistent with internal isolates. The study of the Finns is the most successful example of mapping disease genes in a population isolate.

The Old Order Amish

• A religious isolate descended from a limited number of founders who came to North America from the Rhineland, having earlier left Switzerland.
• In Lancaster County, Pennsylvania, Victor McKusick documented a high incidence of Ellis-van Creveld syndrome, a recessive form of dwarfism with extra fingers. In a population of about 13,000 he recorded 82 affected persons in 40 sibships.
• All 80 parents in those families traced their descent to one early couple, Samuel King and his wife. One of the two must have carried the allele.
• McKusick also recognised a new syndrome, cartilage-hair hypoplasia, in this community. Other rare metabolic disorders are far more frequent among the Amish and Mennonites of the county than in the general population.
• Because the causes are known, treatment, from special diets to newer therapies, has followed.

The Hutterites

• An Anabaptist group that originated in the Tyrol in the 16th century and moved eastward under religious persecution, reaching Ukraine.
• They migrated to North America between 1874 and 1877. A few hundred who chose to live communally, with a handful of later joiners, are the ancestors of the present population, which now exceeds 40,000.
• They are endogamous and divided into three kinship groups: the Schmiedeleut, the Dariusleut and the Lehrerleut. They live in communal farming colonies in Canada and the United States.
• Their uniform diet and way of life make them valuable for studying complex disorders. Carole Ober and colleagues have studied asthma, fertility and many quantitative traits. An excess of heterozygotes at HLA loci has been interpreted as the result of mating between people with different HLA types.

Tristan da Cunha

• A small volcanic island in the South Atlantic, among the most remote inhabited places on earth. Its population of about 300 descends from a handful of settlers who arrived in the 19th and early 20th centuries.
• Genealogies show that only seven women left descendants. Because mitochondrial DNA passes through the mother without recombination, living islanders' mitochondrial types can be matched to the founding women. Himla Soodyall and colleagues found five types where the records predicted four, showing that two women recorded as sisters were not maternal sisters.
• The island has seven surnames, one for each founding father. Y-chromosome haplotypes matched the surnames in most cases; the exceptions revealed a later male migrant and a few cases in which the recorded father was not the biological father.

The island shows, on a very small scale, how genealogical records and DNA can check each other.

The Paisa community of Colombia

• A community of the Andean region of Antioquia, sharing cultural and demographic features, that remained relatively isolated from the rest of Colombia.
• It descends from multiple founder families of about twenty generations ago. Its historical origins are mainly Spanish, including Basques and converted Sephardic Jews, with Amerindian ancestry entering mostly through the maternal line.
• Very large families and deep genealogies make it one of the important populations for gene mapping.
• It illustrates a point of theory: admixture and isolation both create linkage disequilibrium. A population founded by a mixture and then isolated keeps long-range associations between loci, which can be used to map genes by admixture.

French Canadians

• The French founded Quebec City in 1608. The population grew by immigration from France until about 1660 and thereafter mainly by births, from a few thousand founders to about six million.
• Religion and language kept the French and English gene pools apart.
• Of the many mutations known worldwide in the breast-cancer gene BRCA1, only a handful account for most cases among French Canadians.
• In the 19th century some families moved to newly opened land north of Quebec City. Their descendants form an even more uniform sub-population: a founder effect within a founder effect.

Afrikaners and other founder populations

• Afrikaners. The Afrikaner population descends from a small group of Dutch, French and German settlers with very large families. Porphyria variegata, a dominant condition, affects many thousands, all traced to one couple who married at the Cape in 1688. Its frequency is far higher than in the Netherlands.
• Ashkenazi Jews. Almost all cases of BRCA1 breast cancer in this population are due to one of a small number of founder mutations.
• West African ancestry. A particular BRCA1 mutation is shared by families in West Africa, the Bahamas and the south-eastern United States. It was carried across the Atlantic by people taken in the slave trade, and persists in their descendants and in those of relatives who remained in Africa.

6. Gene flow (migration)

Gene flow is the transfer of alleles from one population to another. Migration is the movement of people; it becomes gene flow only when the migrants have children in the new place. Gene flow can be seen as the glue that holds the populations of a species together. Its reduction or removal is necessary for speciation to begin.

Effects of gene flow

• It introduces new alleles. Mutation is the ultimate source of new alleles, but gene flow spreads a new mutant from the population where it arose to others, where drift and selection act on it afresh.
• It reduces differences between populations. This is its main effect. John Relethford's analogy is two cans of paint, one red and one white. Exchange a cup between them and mix; the red becomes slightly paler and the white slightly pink. Repeat often enough and both cans are the same shade. Alleles do not blend as paint does, but the frequencies converge in the same way.
• It increases variation within the receiving population.
• It opposes drift. Even a little gene flow prevents small populations from diverging by chance.
• It may oppose local adaptation, by bringing in alleles that are not suited to local conditions.
• It prevents speciation, by keeping populations genetically connected.

Models of gene flow

Human reality. Human settlement is uneven and falls between the discrete groups of the stepping-stone model and the continuity of isolation by distance. Migration includes long-distance moves as well as local choice of spouses. It responds to "push" and "pull" factors, is rarely equal in both directions, and is often biased by age and sex. Because detailed records of migration and of marital distance exist for humans, these models can be tested directly.

Admixture

Admixture occurs when individuals from two or more populations that were previously separate begin to interbreed. Many human populations were formed in this way through the major migrations of history.

• Character of an admixed population. Its allele frequencies generally lie between those of the parental populations.
• Admixture proportion. The share of the gene pool derived from each parental population. It is also called the accumulated admixture level.
• Admixture rate. The proportion entering per generation. If the time since mixing began is known, the accumulated proportion can be converted into a rate.
• Individuals differ. A population average does not describe each member. Every person has his or her own ancestry.

Estimates are best made from alleles that differ greatly in frequency between the parental populations. Bernstein's classical formula gives the proportion from one parent as the difference between the admixed and one parental frequency, divided by the difference between the two parental frequencies.

Case studies of gene flow and admixture

The peopling of the Americas

• The question. When Europeans reached the Americas at the end of the 15th century, the origin of the peoples they met was unknown, and fanciful suggestions were made. Some early writers correctly pointed to north-eastern Asia, since the two continents nearly meet at the Bering Strait.
• The route. During glacial periods the sea level fell and exposed land joining Siberia and Alaska (Beringia). The long-favoured view was that hunters crossed this land bridge and moved south through an ice-free corridor about 12,000 to 13,000 years ago.
• Revision. Sites now dated to 15,000 years ago or earlier show that people were present before that corridor opened. Many archaeologists therefore favour an earlier movement along the Pacific coast, possibly using boats.
• The genetic evidence. Whatever the timing and route, a north-east Asian origin is not in doubt. On classical blood-group and protein markers, and on DNA, Native American populations are genetically closest to the populations of East Asia and of the north-eastern Arctic, and more distant from those of Europe, Africa and Australia.

The origin of the Irish Travellers

• The Irish Travellers are a traditionally itinerant community forming well under one per cent of the population of Ireland.
• Two hypotheses. One held that they descend from Irish people displaced from the land who became a separate social group. The other held that they are related to the Roma.
• The test. Michael Crawford and George Gmelch (1974) computed genetic distances from red-cell markers. The Travellers were closest to other Irish populations and distinct from Roma groups. Later analyses agreed.
• The lesson. A similar way of life does not indicate common ancestry. Culture and genes vary independently.
• Drift. The community's small size and uneven family sizes give it a low effective population size. A mutation causing galactosaemia is about ten times more frequent among Travellers than among other Irish people. It arose in Ireland and was raised in frequency by founder effect and continued drift.

Admixture in African Americans

• History. From the early 17th century to the early 19th, very large numbers of Africans were enslaved and transported to North America. Gene flow from people of European descent took place during slavery and afterwards.
• Estimates. Esteban Parra and colleagues (1998) used markers that differ strongly in frequency between Europeans and West Africans. In ten African American populations the accumulated European ancestry ranged from about 12 per cent in Charleston, South Carolina, to about 23 per cent in New Orleans. There is no single figure; each community has its own history.
• Sex bias. European ancestry was much higher in Y-chromosome markers, which trace the male line, than in mitochondrial DNA, which traces the female line. The gene flow was therefore mainly from men of European descent to women of African descent, which reflects the coercive conditions of slavery.
• Individual variation. In one South Carolina city the population average was about 18 per cent, but most individuals had less than 10 per cent and a few had more than half. Among the more isolated Gullah of the coast, European ancestry was lower still.

A population estimate is a statistical average of many individual histories. It does not describe any one person.

7. Non-random mating

The Hardy-Weinberg law assumes random mating. People do not choose partners at random. Non-random mating does not by itself change allele frequencies. It changes the way alleles are combined into genotypes, and so changes the proportion of homozygotes and heterozygotes on which selection then acts.

Assortative mating

Assortative mating occurs when partners resemble each other, or differ from each other, more than would be expected by chance.

Sewall Wright (1921) showed that positive assortative mating increases the genetic contribution to the variance of polygenic traits.

Inbreeding

Inbreeding is mating between relatives, that is, between individuals who share one or more recent common ancestors.

• Inbreeding coefficient (F). Wright defined F as the probability that the two alleles a person carries at a locus are identical by descent, that is, copies of the same allele in a common ancestor.
• Effect on genotypes. Heterozygosity falls from 2pq to 2pq(1 − F), and both kinds of homozygote increase. Allele frequencies stay the same.
• Effect on health. Recessive disorders become more frequent, and average fitness may fall. This is inbreeding depression.

Assortative mating and inbreeding compared

The two overlap, since relatives tend to resemble one another, but they are not the same thing.

Inbreeding in human populations

• By preference. Cross-cousin and uncle-niece marriage in South India, and parallel-cousin marriage in parts of West Asia, raise the average inbreeding coefficient.
• By necessity. In a small isolate everyone is related, so spouses are relatives even where close-kin marriage is avoided.
• Reduced by rule. Clan and gotra exogamy and the wide prohibited degrees of North India lower inbreeding.

Here the rules of marriage studied by social anthropology have direct genetic consequences.

How the forces act together

No force acts alone. The genetic structure of a real population is the outcome of several forces in balance.

Wright's shifting balance

Sewall Wright combined the forces in one theory. A species divided into many small, partly isolated populations evolves most effectively. Drift lets some populations arrive at new and favourable combinations of genes; selection then raises those combinations within them; and migration carries the gain to other populations. Human populations through most of prehistory, small bands linked by occasional intermarriage, fit this picture.

The measure of differentiation

Wright's fixation index, F_ST, measures how much of the total genetic variation lies between populations. It rises with drift and isolation and falls with gene flow. Among human populations it is low: most variation is found within any one population, and only a small part distinguishes populations from one another, as Richard Lewontin showed in 1972. This reflects our recent common origin and continued gene flow. See our note on the human fossil record for the evolutionary background.

Microevolution and macroevolution

• Microevolution is change in allele frequencies within a species, the subject of this note.
• Macroevolution is the origin of new species and higher groups. In the modern synthesis it results from the same forces acting over long periods, with isolation leading to reproductive separation.

From isolation to new species

When gene flow between two populations stops for long enough, mutation, drift and selection carry them in different directions until their members can no longer interbreed. At that point they are separate species. Ernst Mayr made this the centre of his account of speciation.

Living humans form a single species. No human population has been isolated for long enough, or completely enough, to approach this point, and gene flow has always reconnected the populations that distance or culture kept apart. The evidence that modern humans interbred with Neanderthals shows that even those populations had not become fully separate.

Why the forces matter: applications

• Reconstructing history. The pattern of mutations in mitochondrial DNA and the Y chromosome, and the decay of linkage disequilibrium, are used to date migrations, admixture events and the founding of populations.
• Understanding human variation. Differences between populations in blood groups, pigmentation or disease are explained by named forces, not by fixed racial types.
• Public health. Knowing that a founder mutation is common in a community allows targeted screening of newborns and carriers, as for sickle-cell disease and thalassaemia in India.
• Genetic counselling. The inbreeding coefficient gives the added risk to the children of related parents.
• Gene mapping. Isolates and admixed populations are used to locate the genes behind inherited disorders.
• Forensic science. Identification by DNA depends on knowing how frequent each variant is in the relevant population.
• Conservation. Small, isolated populations of endangered species lose variation by drift and suffer from inbreeding, which guides how they are managed.

The evolutionary forces in Indian populations

• Founder effect and drift. India's thousands of endogamous castes and tribes have each passed through their own history of small numbers. Genome studies have found strong founder effects in many of them, and recessive disorders that are particular to single communities.
• Small tribal isolates. The peoples of the Andaman Islands and the Toda of the Nilgiris have very small breeding populations in which drift is powerful.
• Selection. The sickle-cell allele reaches high frequency among tribal populations of central, western and southern India, in regions with a long history of malaria. Beta-thalassaemia and G6PD deficiency show similar regional and community patterns.
• Gene flow and admixture. Most Indian populations derive from the mixing of a small number of ancestral groups, followed by a long period of endogamy. A clear recent case is the Siddi of western and southern India, who have substantial African ancestry together with South Asian ancestry.
• Inbreeding. Consanguineous marriage is common in the southern states and among some communities elsewhere, and rare in much of the north, a contrast that follows the kinship zones described by Irawati Karve.
• Isolation by culture. Caste and tribe endogamy have acted as barriers as effective as any mountain range, and have preserved differences between groups living side by side.

For present-day issues among tribal communities, including health programmes for sickle-cell disease, see tribal India today.

Worked illustrations

Drift in a small and a large population

Suppose an allele has a frequency of 0.5. In a breeding population of ten people there are only twenty copies of the gene, and the next generation is a sample of twenty. By chance alone it may contain eight or thirteen copies of the allele instead of ten, moving the frequency to 0.4 or 0.65 in a single generation. In a breeding population of ten thousand, the same chance variation moves the frequency by a fraction of one per cent. Repeated over generations, the small population soon loses one allele altogether, while the large one hardly changes.

Gene flow in the island model

Suppose an allele has a frequency of 0.2 on an island and 0.8 on the mainland, and that in each generation one-tenth of the island's parents are migrants from the mainland. The island's new frequency is nine-tenths of 0.2 plus one-tenth of 0.8, which is 0.26. In the following generation it is 0.314, and it continues to climb, by smaller steps each time, towards 0.8. The difference between island and mainland shrinks by one-tenth in every generation.

Inbreeding and a recessive disorder

If a recessive allele has a frequency of 0.01, one child in 10,000 of unrelated parents is affected. For the children of first cousins, where F is 1/16, the expected proportion is about seven in 10,000. The allele is no more common than before; inbreeding has only brought two copies together more often.

The forces in human evolution

Drift, selection and gene flow compared

Glossary

Key thinkers at a glance

Using this topic in a UPSC answer

• Start from equilibrium. State the Hardy-Weinberg conditions, then present each force as the breach of one condition.
• Use the summary table. For each force give its effect within populations, its effect between populations, and whether it is adaptive.
• One human example each: achondroplasia for mutation; sickle cell for selection; Pingelap or the Amish for drift; African American admixture or the peopling of the Americas for gene flow; cousin marriage for inbreeding.
• Distinguish the pairs: founder effect and bottleneck; assortative mating and inbreeding; migration and gene flow; admixture proportion and admixture rate.
• Show interaction. Mention mutation-selection balance and the opposition of drift and gene flow.
• Add India. Endogamy as cultural isolation; sickle cell among tribes; consanguinity in the south.
• Draw simply. A wide bottle narrowing to a neck for the bottleneck; two circles with arrows for gene flow.

For presentation, see our guide to anthropology answer writing with diagrams, thinkers and case studies.

Common mistakes to avoid

• Saying that mutations occur because they are needed. Mutation is random with respect to need; selection is what sorts the useful from the harmful.
• Treating drift as a weak form of selection. Drift is chance and has nothing to do with fitness.
• Equating migration with gene flow. Migrants who leave no children contribute no genes.
• Claiming that inbreeding changes allele frequencies. It changes genotype frequencies only; selection acting on the exposed homozygotes is what then changes allele frequencies.
• Calling isolation a force. It is a condition that lets the forces act differently in separated populations.
• Confusing founder effect with bottleneck. One involves a move to a new place, the other a collapse in the same place.
• Describing selection as acting on genes directly. It acts on phenotypes, and through them on genotypes.
• Applying a population average to an individual. An admixture proportion or a disease frequency describes the group, not any one member.
• Writing that evolution has a goal. The forces have no foresight; adaptation is the outcome of selection acting on variation that happened to be available.

Practice questions

1. Discuss the factors that bring about changes in gene frequencies in human populations.
2. What is genetic drift? Explain founder effect and bottleneck with human examples.
3. Mutation is the ultimate source of variation but a weak force of evolution. Comment.
4. Explain balanced polymorphism with reference to the sickle-cell trait.
5. Distinguish between gene flow and genetic drift in their effects on genetic variation.
6. What are genetic isolates? Discuss their importance in human genetic research.
7. Describe the models of gene flow and their relevance to human populations.
8. How does inbreeding differ from assortative mating? Discuss the genetic consequences of consanguineous marriage.
9. Write short notes on: (a) mutation-selection balance, (b) the neutral theory, (c) admixture.

Frequently asked questions

What are the evolutionary forces?

The evolutionary forces are the processes that change the genetic make-up of populations: mutation, recombination, natural selection, genetic drift, gene flow and non-random mating. Isolation is the condition that allows them to make populations diverge.

Which evolutionary force creates new alleles?

Only mutation creates new alleles. Recombination creates new combinations of existing alleles, and gene flow brings into a population alleles that arose elsewhere.

What is genetic drift?

Genetic drift is random change in allele frequencies from one generation to the next, caused by chance in the sampling of gametes. It is strongest in small populations and does not produce adaptation.

What is the difference between founder effect and bottleneck?

In a founder effect a small group leaves a population and starts a new one elsewhere. In a bottleneck an existing population is drastically reduced and then recovers. Both leave a population with reduced variation and altered allele frequencies.

What is the difference between genetic drift and natural selection?

Natural selection changes allele frequencies according to differences in fitness and produces adaptation. Genetic drift changes them by chance, regardless of fitness, and does not produce adaptation.

What is gene flow?

Gene flow is the transfer of alleles from one population to another through migrants who reproduce in the new population. It reduces genetic differences between populations and increases variation within them.

What is the difference between gene flow and genetic drift?

Gene flow makes populations more alike and adds variation within each. Genetic drift makes populations less alike and removes variation from each. The two work in opposite directions.

What is a balanced polymorphism?

A balanced polymorphism is the stable maintenance of two or more alleles in a population by selection, most often because the heterozygote is fitter than either homozygote. The sickle-cell trait in malarial regions is the standard example.

What is mutation-selection balance?

It is the state in which a harmful allele stays at a low, constant frequency because new copies arising by mutation are matched by copies removed by selection. Achondroplasia is an example.

What is a genetic isolate?

A genetic isolate is a population descended from a small number of founders that has remained separate, geographically or culturally, for many generations. The Finns, the Old Order Amish and the Hutterites are examples.

What is admixture?

Admixture is the formation of a population through interbreeding between two or more previously separate populations. The share of ancestry from each is the admixture proportion.

What is the difference between inbreeding and assortative mating?

Inbreeding is mating between relatives and raises homozygosity at all loci. Assortative mating is mating between people who are alike in some trait and affects only the loci for that trait.

What is the neutral theory of molecular evolution?

Proposed by Motoo Kimura in 1968, it holds that most variation and change at the level of DNA and protein sequence is selectively neutral and is governed by mutation and genetic drift, not by natural selection.

What is effective population size?

Effective population size is the size of an ideal population that would undergo the same amount of genetic drift as the real population. It is usually much smaller than the actual number of people.

What are transitions and transversions?

A transition replaces a purine with the other purine or a pyrimidine with the other pyrimidine. A transversion replaces a purine with a pyrimidine or the reverse. There are four possible transitions and eight possible transversions.