14 Gene flow and admixture genetics

Tabitha Panmei

Content

1.    Introduction

a)  Gene Flow

b)  Admixture genetic

2.  The impact Evolutionary gene flow

a) New Alleles

b) Genetic Differences between Populations

3.  Gene Flow Model

a)  Island Model

b)  Two- Way Gene Flow

c)    Kin- structured Migration

4.    Methods of Estimating Admixture Proportions

a) Method from frequencies of a single allele

b) Least square estimates from frequencies of multiple alleles

c) Maximum likelihood estimate from multiple alleles-

d) Admixture estimates based on genetic distances-

e) Method based on gene identity-

5.    Case studies of population admixture

a) Peopling of the new world

b) origin of Irish Travelers

c) Admixture in African-American

Learning outcome

• After seeing reading module you would know how gene flow occurs in human population.
• After having read this module, how would you respond to the question? If humans originated from same place and from one population?

1.    Introduction

a) Gene Flow

Interaction between human groups also has genetic implications; the movement of genetic material from one population to another can cause changes in allele frequencies. On other hand, gene flow can be seen as the evolutionary glue holding populations in a species together, and reduction or elimination of gene flow is necessary to initiate the process of speciation.

Gene flow also called migration – is any movement of individuals, and/or the genetic material they carry, from one population to another. Gene flow includes lots of different kinds of events, such as pollen being blown to a new destination or people moving to new cities or countries. In population genetics, gene flow is the transfer of alleles or gene from one population to another. Migration into or out of a population may be responsible for a marked change in allele frequencies (the proportion of members carrying a particular variant of a gene). Immigration may also result in the addition of new genetic variants to the established gene pool of a particular species or population.

Fig1: Gene flow is the transfer of alleles from one population to another population through immigration of individuals. In this example, one of the birds from population A immigrates to population B, which has fewer of the dominant alleles, and through mating incorporate its alleles into the other population.(source: en-wikipedia.org/wiki/Gene-flow)

b) Admixture genetics

The Neighboring populations frequently exchange individuals that contribute to ongoing process of bidirectional gene flow between them. It occurs when individuals from two or more previously separated populations begin interbreeding. Admixture gene flow results in the introduction of new genetic lineages into a population. It is known to slow local adaptation by introducing foreign, un-adapted genotype. It also prevents speciation by homogenizing population. Here in terms of Anthropology, many populations evolved from genetic admixture caused by major migrations during the entire evolutionary history of mankind. The admixed individuals, therefore, show a genetic characteristics commonly found in both parental populations. When the contributing parental populations are genetically very dissimilar, the admixed or hybrid population generally resembles to each of the parental ones in some respect. In fact most often their genetic constitution is somewhere in between those of the contributing parental populations. In describing the population structure of admixed populations, therefore, it is important to identify the mixing elements and the proportions of such mixture. Quantitative assessment of admixture is generally made through the estimation of admixture proportions. When a hybrid population consists of genes from p parental groups, the proportional contributions of these ancestral groups in the total gene pool of the hybrid population are defined as admixture proportions.

When the time depth of admixture is known, these proportional contributions may be translated into rates, with some additional assumptions, yielding estimates of admixture rates. While for anthropological description of hybrid groups, it is enough to know the admixture proportions, for population genetic considerations, a translation of these estimates into rates is necessary in order to study the consequence of migration on the changes of gene frequencies. Therefore, it is important to recognize the difference of the concepts of admixture proportions and migration rate. Sometimes, admixture proportions are also called accumulated admixture levels. While the concepts of admixture proportions and admixture rate generally apply to the population as a whole, it is important to remember that all members of a hybrid population do not have identical contributions from each of the parental groups.

2. The impact of Evolutionary gene flow

Here, Relethford (2012) has given some example of impact of evolutionary gene flow:

a) New Alleles-

The way of new allele to enter in a new population is through mutation, drift and selection. It can make increase or decrease the frequency of a new mutation. Mutation is the ultimate source of all new alleles. Gene flow allows the spread of introducing new mutants through a species, subject in each population to the further effects of drift and selection.

b) Genetic Differences between Populations-

The main impact of gene flow is to reduce genetic differences between populations. Gene flow is an analogous to mixing populations. We can imagine with an example of mixing cans, two gallon cans of paint, one with red paint and another with white paint. Take a cup of paint from the red cans and mix into the white cans at the same time take a cup of white paint and mix it into red cans. After mixing, the cans of red paint are slightly lighter and the cans of white paints are slightly pinker. If you repeat the mixing, the color of paint in the two cans will become increasingly similar. After enough cups of paint have been swapped and mixed, you will see two identical cans of pink paint.

We can picture how the gene flow in an analogous manner where the alleles of two or more populations are mixed together like the above example of cans. Although alleles are not paint, and do not actually merge together, the point here is the mixing of gene pools can alter the allele frequencies. As an example (taken from Re, imagine two populations (A and B), where the frequency of a given allele is p = 1.0 in population A and p = 0.0 in population B. Now, imagine 5% of the individuals in population A move into population B and start reproduce, while 5% of their genes are shown. This means that 95% of the individuals in population A remain in population A. The allele frequency in population A generation later is made up 5% from population B with an allele frequency of p = 0.0. This gives the new allele frequency in population A of

(0.95) (1.0) + (0.05) (0.0) = 0.95

At the same time, we can figure it out allele frequency in population B a generation later by noting that it will consist of 5% from population A with an allele frequency of p = 1.0 and 95% from population B with an allele frequency of p = 0.0,

(0.05) (1.0) + (0.95) (0.0) = 0.05

Gene flow in population A and B have changed the allele frequency from 1.0 and 0.0 to 0.95 and 0.05. They are still quite different, but they were initially closer. Over time, gene flow will make the two populations increasing similar. To figure out the allele frequencies in the next generation, we use the same mixing proportions (95% and 5%) and use the new allele frequencies for populations A and B (p

=  0.95 and p = 0.05). Thus, the allele frequency in population A after two generations of gene flow is (0.95) (0.95) + (0.05) (0.05) = 0.905

And allele frequency in population B is (0.05) (0.95) + (0.95) (0.5) = 0.095

If we see the third generation, we can simply use these new allele frequencies with the same amo unt of mixing to get allele frequencies of

(0.95) (0.0905) + (0.05) (0.095) = 0.8645

For populations A and B.

(0.05) (0.905) + (0.95) (0.095) = 0.1355

We can repeat the same process many times from one generation to generation for seeing the long-term effect of gene flow.

3. Gene Flow model

The previous treatment of evolutionary forces, we can consider gene flow by itself to start with and then add complexity by examining the interaction with other evolutionary forces (Relethford, 2012). Some of the model which shows how gene flow works is:

a)  Island Model –

The simplest example to start with understanding how gene flow works is to examine the case of one-way migration as shown in the island model. Imagine an island that receives a certain amount of migration occurs from the island to the mainland. In this way, we can see the effect of gene flow from the mainland has on allele frequencies of the island.

b)   Two- Way Gene Flow-

The island model focuses on gene flow in one direction, and allele frequency does not change in the source population. This model fits some cases, a model that allows gene flow in two directions is more applicable to many situations.

c) Kin- structured Migration-

The two-way gene flow show clearly that gene flow acts to make populations more similar to each other over time and the higher the rate of gene flow, the more rapidly this convergence occurs. Gene flow is most often considered a homogenizing force that reduces the genetic difference between populations. This is technically correct only if we make the hitherto unstated assumption that the individuals that migrate and reproduce are a random sample of the source population. This may not always be the case. In some situations, the migrants may be related. One way that migrants can be related occurs in some small-scale human societies when part of a population splits off and then fuses with another population. There are other examples of entire families moving into a new population. When the migrants are related, we call this Kin- structured migration.

4. Methods of Estimating Admixture Proportions

The history of admixture studies is at least half a century old, and consequently a wide variety of methods of estimating admixture proportions have been proposed, utilizing data of various kinds. Nevertheless, it must be mentioned that there are three critical assumptions inherent in all methods of estimation that must be verified before they are used. It might be true that the different methods are affected differently from violation of these assumptions, but at present no consensus exists regarding superiority of any particular method over another. Some of the methods given by Chakraborty et al (1986) quoted from different authors are:

a)  Method from frequencies of a single allele-

Bernstein (1931) was the first to use allele frequency data in hybrid a nd parental populations to estimate the proportional contribution of the ancestral stocks in a hybrid population. In principle, if p1,p 2….pk denote the frequencies of a specific allele in k populations, and these populations contribute in m1,m2,…mk fractions (0≤ mi≤ 1; ∑mi = 1) in the formation of a hybrid population, the expected frequency of that allele in the hybrid population will be given by

Ph=∑i=1k mipi

b)  Least square estimates from frequencies of multiple alleles-

Bernstein’s method has another disadvantage, namely, it is limited to admixed populations derived from only two ancestral populations. In order to deal with populations of multiparental origin, and to obtain estimates from multi allelic loci, Roberts and Hiorns (1962, 1965) and Elston (1971) proposed a least square approach to estimate the admixture components of all contributing populations that constitute the gene pool of an admixed group. Their method essentially use the basic principles of the Bernstein equation, on the supposition that admixture affects all loci (or all alleles) equally and simultaneously. The resulting estimation equations which express each allele frequency in the admixed population as linear combinations of respective allele frequencies in the ancestral populations provide the same constants.

c)   Maximum likelihood estimate from multiple alleles-

The first attempt to obtain a maximum likelihood solution of admixture components is by Krieger et al.(1965), where they proposed that allele frequencies in the parental populations are known without error, but a sample of phenotype (or genotype) distribution from the hybrid population is drawn following multinomial sampling. Assuming that the hybrid population is at Hardy-Weinberg equilibrium, the expected allele frequency in the admixed population is obtained is Bernstein equation (equation 1). The phenotype (or genotype) probabilities can then be represented as functions is known allele frequency in parental population and unknown admixture components. Writing the likelihood function as the multinomial probability for the sample of phenotype distributions, maximization of the log- likelihood function can be done by the Newton Raphson method.

d)  Admixture estimates based on genetic distances-

Pollitzer (1964) was the first to derive estimates of admixture proportions based on genetic distances between the hybrid and parental populations. He noted that the contributions of the parental stocks to a hybrid population should be inversely proportion to squares of the distances of the parents from the hybrid. While intuitively it is clear that with increasing gene flow genetic distances should decrease, the exact relationship need not be an inverse function, particularly with the choice of distance measures used by Pollitzer (1964).

e)   Method based on gene identity-

The above mention problem may be circumvented if one considers suitable measures of genetic similarity, instead of genetic distance. For example, if genetic similarity is defined by gene identity (probability that two genes chosen at random from one or more populations are identicle), it can be expressed as linear functions of admixture proportions (Nei and Feldman, 1972).

5.      Case studies of population admixture

a)      Peopling of the new world-

In 1492 Europeans discovered Columbus’s voyages which led the first of the New World. His plan was to circumnavigate the world in order to find a quicker route to parts of Asia which referred as “Indies”. He made the mistake that he had arrived in the Indies because of the local people in the new world and known origin of the native peoples of the Americas. His suggestions included the ideas that Native Americans were a lost tribe of Israel, voyagers from ancient Egypt, or survivors from Atlantis (Crawford 1998). A number of early people recognized that northeastern Asia is the origin, as the Asian and North American continents are close together in the arctic, separated by the Bering Strait. Due to the explanation of migration, long favored by archeologists, they said humans in Siberia were able to move across the Bering Strait during glacial times; during an ice age, the sea level drops, exposing the land that connects the two continents. Human hunters following animal herds would make them crossed over this land bridge. After entering the Americas, due to the massive glaciers these nomads would have been stopped by, except for times during which two glaciers had receded enough for humans entered the New World during a time when the land bridge and ice- free corridor were open, roughly 12,000 years ago. Some of the evidence of earlier occupation has led to this view being questioned, and archeologists have suggested that early migrants used boats to move into New World (Nemecek 2000), and some may have travelled southward along the western coast of North America (Dalton 2003). The increasing evidence for early occupation has increased, with a number of sites suggesting dates as far back as 15,000 years (Goebel et al. 2008; Waters et al. 2011). Due to the regardless of time or routes of migration, first Americans came from northeastern Asia is incontrovertible. After studying gene marker a genetic similarity is seen in a variety of physical and genetic measures. Analysis of genetic distances is based on red and white blood cell markers which shows Native American populations are more genetically similar to East Asian populations than to populations elsewhere in the world, such as Europe, Africa, or Australia. The closeness level of genetic distance to Native American populations is with population of northeastern arctic (Cavalli-Sforza et al. 1994; Crawford 1998).

b)  Origin of Irish Travelers-

In Europe, there are a small number of nomadic groups live together, including the central and eastern Europe. One of these itinerant groups is the Irish Travelers, who make up a very small percentage (< 1) of the population of Ireland. They moves around the country side performing odd jobs, seasonal labor, and scavenging scrap metal, among other activities (Gmelch 1977). They have several ideas about the ancestral origin of the Irish Travelers. Some of the hypotheses focus on the idea that the Travelers are the descendants of Irish who were displaced from their land, becoming an isolated social group over time. Another idea is that they represent a mixture of Irish and Romany gypsies. The difference between two sets of ideas can be tested using genetic data. Crawford and Gmelch (1974) computed genetic distances between a sample of Irish Travelers and a number of European and Asian populations based on red blood cell genetic markers. They find out the Travelers were most similar to Irish populations, and show different from other populations, including several gypsy. They finalize with the genetic data which supports the hypothesis of an Irish origin for the Irish Travelers. Other analyses of the same data using different comparative samples find the same result (Croke et al. 2000; North et al. 2000). The gypsy lifestyle is coincidental with the culture but does not reflect ancestry. It is the often case with human populations, culture is independent of genetics. Genetic drift has had a little important effect on genetic variation in Traveler population. The small size of the Traveler population and the high variance in fertility (Crawford and Gmelch 1974) suggest a relatively lo w effective population size, which would increase of drift. Genetic drift suggested from studies of metabolic disorder known as transferase- deficient galactosemia showing much higher frequencies among the Irish Travelers than other the Travelers were due to a specific mutation known as Q188R, which also accounted for 89% of mutant alleles for the cases among the non-Travelers. When Screening of the overall populations shows the allele frequency of the Q188R mutation is much higher amo ng the Travelers (0.046) than the non-Travelers (0.005). Due to the genetic drift, mutation arose in Ireland and attained an elevated frequency among the Travelers. Some of the result shows differences might be due to initial founder effect and due to continued genetic drift in generations.

c)   Admixture in African -American-

During Colonial time in United States, hundreds and thousands of Africans were enslaved and brought forcibly to the as part of the slave trade. Starting from 1619, the slave trade grew and the important of enslaved Africans was widespread, peaking at the end of the eighteenth centuries, there has been gene flow occurred before the prohibition of slavery, generally when European man would mate with from mattings between European- Americans and African-Americans following the relaxation of social barriers to interracial marriage. European gene were flow into African American, this is an example of the process of admixture as described, genetic marker data can be used to estimate the accumulated European ancestry in African- Americans. Some studies have used the simple model of two parental populations; some looked more complex models and take into account possible admixture from Native American sources. The earliest studies find out no single answer to the question of how European ancestry exists in African- Americans. Genetic history is not the same in all population studies. The variation in European ancestry is shown clearly by a comprehensive study of African-American genetics conducted by Esteban Parra and colleagues (Parra et al. 1998). Here, genetic markers examined from nine loci that exhibited large differences between Europeans and Africans, and estimated admixture proportions in 10 different African- American populations in the United States. They find the amount of accumulated European ancestry ranged is from 12% in Charleston, South Carolina to 23% in New Orleans, Louisiana. These estimates were based on autosomal genetic markers. Parra et al. (1998) also examined admixture estimates based on mitochondrial and Y-chromosome DNA markers, which allow looking at the different evolutionary histories of the female and male lines. The mitochondrial DNA analysis showed European ancestry ranging from 0% in Detroit, Michigan to 15% in Baltimore, Maryland. The estimates from Y-chromosome DNA markers range from 9% in Houston, Texas to 47% in New Orleans. More revealing is the male line than in the female line. These results suggested over the past few centuries have been more European genes coming from the mating patterns of European-American females with African – American male. In proslavery times the majority of interracial mating’s were probably betwee n a male European descent and with enslaved female of African descent. This pattern appears to be reflected in the mitochondrial and Y-chromosome DNA analyses. Since last 40 years, there have been more marriages between a black husband and a white wife than 1990s. This was the recent demographic shift result increase in the maternal component of European ancestry in African- Americans, but it has not noticeable effect on the genetic history of the past. This estimation is based on the genetic makeup of an entire population, and the admixture proportions of a population which are not necessarily apply to every person in that population. Each person has his or her own unique way, genetic history, and our population estimates are simply statistical aggregates of these histories. An estimation of 15% European ancestry for a sample does not mean that every person in that population has 15% European ancestry. An appropriate example of individual variation in ancestry is study of European ancestry in several African-American populations in South Carolina Parra et al.’s (2001). They estimate admixture for individuals and for the entire population. The estimate for Columbia as a whole was 18% European ancestry, but there was considerable variation in individual ancestry; the majority of the individuals had less than 10% European ancestry, while roughly 7% had more than 50% European ancestry. The more isolated cultural Gullah people of South Carolina, over 80% of them is less than 10% European ancestry, and no one has more than 50% European ancestry (Relethford, 2012).

Summary

• Gene flow is happen in any movement of individuals, and/or the genetic material they carry, from one population to another. Gene flow includes lots of different kinds of events, such as pollen being blown to a new destination or people moving to new cities or countries.
• Immigration also results in the addition of new genetic variants to the established gene pool of a particular species or population.
• Admixture results in the introduction of new genetic lineages into a population. It has been known to slow local adaptation by introducing foreign, unadapted genotype s.
• In terms of Anthropology, most of the populations evolved from genetic admixture caused by major migrations during the entire evolutionary history of mankind.
• The admixed individual, have genetic characteristics commonly found in both parental populatio ns. When the contributing parental populations are genetically very dissimilar, the admixed population generally resembles to each of the parental ones in some respect.
• The only way that we have seen a new allele enter a population is through mutation, drift and selection can increase or decrease the frequency of a new mutation, but they cannot bring about a new allele.
• Gene flow allows the spread of new mutants throughout a species, subject in each population to the further effects of drift and selection.
• The main impact of gene flow is to reduce genetic differences between populations.
• We can picture gene flow in an analogous manner where the alleles of two or more populations are mixed together.
• The basic effect of gene flow to reduce genetic differences between populations, we can examine several different models of gene flow in more specific detail.
• The simplest place to start with understanding how gene flow works is to examine the case of one -way migration as shown in the island model.
• A simple model of two- way gene flow where the rate of migration is the same in both directions.
• There are other examples of entire families moving into a new population. When the migrants are related, we call this Kin- structured migration.
• It is true that the different methods are affected differently from violation of these assumptions, but at present no consensus exists regarding superiority of any particular method over another.
• Some of the case studies of population admixture have been study. They are: The peopling o f the new world, the origin of the Irish Travelers and Admixture in African-American which give a result of how it occurred admixture in human population through gene flows?

References

Suggesting Books

• John H. Relethford., (2012): Human population genetics
• Kailash c. Malhotra., (1988): Statistical methods in human population genetics
• Mark Jobling., Edward H., Matthew.H, Toomass. K, Chris.T, (2014): Human Evolutionary Genetics