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MSU / Biological Sciences / BIO 4143 / What are the ways of testing gene flow?

What are the ways of testing gene flow?

What are the ways of testing gene flow?

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School: Mississippi State University
Department: Biological Sciences
Course: Population Genetics
Professor: Brian counterman
Term: Fall 2016
Tags:
Cost: 50
Name: Questions, answers and sum of main ideas for Test 2 PopGen
Description: This guide includes more than 50 main questions including maths, graphs, tables, theoretical questions. Detailed answers are given after all. Altogether includes almost everything covered till Star method of gene flow
Uploaded: 10/04/2016
19 Pages 134 Views 5 Unlocks
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STUDY GUIDE – TEST 2 – POPULATION GENETICS 


What are the ways of testing gene flow?



The following questions are to test your knowledge for the test. The test is really long; you will write a lot on the  test! Basically, you have some questions involving basic maths and concepts, interpretative graphs and  definitions. I tried to point out to questions in which Dr Counterman said in class he would probably ask about.  In the same way, the questions involve more than 90% of this second block, so if you put all together, the answers  will be a summary of everything he said in class. Answers at the end of all questions.  

There are more than 50 main questions!

Good luck!  

1. Who was the closest extinct lineage from humans? And the extant? Give some evidences of both.  2. Give two examples of non-genetic evidence that suggested mixing between humans and Neanderthals.  


Do different genomic regions give different divergent time?



3. Give an example of non-genetic evidence that suggested that mixing did not occurred between AMH and  Neanderthals.  

4. What are the hypothesis about why Neanderthals were extinct?  If you want to learn more check out How to find standard deviation?

5. What earlier studies involving genetic data concluded about AMH and Neanderthals? What type of genetic  material was used?  

6. What this graph tell us about? What is that measuring?  

We also discuss several other topics like What is the pan asian segment?

7. What are the advantages of using mitochondrial DNA?


Who was the closest extinct lineage from humans?



8. What was the sample used by Green et al (2010)?  

9. What made Green et al (2010) study unique?  

10. How Green et al (2010) reduced their contamination and genetic bias analysis?  

11. Why Green et al (2010) avoid GpC island during genetic analysis?

12. Where Neanderthals were found?  

13. How Green et al (2010) showed that the 3 bones from Croatia, found together at same cave, were from  different individuals?  Don't forget about the age old question of Who accepted black recruits after lord dunmore’s proclamation offered freedom to slaves who fought for the british?

14. Define population divergence time. Which results Green et al (2010) found related to population  divergence time?

15. What was the divergence time (in years) estimated by Green et al (2010) for AMH and Neanderthals by  analyzing autosomal chromosomes?  

16. What were the main results that Green et al (2010) obtained?  

17. How much of human genome Green et al (2010) estimated to be unique to humans? How this estimation  was obtained?  

18. Green et al (2010) built two hypotheses to test if Neanderthals were closer related to Non-Africans than  to Africans. What were these hypotheses? Which method they used to test it?  

19. What is gene flow? How it can be detected?  

20. What were the main conclusion Green et al (2010) had about gene flow?  

21. When and where mixing occurred based on Green et al (2010) suggestions? Did mixing between AMH  and Neanderthals occurred before or after AMH expansion?  

22. How much of non-African genomes has Neanderthal ancestry?  

23. How NJ tree can be build using cranial size? Is that useful?  If you want to learn more check out How many tv households are tuned into this particular show?

24. Do different genomic regions give different divergent time? How so?

25. What was the sample used by Burbano et al (2010)?  

26. What Burbano et al (2010) were trying to answer? What were the goals?

27. How different were the sample analysis from Green et al (2010) to Burbano et al (2010)?  28. What were main results from Burbano et al (2010)?  

29. How much of the genome did Burbano et al (2010) estimate that is unique from humans? Does that agree  with Green et al (2010)?  

30. How many genes Burbano et al(2010) identified human derived substitutions? If you want to learn more check out What are the energy changes in chemical reactions?

31. What are the non-genetic data that mixing between AMH and Denisovan occurred?  32. Analyzing the following sequences from different individuals, answer the questions.

 1 2 3 4 5 6 7 8 9 10 >> Position on the sequence

African ……...…C.C.T.A.G.T.A.T.G.G……….

European……….C.T.T.A.G.T.A.T.A.G……….

Asian... ………...C.T.T.A.G.T.A.T.A.G……….

Neanderthal ……T.T.G.T.C.G.C.G.A.G……….

Chimpanzee ……T.C.T.A.C.T.A.T.A.G……….

a) Which nucleotides can be classified as having human derived alleles? Give their positions. b) Which SNPs can be classified as Neanderthal derived alleles? Give their positions. c) Which SNPs could explain a gene flow between Human and Neanderthal? Give their positions.

33. What was the main objective of Meyer et al (2012)?

34. What was the sample used by Meyer et al (2012)?

35. Which type of alterations can be found in an ancient DNA?  

36. What were the results obtained by Meyer et al (2012)?  

37. What is enhanced D statistics? How it differs from what Green et al (2010) did? If you want to learn more check out What happened to religion in bioethics?

38. What were the evidences that Meyer et al (2012) found that mixing between AMH and Denisovan  occurred?  

39. What is the human population that most presents archaic human alleles showed by Meyers et al (2012)?  What would be archaic human alleles?  

40. What was the divergence time estimated by Meyers et al (2012) for AMH and denisovans?  41. What is F4 statistics? What is the difference between this method and Patterson’s D statistic?  

42. Draw the main types of complex demographic model. Who tested it? How it was tested and which model  is more likely to be true?  

43. Define introgression.  

44. What are the ways of testing gene flow?  

45. What is ABBA-BABA test? Who created it?  

46. Given the following sequences, draw what would be more likely to be the tree, ABBA-BABA pattern.  Does this tree suggest migration/ gene flow?

Lineage 1

A

G

C

G

A

T

G

G

A

Lineage 2

A

T

T

G

C

G

C

T

T

Lineage 3

A

T

C

T

A

G

C

T

T

Lineage 4

A

G

T

T

C

T

G

A

C

47. What means Patterson’s D test is D=0? And when it is different from zero?  

48. Define Rind and Rpop. Given the following genome from 10 individuals from each population, give Rind  and Rpop and what their numbers represents. What each line represents?

Europeans East Asians

49. The following table show alleles from different individuals which has 5 SNPS that were characterized as  being Neanderthal-derived alleles. By using Patterson’s D method, give the answers.  Location of SNP 1 2 3 4 5 

African C A C T T 

European T C C A G

Asian T A T A T 

Neanderthal T C T A G

Chimpanzee C A C T T 

a. Is there possible to say that it has an excess of Neanderthal derived alleles in AMH from Europe when  comparing with Africa?  

b. In the same way, is there an excess of Neanderthal derived alleles in AMH from African when  comparing with Europe?  

c. How much Neanderthal derived alleles African and European share?  

50. What was new about Prufer et al (2014)?

51. Which demographic models Prufer et al (2014) tested? Which model were more likely to be true?  52. Why mitochondrial DNA analysis got a different structural NJ tree than when analyzing nuclear genome?

STUDY GUIDE – TEST 2 – POPULATION GENETICS 

The following questions are to test your knowledge for the test. The test is really long; you will write a lot on the  test! Basically, you have some questions involving basic maths and concepts, interpretative graphs and  definitions. I tried to point out to questions in which Dr Counterman said in class he would probably ask about.  In the same way, the questions involve more than 90% of this second block, so if you put all together, the answers  will be a summary of everything he said in class. Answers at the end of all questions.  

Good luck!  

1. Who was the closest extinct lineage from humans? And the extant? Give some evidences of both.  Neanderthals are the closest extinct lineage from humans, while the great apes are the closest extant.  Evidences that Neanderthals are the closest lineage from humans include (1) similarities in fossil  morphology in general (2) time frame period giving potential for mixing, lived at same place at same time  (2) similar cultural characteristics (3) genetic pattern of variation with relatively few non-genetic and  genetic differences. Evidences that great Apes are the closest extant lineage from humans include: (1)  similar vertebra structure, stature, hands, feet, skull, immune system (2) protein similarities by  Zuckerkandl & Pauling (3) DNA hybridization results (4) Chen & Li, 2001 and Patterson et al (2006).  

2. Give two examples of non-genetic evidence that suggested mixing between humans and Neanderthals.  -Geographic distribution of fossils: some regions at Euroasia of Neanderthals’ fossils and anatomic  modern humans (AMH) were found to live together in the same period of time. So once they shared same  environment at same time frame, mixing could have occurred.  

-Cultural similarities: both populations shared same cultural aspects such as burring dead bodies, having  a kind of religion, control of fire, complex language. But most important evidence is the tools.  Neanderthals and non-African population shared tools that were relatively close to each other comparing  with tools used at same time from African populations. It suggested that AMH and Neanderthals on  Euroasia had, at least, been in contact and exchanged information.  

3. Give an example of non-genetic evidence that suggested that mixing did not occurred between AMH and  Neanderthals.  

Mainly studies involving cranial size and bone structure. Neanderthals have specific anatomical traits such  as, they are stockier, shorter, stronger limbs than AMH. Moreover, they have a bell shaped rib cage, larger  nasal sinuses and lack of chin. The most important non-genetic evidence was given by Harvarti et al  (2004).  

-Havarti et al (2004) studied the cranial size of AMH and Neanderthals. Although, the cranial aspect was  similar between both, when analyzing measurements of cranial size in different perspectives using  computer software, a significant difference was found. So they showed that significant variation in cranial  size suggested no mixing between them. Because if mixing had occurred, Neanderthals should be more  similar to the species that they historical and geographical overlapped than to other species they did not  overlapped. Havarti et al (2004) showed that Neanderthals have equal number of differences on cranial  size when compared with populations they overlapped in time/space and populations that they did not  overlap.  

- By fossil measurements, a first family tree was built. This neighbor-joining tree put Neanderthals close  to Homo sapiens species, but as different species! Different species do not mix or do not produce fertile  generations.  

4. What are the hypothesis about why Neanderthals were extinct?  

Two theories are involved (1) continuity theory (2) replacement theory.

-Continuity theory says that mixing between AMH and Neanderthals happened in the past and the turned  to be the same specie today. So it is about the transformation of archaic into modern form within lineages.  -Replacement theory: mainly no mixing between AMH and Neanderthals happened. Over time expansion  of AMH and selection ended up to replacing Neanderthals.  

5. What earlier studies involving genetic data concluded about AMH and Neanderthals? What type of genetic  material was used?  

The earlier genetic data involved the use of mitochondrial DNA from Neanderthals’ bones and other  individuals including 16 chimpanzees and 994 humans from different parts of the globe (Europe, Africa,  Asia, Australia). The study performed by Krings et al (1997), used sequencing of the hypervariable region  (HVI) on mitochondria to count the differences between and within populations using pairwise method.  From the results of pairwise method, they plot a graph which showed no overlap between differences in  Human-Human and Human-Neanderthal results. It was an evidence that mixing had not occurred between  AMH and Neanderthals. If mixing had occurred, the pairwise difference in Human-human would be more  similar to Human-Neanderthal, so overlap on graph would occur.  

6. What this graph tell us about? What is that measuring?  

The graph gives the number of differences on mitochondrial DNA between human populations and other  populations. So mainly within human populations, variation on mitochondrial DNA are within 0-15, while  differences between human and Neanderthal populations are between 20-30 and human-chimpanzee more  than 50 differences. It tells us that mixing between human and Neanderthal populations might not have  happened based only by mitochondrial DNA.  

7. What are the advantages of using mitochondrial DNA?

It is easier to collect from ancient bones, have more amount of mitochondrial DNA in a cell than nuclear  DNA. It is low cost. It fits better at molecular clock assumptions. However, it has lower genetic variability  when compared with nuclear DNA as we could observe at Prufer et al(2014).  

8. What was the sample used by Green et al (2010)?  

Their study included (1) 3 Neanderthal bones, Vi33.16, Vi33.25 and Vi33.26, from individuals found at  same cave bear in Croatia (2) 5 human samples which included individuals from South Africa (San), West  Africa (Yoruba), New Guinean (Papua), China (Han) and Western Europe (French).  

9. What made Green et al (2010) study unique?

They used whole genome sequencing, including 4Gb, and new methods that reduced contamination of  samples and included next generation sequencing.  

10. How Green et al (2010) reduced their contamination and genetic bias analysis?  a. They got bones from Neanderthals that were remained yielded, low human contact.  b. Used 3 approaches to detect percentage of contamination including (1) mitochondrial DNA,  

comparing how close human and Neanderthal were on some specific regions of DNA (2) Y  chromosome, so all bones were females so if Y chromosome was present, it was contamination (3)  nuclear DNA, used derived alleles from humans that are not seen on Neanderthals and chimps.  

11. Why Green et al (2010) avoid GpC island during genetic analysis?  

Because they are hypermutable regions. They do not evolve in a molecular clock fashion. However,  regions close to GpC island does.  

12. Where Neanderthals were found?  

Mainly Euroasia. No Neanderthals on Africa!  

13. How Green et al (2010) showed that the 3 bones from Croatia, found together at same cave, were from  different individuals?  

To prove that Vi33.16, Vi33.26 and Vi33.25 were from different individuals by analyzing:  a. Mitochondrial DNA: they compared at 10 different sites the mitochondrial DNA sequences from these  bones and found that Vi33.16 and Vi33.26 were from different individuals once they had different  mitochondrial sequences at these sites. However, Vi33.26 and Vi33.25 were not different enough to  conclude it.

b. Nuclear DNA: used mainly to determine if Vi33.26 and Vi33.25 were same individual. They  sequenced both DNA from the bones and also sequenced twice same both. Concluded that within same  bone there were few differences when compared between bones, suggesting that each bone belonged  to different individuals.  

14. Define population divergence time. Which results Green et al (2010) found related to population  divergence time?  

Population divergence time is the time when 2 populations last exchanged genes. Same concept as time  of speciation.  

Green et al (2010) calibrated their molecular clock using Orangutan fossil (15-20 mya) and calculated  human-chimp genetic divergence time 5.6-8.3 mya. Then, using Neanderthal and Yoruba samples, they  calculated divergence time 1,087,000- 734,000 years ago, which is τ genome. The τ species between  Neanderthal and Yoruba was estimate to 272,000 – 435,000 years ago. However, comparing other human  populations across the world and Neanderthal, the τ species was estimated to 441,000-684,000 years ago.

15. What was the divergence time (in years) estimated by Green et al (2010) for AMH and Neanderthals by  analyzing autosomal chromosomes?  

NH population divergence time was 272,000-435,000 years ago.  

16. What were the main results that Green et al (2010) obtained?  

a. Derived and shared alleles analysis: the hypothesis was that if non-Africans and Neanderthals had  mixed, they would have more shared alleles. Derived alleles are specific alleles found in a population  due to mutations. They found that humans have ~12.7% of derived alleles, while Neanderthals had 30  times higher mutations which was probably caused by ancient DNA deamination. From derived alleles

in X chromosome, ~12.4% was found to be derived alleles and was within expectations based on  population size (Ne).  

b. Population divergence time: showed that humans and Neanderthals shared genetic variation for long  time and have relatively few non-genetic and genetic differences. So it was hypothesized that it  happened because (1) mixing occurred before initial population split (2) second contact between  human and Neanderthal (3) slow splitting process and/or (4) only some groups happened to mix.  

c. Using D statistic comparing H1, H2, Neanderthal, chimp, which H1 and H2 are two human  populations compared once at time. D statistic for Asian-European populations was -0.53 (almost  zero), so East Asian and European American were equally close to Neanderthal. D statistic for African European was 4.5 (different from zero), so Neanderthals were more similar to Europeans than  Africans. D statistic for African-Asian was 4.81 (different from zero) so Neanderthals were more  similar to East Asians than Africans. So it gave evidence that mixing with Non-African populations  occurred. Same statistic was used to determine when and where gene flow between AMH and  Neanderthal occurred.  

17. How much of human genome Green et al (2010) estimated to be unique to humans? How this estimation  was obtained?  

They estimated that humans have ~12.7% of derived alleles that are unique to humans. This estimation  was based on sequencing, alignments, consensus and counting pairwise differences of DNA between  human and Neanderthals and chimps.  

18. Green et al (2010) built two hypotheses to test if Neanderthals were closer related to Non-Africans than  to Africans. What were these hypotheses? Which method they used to test it?  

-Null hypothesis: no gene flow. If no mixed occurred, Neanderthals would be equally divergent to Non African and African populations.  

-Alternative hypothesis: divergence occurred with gene flow. So if gene flow between human and  Neanderthal populations occurred after the divergence of human population, then Neanderthals would be  less divergent from populations where mixing occurred.  

-Hypotheses were tested by identifying SNPs from random chosen sequences (derived alleles) and  comparing them between different populations (European, East Asian, West African). They also tried to  find fixed alleles from Neanderthals on human populations. Applied D statistics to verify the differences  between populations. D compared the difference in the frequency of Neanderthal fixed alleles between  two human populations. So if no gene flow happened, D =0, which means N-European, N-African, N

Asian have almost similar amount of Neanderthal derived alleles. If gene flow happened, which means  N-European, N-African, N-Asian have different number of derived alleles, D is different from zero.  

19. What is gene flow? How it can be detected?  

Gene flow is the transfer of genomic alleles from one population to another.  

Detection of gene flow: use derived alleles that will characterize a particular population. Derived alleles  can be identified by finding single nucleotide polymorphisms (SNP).  

20. What were the main conclusion Green et al (2010) had about gene flow?  

Genomic evidence of Neanderthals mixing with non-African populations. Europeans and Asians have  more similar levels of gene flow with Neanderthals. So probably mixing occurred after African/ non African split. So mixing likely occurred after migration from Africa but before non-African population  expansion based on geographic distribution, once no fossils of Neanderthal and human overlap in Asia.

21. When and where mixing occurred based on Green et al (2010) suggestions? Did mixing between AMH  and Neanderthals occurred before or after AMH expansion?  

To answers to this question, Green et al (2010) got more samples from human populations around the  world and verified no difference in D within Euroasian or African populations, which means that  populations from both continents showed similar levels of gene flow with other populations from same  continent.  

N-Papuan = N-French = N-Han and N-Yoruba = N-San.  

So it suggested that mixing occurred after migration from Africa to Euroasia and before non-African  population expansion. The fact that no Neanderthal fossils were never found in Asia supports the genetic  data.  

In sum, we have Neanderthal alleles in Asia, but no Neanderthal fossils in Asia.  

Gene flow probably occurred between 50,000-80,000 years ago.  

22. How much of non-African genomes has Neanderthal ancestry?  

Estimate that 1-4% of Euroasian share alleles derived from Neanderthals.  

23. How NJ tree can be build using cranial size? Is that useful?  

It can be built by analyzing differences on measurements. Yes, it is very useful. Many studies use  morphological data to build NJT.  

24. Do different genomic regions give different divergent time? How so?

Yes, some regions divergently more rapidly than others (ex, 16mya versus 4mya).  

25. What was the sample used by Burbano et al (2010)?  

They used one male Neanderthal from El Sidron (~39,000 years ago), 50 human samples, 1 chimp, 1  orangutan.  

26. What Burbano et al (2010) were trying to answer? What were the goals?

Identify how much genetic variation was there within Neanderthals, identify human specific derived  alleles and sequence more Neanderthal genome to verify what they had that we don’t.  

27. How different were the sample analysis from Green et al (2010) to Burbano et al (2010)?  While Green et al (2010) focused on nuclear genome and SNPs, Burbano et al (2010) focused on analyzing  protein sequences and non-synonymous substitutions between human, chimp, orangutan and Neanderthal.  

28. What were main results from Burbano et al (2010)?  

By targeting human non-synonymous substitutions at protein sequences, they found:  a. Neanderthal had ~14,000 amino acid substitutions since split with chimps, from them 88 were found to be fixed in human populations.  

b. 87% shared alleles between Neanderthal and human populations, that were different from chimps,  which means that is very little what make us different from Neanderthals.  

c. 0.8% human derived, which means only 0.8% is what make us different/ unique from Neanderthals.  

29. How much of the genome did Burbano et al (2010) estimate that is unique from humans? Does that agree  with Green et al (2010)?  

Burbano et al (2010) estimated by non-synonymous substitutions that humans have 0.8% of derived  alleles, that makes us unique. This estimation is far from Green et al (2010) that estimated ~12.7%. The

explanation from this difference is that Burbano et al (2010) covered more Neanderthal genome than  Green et al did.  

30. How many genes Burbano et al(2010) identified human derived substitutions?

83 genes had human derived substitutions, only 83 genes from 25,000 genes are unique in humans!

31. What are the non-genetic data that mixing between AMH and Denisovan occurred?  The non-genetic evidence is the geographic distribution of Denisovan and AMH. The only bones found  that belonged to Denisovan were at Denisova cave in Siberia and at same cave AMH and Neanderthal  fossils were found together. The time frame also indicates they lived at same time/location ~41,000 years  ago.  

32. Analyzing the following sequences from different individuals, answer the questions.  

 1 2 3 4 5 6 7 8 9 10 >> Position on the sequence

African ……...…C.C.T.A.G.T.A.T.G.G……….

European……….C.T.T.A.G.T.A.T.A.G……….

Asian... ………...C.T.T.A.G.T.A.T.A.G……….

Neanderthal ……T.T.G.T.C.T.C.T.A.G……….

Chimpanzee ……T.C.T.A.C.T.A.T.A.C……….

a) Which nucleotides can be classified as having human derived alleles?  

Only found in humans are SNPs located at position: 1 and 5.

b) Which SNPs can be classified as Neanderthal derived alleles?  

Only found in Neanderthals: 3,4,7

c) Which SNPs could explain a gene flow between Human and Neanderthal?  

Only present in human and Neanderthal: 2 and 10.

33. What was the main objective of Meyer et al (2012)?

The goals were: (1) test for evidence of Denisovan and Neanderthal admixture with AMH (if allele sharing  happened) (2) test which populations would be close related to Denisovan.  

34. What was the sample used by Meyer et al (2012)?

Data included: (1) 40mg o Denisovan bone, covering 31-fold genome, which means they sequenced the  genome 30 times that included 1.86Gb of regions of genome in which orthologous sequences could be  aligned with Chimps and humans (2) one chimp (3) 11 human genomes from different regions of the  world – Africa (San, Yoruba, Mbut, Mandenka, Denka), Europe (French, Sardinian), Asia (Han, Dai,  Papuan) and South America (Katariana).  

35. Which type of alterations can be found in an ancient DNA?  

Ancient DNA often lose G residues due to depurination. Moreover, cytosine often changes to thymine in  a process called deamination, or vice-versa. Both occurs at same frequencies.

36. What were the results obtained by Meyer et al (2012)?  

a. By pairwise differences, they calculated genetic divergence time between HD ~800,000 years ago and  population divergence time ~170-700,000 years ago. Remember: population divergence should be  more recent than genetic divergence.  

b. By calculation of number of substitutions, they estimated age of fossil in 74-82,000 years, which were  similar with arqueologycal evidence.

c. 12.2-12.5% of genetic differences between humans and Denisovan  

d. Build a NJ tree in which Papuans had 6% derived alleles from Denisovan. So, 94% of genome in all  populations have same pattern.  

e. Test gene flow using enhanced D statistics, where they compared African, Non-African populations  with Denisovan. Observed that Denisovan share more alleles with East Asia and South America than  Europeans, although it does not appear to be due to gene flow. Neanderthal ancestry is 24% lower in  Europe than Eastern Asia, suggesting that 2 independent gene flows happened during history. Papuans  share more autosomic alleles with Denisovan than X-chromosome which could be explained by (1)  gene flow into Papuan ancestors involved primary Denisovan males combined with female migration  (2) selection against hybrid incompability alleles – the rule of X chromosome in which X chromosome  accumulate mutations that are more likely to cause autosomic incompability and suffer selection over  time.  

37. What is enhanced D statistics? How it differs from what Green et al (2010) did?  The enhanced D statistics used by Meyer et al (2012) restricts analysis to alleles that are not present in 35  African genomes and are more likely to be archaic genome origin. It compares outside group (Chimp),  archaic genome (Denisovan) and 2 populations that varied comparing: (a) African and African population  (b) Non-African and Non-African population (c) African and Non-African population. Enhanced D  statistics gives the significant alleles present in a specific population compared to another. Green et al (2010) used the Patterson’s D statistic, which is one of the main tests used to test gene flow.  Just like enhanced D test, you get 4 populations, one of them is to analyze the taxa, which is the outside  group (chimp). Sample wise include extant population and archaic population. It allows to analyze  evolution of 3 lineages.

38. What were the evidences that Meyer et al (2012) found that mixing between AMH and Denisovan  occurred?  

One genomic evidence that suggested mixing was that Papuan populations have ~6% of derived alleles  from Denisovan. Denisovan derived alleles were found to be present in Oceania populations more than  any other populations around the world. Moreover, analyzes of amino acid substitutions showed that some  of these populations had (just few populations) same amino acid substitutions which were mostly realted  with brain functions. The 6% derived alleles were found by building a NJ tree based on similarities on  genomic pattern.  

39. What is the human population that most presents archaic human alleles showed by Meyers et al (2012)?  What would be archaic human alleles?  

Papuans and Oceanians have more Denisovan and Neanderthal derived alleles (archaic genome).  Papuans present ~6% of archaic genome count towards their whole genome.  

40. What was the divergence time estimated by Meyers et al (2012) for AMH and denisovans?  Approximately 800,000 years.  

41. What is F4 statistics? What is the difference between this method and Patterson’s D statistic?  It is a measure of the proportion of Y genome found in X genome. It is like a Patterson’s D but it does not  measure the difference. It gives you the ratio about which population is closest to the archaic genome. So  what you are calculating is alleles that are shared in Denisovan and specific population (ex. French) but  not in another population (ex Yoruba) and the relative amount of X that the first compared population (ex  French) has.

F4 = (Yoruba, Denisovan, French, X), in which Yoruba is the population without archaic genome,  Denisovan is the population with archaic genome, French is the population that shares archaic genome  and X is the population of interest that is receiving the shared genome.  

This method could show the distribution of archaic genome in which Oceanians have more Denisovan  genome and East Asia/ Russians have more Neanderthal genome.  

42. Draw the main types of complex demographic model. Who tested it? How it was tested and which model  is more likely to be true?  

Vernot and Akey (2014) tested a complex demographic model for humans and Neanderthals. Different  from Green et al (2012), they used more Neanderthal genome and by getting genome from different  populations around the world they measured how much archaic genome was found on each population  and each individual from that population. By measuring shared alleles from each individual (Rind) and  from each population (Rpop), they concluded that same amount of archaic genome is present on different  populations. However, when analyzing per individual, East Asia had higher amount. So it was likely that  two pulse model was the truest. But to prove it, they used computer programs and did simulations of  population allele frequencies over time. They simulate two populations at time and included migration  variable. Simulations are based on Fisher’s model.  

At the models, T1 represents the split of archaic population and AMH. If gene flow had happened once  before split, archaic alleles would be equally found on Asian and European populations. However,  individual analysis showed higher archaic alleles on Asians suggesting that two pulse model is more  compatible with what happened.  

Vernot and Akey goes against the theory of Green at al once Green et al said that Europeans and Asians  have same amount of Neanderthal genome and one pulse was more likely to have happened while Vernot  and Akey showed individual differences between the populations that count towards the two pulse theory.  

43. Define introgression. What is adaptive introgression?

Introgression is the transfer of genetic information from one species to another as a result of hybridization  between them and repeated backcrossing. Introgression is what happened between Neanderthals and  AMH, once they got separated (T1 line) and migration happened (hybridization at m1 and m2).  Adaptive introgression is when genetic patterns that were transferred in the past are kept along generations.  One example is the fact that we still keep Neanderthals alleles. It might be in response of genetic selection.  

44. What are the ways of testing gene flow?  

Building NJ tree, Patterson’s D, ABBA-BABA test and Star test.

The first test for gene flow was suggested by Meyers et al (2012) where they built a NJ tree suggesting  gene flow between Denisovans and Papuans.  

45. What is ABBA-BABA test? Who created it?  

Developed by Green et al (2012). It is a really useful method in genetics. It is a test for introgression:  determine if taxa that look alike share similar alleles. This test uses Paterson’s D to analyze from example  if different species of butterflies share same pattern of color due to introgression (gene flow) or because  they just mimic each other as a result of natural selection.  

The method includes sequencing DNA from these different species and counting down their similarities.  Similar patterns of SNPs are registered and then you test the probability of seeing BABA or ABBA pattern.  The tree is build based on which pattern is seeing more often between lineage 1 and 2 and lineage 1 and  3.  

On this test each letter represents a lineage from 1 to 4. BABA occurs when more shared SNPs are  observed between lineage 1 and 3 and between lineage 2 and 4. BABA occurs when more shared SNPs  appears between lineages 1 and 3. Because more similar pattern occurs in separated lineages (1 and 3) on  BABA pattern, it is suggested gene flow between them. ABBA suggest no gene flow and similarities  between lineages occurred due to same common ancestor.  

46. Given the following sequences, draw what would be more likely to be the tree and ABBA-BABA pattern.  Does this tree suggest migration/ gene flow?  

Lineage 1

A

G

C

G

A

T

G

G

A

Lineage 2

A

T

T

G

C

G

C

T

T

Lineage 3

A

T

C

T

A

G

C

T

T

Lineage 4

A

G

T

T

C

T

G

A

C

 

Lineage 1 Lineage 2 Lineage 3 Lineage 4

A B B A

These sequences suggest ABBA Tree. Because there are more ABBA patterns seen than BABA. It suggests no  gene flow occurred between populations 1 and 3 or 1 and 2.  

47. What means Patterson’s D test is D=0? And when it is different from zero?  

Imagine Patterson’s D working as ABBA- BABA test. Once you go through counting which type of  pattern you see more often you can have as result:

ABBA = BABA (same or similar numbers of these patterns) which means D = 0 or is  approximately zero. D=0 means that no gene flow happened or ancestral gene flow happened long time  ago.

ABBA ≠ BABA (it can be either ABBA > BABA or BABA> ABBA) that means that D≠ 0. It  means that it is likely that gene glow happened. Mostly if BABA > ABBA gene flow happened. If ABBA > BABA, the allelic pattern can be due to common ancestor.  

48. Define Rind and Rpop. Given the following genome from 10 individuals from each population, give Rind  and Rpop and what their numbers represents. What each line represents?

Europeans East Asians

R is a genetic ratio test in which you test the average of archaic genome within populations and between  populations. So Rind is the measure of average archaic genome sequence per individual, based on the ratio  between European (population 1) and East Asian (population 2). Rpop is the measure of average genome  in population based on the ratio between Europeans (population 1) and East Asian (population 2).  

Each line represents one individual and each yellow box represents a part of archaic genome (note that  some individuals have 2 archaic genomes on their genome!)

Rpop = (total of individuals with archaic genome in pop1)/ (total of individuals in population1) + (total in  individuals with archaic genome in pop2)/ (total of individuals in population2) = 0.9 Ratio pop 1 = (total of archaic genome in pop1)/ (total of individuals in population1) Ratio pop 2 = (total of archaic genome in pop2)/ (total of individuals in population2) Rind = {(ratio pop1 / ratio pop2) + ratio pop1} + {(ratio pop1 / ratio pop2) + ratio pop2} / 2 Rind = {(0.4 / 0.8) + 0.4} + {(0.4/0.8) + 0.8} = 2.2 / 2 = 1.1

∙ Rind ~1.1 means that every individual in Asia has 10% more archaic genome than an individual from  Europe.  

∙ Rpop ~0.9 which is almost 1, means that both populations appear to have almost the same amount of  archaic genome, which is different from Rind.  

49. The following table show alleles from different individuals which has 5 SNPS that were characterized as  being Neanderthal-derived alleles. By using Patterson’s D method, give the answers.  Location of SNP 1 2 3 4 5 

African C A C T T 

European T C C A G

Asian T A T A T 

Neanderthal T C T A G

Chimpanzee C A C T T 

a. Is there possible to say that it has an excess of Neanderthal derived alleles in AMH from Europe when  comparing with Africa?  

Yes. SNPs at location 1, 2, 4, 5 are likely to be Neanderthal derived allele. So Europeans show 4/5  SNPs from Neanderthal that Africans do not.  

b. In the same way, is there an excess of Neanderthal derived alleles in AMH from African when  comparing with Europe?  

Yes. SNPs at location 1, 3, 4. Asians show 3/5 SNPs from Neanderthals that Africans do not have.  c. How much Neanderthal derived alleles African and European share?  

They share 2/5 Neanderthal derived alleles (SNPs located at position 1 and 4). So there is a similar number of Neanderthal derived alleles in AMH from both populations.  

50. What was new about Prufer et al (2014)?

-they included new Neanderthal and AMH like bones on their research, so more genes available at this  time

-they focus on 25 genes, looking at alleles that were linked together across the chromosome -build two NJ trees, one based on mitochondrial DNA analysis and other based on nuclear genomic  analysis

-they build a new possible model of demographic history once by experimental methods and simulations  of allele frequencies on populations they found out that African populations share more alleles with  Neanderthals when compared with Denisovan. So they concluded that a possible unknown unnamed  population (ghost population) was probably responsible for introgression with Denisovan that made them  up to 8% different from Neanderthal population. From this 8%, around 1.5-2% were migrated to Non

African populations and ~3-6% were migrated to Oceanian/ Papuan populations (two pulse model  occurred after the gene flow between this unknown population and Denisovan).  

-analysis of non-synonymous substitutions, found out 352 fixed alleles on human populations (more fixed  alleles, when comparing with the 260 found by Meyers et al (2012)).  

-used a different test for gene flow called new Star, in which is based on a new parameter, based on linkage  disequilibrium as associated to gene flow.

-so archaic alleles were found in Africa! That’s their unique finding! So suggesting a more complex gene  flow had happened on history of human evolution.  

51. Which demographic models Prufer et al (2014) tested? Which model were more likely to be true?  They tested 3 models: (1) model 1 – neanderthal derived alleles migrating to AMH (20 model 2 – AMH  derived alleles migrating to neanderthal (3) model 3 – unknown ancestral migrating to Denisovan. All of  that because of evidences of more archaic neanderthal shared alleles between African and Neanderthal  than African and Denisovan.  

By simulations methods they compared their observed data with results of each simulation result they obtained. The model 3 were more likely close to what they had as observed data, so it was probably the best fits as demographic model.  

52. Why mitochondrial DNA analysis got a different structural NJ tree than when analyzing nuclear genome? Mitochondrial DNA analysis from Prufer et al (2014) showed low resolution, shorter branches and small  scale box. It is because mtDNA has low mutation rate and lower differences, so it becomes more difficult  to differentiate individuals genetically. At mtDNA tree it had short differences among the Neanderthal  population, so they were practically grouped all together.  

Nuclear DNA is more predisposed to mutations and recombination and more genetic diversity, so branches  get longer and way better defined differences between individuals can be seen. Using nuclear DNA,  Neanderthals could be differentiate better in different lineages, for example.  

PLEASE, CONCERNS, DOUBTS AND SUGGESTIONS FEEL TOTALLY FREE TO  CONTACT ME BY E-MAIL! 

HOPE YOU DO AWESOME ON YOUR TEST! 

mmm687@msstate.edu

STUDY GUIDE – TEST 2 – POPULATION GENETICS 

The following questions are to test your knowledge for the test. The test is really long; you will write a lot on the  test! Basically, you have some questions involving basic maths and concepts, interpretative graphs and  definitions. I tried to point out to questions in which Dr Counterman said in class he would probably ask about.  In the same way, the questions involve more than 90% of this second block, so if you put all together, the answers  will be a summary of everything he said in class. Answers at the end of all questions.  

There are more than 50 main questions!

Good luck!  

1. Who was the closest extinct lineage from humans? And the extant? Give some evidences of both.  2. Give two examples of non-genetic evidence that suggested mixing between humans and Neanderthals.  

3. Give an example of non-genetic evidence that suggested that mixing did not occurred between AMH and  Neanderthals.  

4. What are the hypothesis about why Neanderthals were extinct?  

5. What earlier studies involving genetic data concluded about AMH and Neanderthals? What type of genetic  material was used?  

6. What this graph tell us about? What is that measuring?  

7. What are the advantages of using mitochondrial DNA?

8. What was the sample used by Green et al (2010)?  

9. What made Green et al (2010) study unique?  

10. How Green et al (2010) reduced their contamination and genetic bias analysis?  

11. Why Green et al (2010) avoid GpC island during genetic analysis?

12. Where Neanderthals were found?  

13. How Green et al (2010) showed that the 3 bones from Croatia, found together at same cave, were from  different individuals?  

14. Define population divergence time. Which results Green et al (2010) found related to population  divergence time?

15. What was the divergence time (in years) estimated by Green et al (2010) for AMH and Neanderthals by  analyzing autosomal chromosomes?  

16. What were the main results that Green et al (2010) obtained?  

17. How much of human genome Green et al (2010) estimated to be unique to humans? How this estimation  was obtained?  

18. Green et al (2010) built two hypotheses to test if Neanderthals were closer related to Non-Africans than  to Africans. What were these hypotheses? Which method they used to test it?  

19. What is gene flow? How it can be detected?  

20. What were the main conclusion Green et al (2010) had about gene flow?  

21. When and where mixing occurred based on Green et al (2010) suggestions? Did mixing between AMH  and Neanderthals occurred before or after AMH expansion?  

22. How much of non-African genomes has Neanderthal ancestry?  

23. How NJ tree can be build using cranial size? Is that useful?  

24. Do different genomic regions give different divergent time? How so?

25. What was the sample used by Burbano et al (2010)?  

26. What Burbano et al (2010) were trying to answer? What were the goals?

27. How different were the sample analysis from Green et al (2010) to Burbano et al (2010)?  28. What were main results from Burbano et al (2010)?  

29. How much of the genome did Burbano et al (2010) estimate that is unique from humans? Does that agree  with Green et al (2010)?  

30. How many genes Burbano et al(2010) identified human derived substitutions?

31. What are the non-genetic data that mixing between AMH and Denisovan occurred?  32. Analyzing the following sequences from different individuals, answer the questions.

 1 2 3 4 5 6 7 8 9 10 >> Position on the sequence

African ……...…C.C.T.A.G.T.A.T.G.G……….

European……….C.T.T.A.G.T.A.T.A.G……….

Asian... ………...C.T.T.A.G.T.A.T.A.G……….

Neanderthal ……T.T.G.T.C.G.C.G.A.G……….

Chimpanzee ……T.C.T.A.C.T.A.T.A.G……….

a) Which nucleotides can be classified as having human derived alleles? Give their positions. b) Which SNPs can be classified as Neanderthal derived alleles? Give their positions. c) Which SNPs could explain a gene flow between Human and Neanderthal? Give their positions.

33. What was the main objective of Meyer et al (2012)?

34. What was the sample used by Meyer et al (2012)?

35. Which type of alterations can be found in an ancient DNA?  

36. What were the results obtained by Meyer et al (2012)?  

37. What is enhanced D statistics? How it differs from what Green et al (2010) did?

38. What were the evidences that Meyer et al (2012) found that mixing between AMH and Denisovan  occurred?  

39. What is the human population that most presents archaic human alleles showed by Meyers et al (2012)?  What would be archaic human alleles?  

40. What was the divergence time estimated by Meyers et al (2012) for AMH and denisovans?  41. What is F4 statistics? What is the difference between this method and Patterson’s D statistic?  

42. Draw the main types of complex demographic model. Who tested it? How it was tested and which model  is more likely to be true?  

43. Define introgression.  

44. What are the ways of testing gene flow?  

45. What is ABBA-BABA test? Who created it?  

46. Given the following sequences, draw what would be more likely to be the tree, ABBA-BABA pattern.  Does this tree suggest migration/ gene flow?

Lineage 1

A

G

C

G

A

T

G

G

A

Lineage 2

A

T

T

G

C

G

C

T

T

Lineage 3

A

T

C

T

A

G

C

T

T

Lineage 4

A

G

T

T

C

T

G

A

C

47. What means Patterson’s D test is D=0? And when it is different from zero?  

48. Define Rind and Rpop. Given the following genome from 10 individuals from each population, give Rind  and Rpop and what their numbers represents. What each line represents?

Europeans East Asians

49. The following table show alleles from different individuals which has 5 SNPS that were characterized as  being Neanderthal-derived alleles. By using Patterson’s D method, give the answers.  Location of SNP 1 2 3 4 5 

African C A C T T 

European T C C A G

Asian T A T A T 

Neanderthal T C T A G

Chimpanzee C A C T T 

a. Is there possible to say that it has an excess of Neanderthal derived alleles in AMH from Europe when  comparing with Africa?  

b. In the same way, is there an excess of Neanderthal derived alleles in AMH from African when  comparing with Europe?  

c. How much Neanderthal derived alleles African and European share?  

50. What was new about Prufer et al (2014)?

51. Which demographic models Prufer et al (2014) tested? Which model were more likely to be true?  52. Why mitochondrial DNA analysis got a different structural NJ tree than when analyzing nuclear genome?

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