Presentation on theme: "Population Migration and the Variation of Dopamine D4 Receptor (DRD4) Allele Frequencies Around the Globe Moira Maxwell."— Presentation transcript:
1Population Migration and the Variation of Dopamine D4 Receptor (DRD4) Allele Frequencies Around the GlobeMoira Maxwell
2DopamineThe neurotransmitter dopamine plays a huge role in the body, and has been implicated in ADHDD4 is a dopamine receptor gene that has 2-11 repeat units.DRD4 in humans is linked to:Novelty-seekingHyperactivityRisk-taking behaviorsThese are typical ADHD behaviorsConsistent with findings in animal studies:Increase in exploratory behaviorIncrease in speed and locomotionThese behaviors are adaptive for maximizing resources in a new environment
4HypothesesPopulations with a history of migration in the past 1, ,000 years will show high rates of DRD4 alleles.Macro-migration: Populations that have migrated many thousands of miles will show a higher rate of DRD4 alleles than populations who have not migrated as far.Micro-migration: Populations that use sedentary subsistence strategies will have a lower percentage of DRD4 alleles than nomadic populations.
5Methods12 studies with a total sample size of 2,320 individuals with no psychiatric disorders from 39 countries were analyzed.4,640 alleles looking for the proportion of 7-repeats the proportion of long alleles as an index of genotype in a population
6Macro-migrationEstimated in thousands of miles (kmiles) of population from homeland of its language family.Based on the archeological record and historical linguisticsMacro-migrations occured 1,000-30,000 years ago
76 Main Migration RoutesAmerican Indians- NE Asia>North America>Central and South AmericaChina>Japan/Taiwan/SE Asia/The PacificJews>Ethiopia/Yemen/EuropeWest Africa>Central/Eastern/Southern AfricaBlack Sea>Europe(Indio Europeans)Melanesians>SE Asia
9Macro-migration hypothesis A strong correlation of r =.85 (p<.001) was found between kmi traveled and DRD4 long allele frequency distributionsSupports hypothesis for macro-migrationused a solid p-value
10Fig 1C. Chen et al.of correlations. A more accurate view is that autocorrelation increases the variance
11Micro-MigrationMeasures survival strategies used by the 39 societies in this analysis.Societies were coded as either sedentary=0 (28 societies) or as nomadic=1 (11 societies)Nomadic populations had a 10.4% higher rate of DRD4 long alleles than sedentary ones.
12Micro-migration hypothesis A correlation of r =.52 (p<.001) was found between percentage of long alleles and subsistence type in a populationSupports hypothesis for micro-migration
13Macro and micro-migration Correlation of macro and micro-migration was r =.39 (p<.05)Regression analysis showed that macro-migration was a better indicator of DRD4 allele frequency than micro-migrationFor every kmi away from homeland, the proportion of DRD4 long alleles increased by 4.3%
14The confound of Auto-correlation Occurs when sampling units are not independentLeads to Type I error (rejecting null when it is actually true)All societies in this study have had contact with other societies, making it hard to discern if there is an effect of auto-correlation or not. This is particularly true of American Indians who are known to share common ancestry with each other.Researchers corrected for this by including all available data in order to increase sample sizeAfter correction, hypothesis for macro-migration was still supported, but not as strongly for micro-migration as p-value dropped from p<.001 to p<.11
15Does the bottleneck effect explain the results? Populations that are isolated after migration experience a bottleneck effect because of a limited gene pool.None of the other 128 alleles examined followed the migratory patterns of the populations
16DRD4 allele frequency and migration Correlation found? YesCausation? Three competing hypotheses“Founder’s effects” or“Natural selection/deselection”Spontaneous mutation - can rule this out because r is too high to be by chance
17Founder’s effects hypothesis Populations migrated because of the genetic makeup of their membersMore long alleles in population would increase exploratory behavior which may increase group migrationDRD4 allele frequencies seen in early populations would be the same in modern populations
18Natural selection / deselection Forced migration due toWarDepletion of natural resources causing famineNatural selection in populations that adapted to multiple migrations would cause an increase of DRD4 genesIn sedentary populations, lack of migration would cause a deselection of DRD4 long alleles.
19How to testIdeal solution: Compare genetic data from populations that is at least 15,000 years old (pre-agriculture) and compare that with modern genetic data on frequency of DRD4 alleles.This is not possible yet, so the authors chose the proximate mechanism of testing DRD4 frequency in modern day immigrants and in their counterparts remaining in country of origin.
21ResultsTable 3 shows a lack of support for the “Founder’s effects” hypothesis as DRD4 frequency rates are the same for immigrants and non-immigrantsFounder’s hypothesis and NS/dS hypothesis are competing, so therefore the “Natural selection/deselection” hypothesis is supported.
22Natural selection/deselection Humans began as nomadic foragers who migrated away from their places of origin repeatedly. Researchers believe there would have been strong pressure to select for genes that favored exploratory behaviors. Repeated migrations would continue to increase the frequency of these genes.~15,000 years ago humans began to use agriculture rather than hunter-gathering. Populations who did not migrate far after agriculture would have deselected for migratory genes.Deselection appears to explain the effects micro-migration on DRD4 frequencies.
23ADHDThought to be a result of selective pressures on migratory behaviors.Very adaptive then, but not in our (almost) exclusively sedentary modern societies.Evolutionary time-lag: If society persists as sedentary for long enough, a decrease in ADHD will be seen as it will no longer be adaptive.
24Further testing Testing on non-human primates Are there high rates of DRD4 long alleles in other populations with macro-migration?
25Global rates of ADHDWorldwide rate of ADHD is 5.2% (Polanczyk et. al, 2007)“The North American rate (6.2%) only slightly exceeded the European rate (4.6%). The highest rates emerged from Africa (8.5%) and South America (11.8%). Corroboration comes from a dimensional ADHD scale used in 21 countries. Japanese and Finnish children scored lowest, Jamaican and Thai children scored highest, and American children scored about average.” (Moffitt and Melchior, 2007)