Julius B. Lucks/Meetings and Notes/SMBE2007/Plenary 1

= Marcus Feldman (Stanford): Continents, consumption and consumers - genetic signatures of human migration=

Words to Look Up

 * Microsatellite - a short tandem repeat that is repeated a variable number of times. The variation in the number of repeats can be used as an evolutionary marker.  High mutation rate due to slippage during replication.
 * homoplasy occurs when two 'things' have the same number of repeats (same character value), but got there by different paths
 * haplotype - the genetic composition of an individual chromosome
 * maximum-likelihood: with any system that has a conditional probabilty associated with a given state (ex: the probability of the observed population structure given a specified tree structure), the state with the highest conditional probability (i.e. - search over all trees to find the one that has the highest conditional probability).
 * see also parsimony: a way to construct trees that cause the smallest number of changes
 * example - suppose there are 4 leaves with nodes A,A,G,G, and say we are trying to distinguish between two trees, each with subtrees of 2 leaves. One tree has the structure ((A,A),(G,G)), the other ((A,G),(A,G)).  The former only requires one change to happen (grom the LCA), while the other requires 2, so the former would be selected by parsimony.
 * founder effect

Background
undergrad: mathematics, grad student stanford - straight to faculty

Talk

 * human population divisioned into different populations
 * Darwin, 'The Descent of Man', Blumenback - 5 divisions, Aggassiz - 8 divisions
 * Dobzhansky - '... populations of species that differ in the frequencies of one or more genetic varients, gene alleles, or chromosomal structures'

Patters from Y and mtDNA

 * 100 mt sequences, 600 sNips on human Y-Chromosomes
 * no recomb between these 2
 * see some continental differences - diff Y chromosome sNips

Autosomal Markers

 * Noah Resenburg, John Pritchard (software - STRUCTURE - Stanford/Chicago) - 783 microsattelites, 993 autosomal markers
 * STRUCTURE - clustering package
 * Conrad et. al., Nature Genetics, 2006
 * 'continental ancestry', not 'race' - reflect human migrations rather than something inherent
 * Kalash - ancestors of Alexander the Great's invasion of the Himalayas - somewhat of an outlier

Migration and its Complications

 * out of Africa II - exodus into the Levant to Europe/Asia, then Australia and the Americas
 * most likely did not have boats
 * way-point graph - Addis Ababa is the starting point
 * how genetic distance between pops related to their geographic distance?
 * r2 of 0.8 when correct for inability to travel large distances over water
 * serial founder effect - samples small group from pop - puts into empty nich and then grow
 * resample, put in new, grow
 * heterozygosity decreases with distance from Africa
 * lowest in the Americas
 * Himilayan barrier causes 2 clusters of population to appear
 * KB-Schroeder et. al. 2007, Biol. Lett, 3, 216

Some Analysis of the Americas

 * D9S1120 - microsattelite on chromosome 9
 * language tree fits fairly well with biological tree (783 markers)
 * mestizo population: higher European ancestry, greater heterozygosity
 * Africa > Europe > Asia > Americas - heterozygozity

Mycobacterium Tb: More Continental Structure

 * Peter Small - head of Gates Tb program - 800 mill year budget
 * collected every person for active Tb in San Francisco
 * ethnic origin, temporal
 * Tb insertion signal IR611 - marker

Questions

 * Do distinct varieties of Tb infect diff pops?
 * Are associations stable?
 * delete enough Tb, turns to Mycobateriem leprae

Tb

 * largely clonal
 * 1/3 world is infected
 * asymptomatic carrier state common
 * 1/10 carriers progress to active
 * transmission airborne, saliva

Conclusions

 * 3 phylogenetic geographic regions
 * host origin predicts strain variety
 * strong even when transmission in cosmopolitan urban center outside host origin
 * less transmission between major geographic regions than within
 * Gagneux, PNAS 2006
 * 2 hypotheses for distribution of TB into diff populations
 * TB travelled with humans 35,000 years ago
 * the existing diversity dispersed within the last 1,000 years ago (exploration)
 * possible that modern TB strains have been spreading across the world in the past 1000 years