January 18th, 2012 class

With Kimura-sensei.

Human evolution

“genjin” left Africa 20-10 man years ago.
Then “kyujin” (Neanderthal), and “shinjin” (us) – Neandethals expanded range a bit, but we expanded a lot. We were able to adapt to many environments, changing genotypes and phenotypes, lifestyles too.

Menu
1. Evolution
2. Pop gen
3. Genome analyses – tough, but can learn about genome analyses, don’t have to learn all!

1. Evolution
Darwin and Lamarck intro. Could be good to distinguish between the two.
Important points: a. DNA to RNA to proteins. DNA info.
b. cellular structure
c. gametes.
Discusses allele selection and natural mutations. Most mutations disappear, but a few stay. Stay by either selection or random!

Neutral evolution: random mutation, not directly apparent on selection.
Natural selection: of course, as explained.

1.5-3 mya, very diverse time. P. bosei, P. robustus, P. ethiopicus, A. africanus, H. habilus, H. ludorufeo. H. ergaster.

Order: Use of tools, then into Europe, then into Asia, then use of fire.

Maybe different theories on human evolution. Diverse ancestors, or all one group, or reticulate evolution, or half and half. Humans are one group, with some small reticulate evolution.

H. erectus was alive until recently, and also Neanderthal was in Europe same time as H. sapiens. "Heidelberg man" alive until recent in Mongolia/Tibet.

2. Pop gen.

Humans have 23 chromosomes. Ome=all (zentai). Genome, proteome, etc. 22 normal and 1 X/Y!

Chromosome structure. Chromatid, telomere, centromere, etc. Also introduce DNA base pairs, AGCT. A and G purines, C and T pyrimidines. A and T bond, etc.

Types of DNA mutation.
1. Translocation – multimegabase to chromosome, or monosomy, trisomy. Change in ploidy.
2. Kilobase to megabase: Tandem duplication, deletion, inversion
3. 10s to few kilobases: Alu element insertion, minisatellite, element insertion.
4. Few base pairs: substitution, single indels, microsats. E.g. SNPs. Transitions more common than transversions (C to T, G to A).

Discusses DNA and inheritance from each parent, plus mutations. Polymorphism, and how some stay in populations, and some disappear. How this can also lead to new species. Can compare number of changes with molecular clock.

Y and mtDNA do not recombine.

Genetic drift and founder effect. Uses example of alleles in population (gene pool) and how it can happen.

Small sizes can have harsh genetic drift much more easily. N=20 always rapidly fixes, n=1000 not much but changes. Bottleneck and founder event.

For humans, mtDNA has lots of mutations. Y chromosome too.

Y follows paternal, mtDNA follows maternal. Therefore can follow wide range of evolution. Be careful making assumptions using only one side of DNA, missing lots of the story!! By doing the genome, we can look at the rest of your ancestors. mtDNA’s Eve is the same thing – be careful! Y Adam is the same.
MRCA=most recent common ancestor.

Thus, much DNA has incomplete lineage sorting. Adding more DNA markers and you can get complete lineage sorting.

Genome:
2003 Human genome project finished.
Then, SNP project. HapMap.
Human Genome Gene Chip – 5man to 100 man SNPs (in one day). Next generation sequencer – soon a genome for 1000 USD.
Can envision reading all babies when born (!).

Genome-wide association study (GWAS); demography (pop movement etc/pop structure), natural selection, ancestral spp analyses.
a. GWAS: e.g. finding SNPs that link with human height. Weedon et al. 2008 etc. and related studies, now over 100 SNPs linked with height. Best to get all 100 SNP information, then calculate height.
b. Genome wide SNP, compare internal pop structure with distance from other populations. Infer pop history. E.g. Novembre et al. 2008 – mapping data fits with geographical history. Also migration in Polynesia; Tonga is mix of E Asia and PNG (Kimura et al. 2008; Price et al. 2008). Also examine admixed populations, understand how many generations have passed since admixing occurred.
c. Asia Pacific people came from E Asia. Several times of admixing/splitting.

Whole genome analyses:
Can use whole genome (n=2) of 1 person, can infer population size. With multiple people’s genomes, can infer sizes of populations in past. All infer serious bottleneck of 5000 people or so 50000 ybp. Do bottlenecks fit natural patterns? Usually to infer pop size, many samples, but can actually do this with whole genome! (Li et al. 2011).
Gronau et al. 201? – Bayesian inference from 6 genomes. All say humans evolved 50000 years ago. African populations split a long time ago.

Positive selection looks to fix must faster than neutral evolution (via selective sweep).

Population specific positive selection (selective sweep). Can look at human genotypes and phenotypes to examine this. Examples: Alcohol dehydrogenase, EDAR, etc.

Neanderthal genome – 1 to 4% in our genome!