Extended tracts of homozygosity around focal SNPs conferring lactose persistence

Association between three noncoding SNPs and lactose persistence in Africans LP, lactose persistent; LIP, lactose intermediate persistent; LNP, lactose non-persistent

Animal mitochondrial DNA- Functionally important yet rapidly evolving Glu NADH6 noncoding Pro Phe 12s rRNA Val Control Region 16s rRNA Thr Cyt b NADH1 Leu Ile Gln Met NADH5 NADH2 Leu Trp rRNA genes Ser Ala tRNA genes His Asn COI ATP synthase genes NADH4 Cys Asp Ser NADH4L NADH3 Cytochrome Oxidase COII Tyr Gly ATP6 Lys Arg ATP8 Cytochrome bc1 complex COIII NADH:Ubiquinone Oxidoreductase

Frequent deletions in human mitochondrial DNA

Mitochondrial disorders • Poor growth • Loss of muscle coordination, muscle weakness • Visual and/or hearing problems • Developmental delays, learning disabilities • Mental retardation • Heart, liver, or kidney disease • Gastrointestinal disorders, severe constipation • Respiratory disorders • Diabetes • Increased risk of infection • Neurological problems, seizures • Thyroid dysfunction • Dementia (mental disorder characterized by confusion, disorientation, and memory loss)

A mitochondrial mutation extending longevity

Higher frequency of homoplasmic C150T transitions in centenarians

Increase in nonsynonymous substitutions in terminal branches of human mtDNA

Amino acid constraint in 13 human mtDNA proteins

Climate adapted mtDNA mutations

Major histocompatibility complex Molecular evolution Conservation genetics Kin recognition Sexual selection/ parasites

The vertebrate major histocompatibility complex (Mhc) Class II Class III Class I LMP TAP DP DN DM DO DQ DR complement HSP70 B C X E J A H G F Human B A A B A A B B B A B A B B B A I II III I K TAP O complement D Q T M F M LMP A E Mouse HSP70 B A B B B B A B B A II II I II I II B-G TAP B-G rDNA Chicken A B B B B B II I HSP70 LMP complement Frog A B B B I

T-cells recognize peptides in the context of MHC molecules viral protein viral or bacterial pathogen cytotoxic T-cell peptide infected cell antigen presentation MHC TCR

Mhc class I crystal structure [ peptide binding region (PBR) peptide a1 domain a2 domain b2 microglobulin

Testing neutrality Under balancing selection, Tajima’s D > 0

Deep coalecsence of Mhc genes in humans

Ancient shared polymorphisms in primate MHC

Strong linkage disequilibrium in human MHC

32% of observed matings were with neighboring territorial ♂♂

Paternity analysis: 46% of progeny were sired by neighboring territorial ♂♂ with a strong preference for MHC dissimilar ♂♂

Odor Preference T-shirt study Women prefer odors of MHC-dissimilar males 2. “Smells like mate” 3. Contraception pill Wedekind et al. 1995

Observed copulations Number of ejaculations In-foster Cross-foster MHC-similar MHC-dissimilar Number of ejaculations In-foster Cross-foster

MHC Diversity Parasites Reproductive Mech. Mating, fertilization, abortion Parasites Red Queen (coevolution) Heterozygote advantage Parasite resistant offspring Inbreeding avoidance MHC Diversity