Population and Evolutionary GeneticsThe Nature and Origin of Biological DiversitySubject of evolutionary biology is nature and origin of biological diversity:• diversity of individuals within species• diversity of species in the biosphereBiological diversity matters! Population and evolutionary genetic data andtheory are used intensively in conservation, agriculture, medicine, physicalanthropology, and genomics.Population and evolutionary genetics studies diversity at the level of genes:• measure amount and kind and look for patterns. (How many genes or bp aredifferent in two humans? Are some genes more variable than others?)• explain it in terms of mutation, random drift, natural selection, sexualreproduction, migration, etc. (Why are the genes for fibrinopeptides morevariable than the genes for cytochrome c? Why do introns evolve faster thanexons?)Population and evolutionary genetics reconstructs the history of life. (Arehumans more closely related to chimpanzees or gorillas? Did Homo sapiens andH. neanderthalensis interbreed? When did the multicellular animals arise?)Population Genetics is the study of• genetic diversity among individuals, within species (or populations)• mechanisms that determine the amount of diversity• short-term evolutionary changes in organisms (short-term = thousands ortens of thousands of generations)Evolutionary genetics is the study of the• genetic differences between species• long-term evolution of genes and genomesRoughly speaking• population genetics compares different copies of a gene within a species• evolutionary genetics compares a gene in two different speciesBoth are governed by the same basic forces, of which the most important are:• mutation universal• random genetic drift universal• natural selection universal• sexual reproduction in sexual species• migration in subdivided populationsAlthough some processes are universial, they are not equally important!AS ?S/AAS/AAS/AASS/AAHomo sapiens?Charles Darwin and Alfred Russell Wallace• Knew about evolution (as did many others at that time).• Knew that all organisms share a common ancestor and that life can beportrayed as a tree.• Knew that there is great variation among species, but didn’t know thatvariation originates by mutation.• Knew that variation is inherited, but didn’t know about genes, had poortheory of inheritance.• Knew that natural selection acts on variation to cause adaptation inorganisms, but didn’t know about some other forms of selection, and didn’tknow about random drift.Darwin would be happily amazed to see what we have learned aboutevolutionary genetics. For example, my colleague Michael Nachman and hisstudents, especially Hopi Hoekstra (now at Harvard University), showed thatpocket mice living on lava flows are very dark while those living on sandy areasare light, and that this adaptive difference is due to one or a few mutations in aspecific pigmentation gene.Start with an example.Marty Kreitman cloned and sequenced ll different copies of the Adh geneencoding alcohol dehydrogenase from different strains of Drosophila melanogaster.Nowadays the genes are amplified by PCR and the sample sizes are much larger,e.g. 100 flies. The sequences must be aligned before comparison, but this is easilydone because the differences between them are small, and the alignments areunambiguous.Computers will translate the DNA sequences into protein sequences. Below is analignment of exon 4 from three of Kreitman's sequences and from two differentspecies, D. willistoni and D. virilis.• The D. simulans sequence is identical to one of the D. melanogaster sequences. D.simulans is a close relative of D. melanogaster, based on similarity of other genes andof morphology. Phylogeny:Note evolutionary lineages leading to melanogaster and virilis split before the onesleading to melanogaster and simulans. Differences reflect mutations that accumulatedalong the branches. Differences proportional to branch lengths:melanogaster -simulans = a + b = 2 a melanogaster-virilis = a + c + d = 2 (a + c)Variation within a species:• Drosophila melanogaster is polymorphic = has ≥ 2 alleles of Adh. The sequencesfall into two classes, those with threonine (T) and those with lysine (K) at site#25. This difference was previously detected by using starch gelelectrophoresis. All D. melanogaster populations are polymorphic, with bothFast and Slow alleles.SFAdhF/AdhF AdhF/AdhS• In the entire coding sequence (exons 1 + 2 + 3 + 4), there is only site where differentcopies of the Adh gene from D. melanogaster differ in amino acid sequences.Now look at the DNA sequence:The bp difference at site 74, Cvs. A, is the one that causes thedifference between threonineand lysine at amino acid 25.This is a change in the secondcodon position.There are a number of otherdifferences between the threeAdh genes from D.melanogaster, and also betweenthe three species. Most of theseare synonymous differences =differences that change fromone codon to a synonymouscodon and hence don’t change anamino acid. E.g. site 15: codondifference ATC vs. ATT, bothcode for isoleucine. Change inthird codon position, where mostchanges are synonymous/silent.Patterns in molecular genetic variation to explain:• DNA sequences > amino acid sequences.• synonymous > nonsynonymousAdh gene has introns and flanking sequences as well as exons.• flanking ≈ introns > exonsConserved sequences = (nearly) invariante.g.ATG start codonPromoterAll mutations very detrimental or lethal.• Functionally important regions tend to be conserved.So can look for conserved regions and they are likely to be important.This illustrates recurring theme:3 kinds of mutations with respect to natural selection:• Neutral: no effect on fitness (number of offspring produced by individualwith mutation)• Detrimental (= deleterious): decrease fitness, usually eliminated by naturalselection• Advantageous: increase fitness, favored by natural selection, rareNeutral variation is most common type, because most non-neutral mutationsare detrimental and individuals carrying them reproduce less.Mutations are more often detrimental in genes or regions that are less variable(more conserved).We will spend the remainder of my lectures talking about biological diversitywithin species and about differences between species: how biological diversity ismeasured; and the mechanisms that govern it: mutation,