Human origins and evolutionGil McVean, Department of Statistics, OxfordQuestions about human origins• What defines a human?• What does the fossil record tell us?• What are the genetic changes that make us human?• What are the genetic changes that make people(s) different?

What makes us human?• Upright posture, bipedalism• Advanced tool-making capability• Big brain, relative to body size, and small canine teeth• Global dispersal• Use of fire to modify environment• Language and ‘consciousness’ (self-awareness)• Complex culture

Human brain size• Humans have an encephalisation quotient of about 6.5 – 8.0– The biggest of any mammal!Mammals:

Ebrain = 0.12 x Mbody2/3

What is culture?• Language• Beliefs• Rituals• Law• Morality• Manners• Visual arts

Great ape phylogeny• Human and chimp ancestors split about 6 MYA

Hacia JG (2001)

A recent X?• Suggestion of a more recent divergence time for X chromosome– Patterson et al (2006) Some terminology• Hominid is a term used to describe Humans and any lineages that share a common ancestor with humans more recently than the human-chimp split

An overview of the fossils

Human – chimp splitOrigin of H. sapiens sapiens

Australopithecus• 3.9 – 3 MYA• Both gracile and robust forms (latter called Paranthropus)• Evidence for sexual dimorphism within these speciesAustralopithecus boisei

Australopithecus robustus

Australopithecus afarensis (Lucy)

Australopithecus africanus

The Laetoli footprints• First evidence of bipedalism• 3.7 MYA• Three sets of tracks in volcanic ash

Lucy• 3.2 MYA from Ethiopia• Lucy was bipedal, an adaptation for travel across savannah woodlands and grasslands• Big teeth, still not a big brain.Early Homo species

Homo habilis• 2.6 – 1.4 MYA• Some, but not all, have slightly bigger brains• Maker of tools (Oldowan tools)Striding out, standing tall, and at last, a big brain

• Turkana boy (1.5 million years ago): the earliest individual with estimated brain size (909cc) significantly above primate allometrycurve.• Homo ergaster

Brain size versus height

H. ergaster lived in Eurasia at same time as in Africa• Dmanisi fossils date to 1.7 mya• Caucasus Mountains, Republic of Georgia (well north of the tropics)• Associated Oldowan tools• H. ergaster is the first species of hominin adapted for endurance running.

Why leave Africa? The role of Pleistocene climate change

Onset of Lower Pleistocene glaciations at ~2 million years ago with formation of permanent ice sheets and sharp cooling. Africa becomes drier.

Warm

• Middle Pleistocene climate: colder and more variable; long cold glacial periods punctuated by short, warmer interglacials• Migrations of many species between Africa and Eurasia during interglacials

What is life in the Pleistocene like for early Homo species?• Hunting game as well as scavenging • Control of fire– Possibly from 2MYA• Improving the tool kit – more elaborate Acheulean stone tools: e.g. handaxe for butchering• Increasingly complex social behaviour

Homo erectus did cross sea barriers• Archaeology on Flores, dates to 840,000 years ago• H. florensiensis(Hobbits) on Flores date to as recently as 20,000 yrs agoHobbit on left compared with modern human

Homo sapiens neanderthalensis• From H. heidelbergensis (0.75 – 0.25 MYA)• Only found in Europe and near East• Diverged from AMH lineage about 0.8 MYA• More robust than AMH, but shared many features of culture– Music – Jewellery– Complex tools– Ritual (burial of dead)– Language ability?

Homo sapiens sapiens• Anatomically modern humans (AMH)• Modern anatomy at 200,000 years ago (Ethiopia – Omo I and II)• Out-of-Africa event 70,000 years ago

Out of Africa: diversity among early modern Homo sapiens(a) Skhul 5, Israel,

90,000 Yrs

(b) Cro-Magnon 1, France, 23-27 KYrs

(c) Kow Swamp, robust Aboriginal Australian, 9-13 KYrs

Shared features: Cranial vault height high and domed, brow ridges lighter or absent, chin present

Dispersal of AMHs out of Africa• Into Middle East by 90,000 years ago, and then retreat. (Neanderthal distribution expands)• Reach Australia by 60,000 years ago, apparently via south Asian coastal route.• 40,000 years ago: substantial presence of moderns in Europe and Asia (little evidence in archaeological record at earlier dates)• Last Neanderthals about 25,000 years ago• Bottleneck in dispersal out of Africa - implicated by genetic data– Note that this bottleneck is not associated with speciation, only with modest structure between sub-Saharan and other human populations.

What does genetic variation tell us about human evolution?• Modern humans appear in the fossil record about 200K years ago• The mitochondrial Eve dates back to about 150K years ago• The Y-chromosome Adam dates back to about 70K years ago• AMHs left Africa about 70KYA• For most of our genome, however, the common ancestor is about 500K – 1M years ago– This predates the origin of Homo sapiens considerably

Did early humans interbreed with Neanderthals?

Ovchinnikov et al (2000)

Neanderthals

mtDNA sequences say no…

But…• There is some evidence for this in the presence of unusual haplotypes found in Europe composed of SNPs not found in non-European populations

Plagnol and Wall (2006)

Deeper trees in the human genome• There is growing evidence that some regions of our genome have truly ancient common ancestors• Dystrophin has an ancient haplotype found primarily outside Africa suggesting a colonisation of >160KYA• There is an inversion found primarily in Europeans that is roughly 3MY oldStefansson et al (2005)

Haplotype 1

Haplotype 2

What are the genetic differences that make us human?

Chromosomal changes• Human chromosome 2 is a fusion of two chromosomes in great apes• There are several inversion differences between the chromosomesFeuk et al (2005)

Gene loss• Loss of enzymes that make sialicacid – Sugar on cell surface that mediates a variety of recognition events involving pathogenic microbes and toxins • Myosin heavy chain– Associated with gracilizationWang et al (2006)

Gene evolution• FOXP2 is a highly conserved gene (across the mammalia), expressed in the brain. Mutations in the gene in humans are associated with specific language impairment• Across the entire mammalian phylogeny, there have only been a very few amino acid changing substitutions• However, two amino acid changes have become fixed in the lineage leading to modern humans since the split with the chimpanzee lineageEnard et al. (2002)

What are the genetic differences that make people and peoples

different?

How do we differ? – Let me count the ways• Single nucleotide polymorphisms– 1 every few hundred bp• Short indels (=insertion/deletion)– 1 every few kb• Microsatellite (STR) repeat number– 1 every few kb• Minisatellites– 1 every few kb• Repeated genes– rRNA, histones• Large inversions, deletions– Y chromosome, Copy Number Variants (CNVs)

TGCATTGCGTAGGCTGCATTCCGTAGGC

TGCATT---TAGGCTGCATTCCGTAGGC

TGCTCATCATCATCAGCTGCTCATCA------GC≤100bp

1-5kb

Detecting recent adaptive evolution• Let’s look closely at the dynamics of the fixation process for adaptive mutations• The fixation of a beneficial mutation is associated with a change in the patterns of linked neutral genetic variation• This is known as the hitch-hiking effect (Maynard Smith and Haigh 1974)• Looking for the signature of hitch-hiking can be a good way of detecting very recent fixation events

Diversity is not evenly distributed across genes II• Adaptive evolution ‘wipes out’ diversity nearby due to the hitch-hiking effects of a selective sweep– e.g. Duffy-null locus in sub-Saharn africa, protects against P. vivaxPop1

Pop2

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European

African

FY*O mutation

Ancestral alleleDerived alleleMissing dataHamblin and Di Rienzo (2000)

Long haplotypes• A selective sweep at the Lactase gene in Europeans Strong population differentiation

Lamason et al (Science 2005)

• SLC24A5

Classes of selected genes

Voight et al. (2005)