1 Ancient DNA: would the real Neandertal please stand up? Eur. - - PDF document

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Ancient DNA: would the real Neandertal please stand up?

Multiregional continuity model:

• Transition between archaic and modern forms took place within a single evolutionary lineage.
• The single lineage is composed of geographic sub-populations connected by gene flow.
• Gene flow prevents independent evolution in the sub-populations
• The lineage originated in Africa about 2 million years ago in Homo erectus
• H. erectus left Africa and disperses into other parts of the world
• Regional variation reflects natural selection for local adaptations
• H. sapiens emerged from a lineage-wide process of evolution
• Archaic forms of Homo are subspecies (e.g., H. sapiens neanderthalensis)

Replacement model:

• H. sapiens evolved as a new species in a sub-population (probably Africa)
• The H. sapiens lineage originated about 150-200, thousand years ago
• H. sapiens lefts Africa and dispersed to other parts of the world.
• H. sapiens displaces the pre-existing hominids; no interbreeding occurs
• Under this model the preexisting populations of Homo in Europe and elsewhere are species

(e.g., H. erectus; H. ergaster; H. heidelbergensis; H. neanderthalensis)

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Ancient DNA: would the real Neandertal please stand up?

• H. sapiens

(modern)

• H. sapiens

(archaic)

• H. erectus
• H. habilis

1,800,000 ybp 500,000 ybp 100,000 ybp

Afr. Asia Eur. Afr. Asia Eur.

Modern human “Out of Africa” dispersal

Multiregional continuity model Replacement model

Ancient DNA: would the real Neandertal please stand up?

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Gibraltar 2 Neandertal child

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Ancient DNA: would the real Neandertal please stand up? Loads of data are relevant to the controversy:

• Anatomical structures
• Archeological evidence
• Genetics (Modern Humans and Neandertals; we will focus on these…)

Anatomical structures indicate substantial differences:

Neandertal morphology:

• evolved over a period of 220,000 years (350k to130k ybp).
• final morphological form reached at 130,000 ybp.
• Neandertals are first hominids to adapt to cold mid-latitude climates.

“Human” morphology:

• appear in fossil record about 140,000 ybp (robust)
• Appear elsewhere around 60,000 ybp
• Modern humans arrive in Europe 40,000 ybp and begin to displace (?) Neandertals

1. Some argue that coexistence of morphologically distinct forms, and subsequent displacement, supports the “replacement” model. 2. Others point out that coexistence in Europe could have lasted as long as 10,000 years and that some early modern humans exhibit a mosaic of archaic and modern features. [But, discrete Neandertals and modern humans coexisted in Middle East for about 55,000 years] [A morphologically intermediate skeleton was found in Portugal, having a Neandertal-like skeleton and more modern skull. The conclusions that this might be a hybrid is

• controversial. The date of the skeleton (24,500) is very late, and there are issues about

what a hybrid anatomy should look like]

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Archeological evidence :

Neandertals and modern humans:

• very similar up to 40-50,000 ybp
• After 40-50,000 ybp anatomically modern humans undergo a “creative explosion”
• The “creative explosion” appears to have begun in Africa and spread outward.

1. Supporters of the replacement model argue that this period of innovation has a genetic basis and represents gene flow as well as cultural flow

• 2. Supporters of the continuity model argue that transmission could have been purely by

social mechanisms and point out that there are no changes in skull morphology during the period of the outward spreading of the “creative explosion” Sites in southern France reveal populations of Neandertals using (mimicking) the culture

• f modern humans associated with the creative explosion. No clearly intermediate

morphologies at this site.

Extant human mtDNA polymorphism supports “Out of Africa”

Africans dominate the root of the human mtDNA tree Consistent with the “Out of Africa model”; i.e, that Africa was the source for contemporary human mtDNA diversity

African populations have the most polymorphism. Some argue that they must be oldest, because they have accumulated the most mutations.

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Krings et al. (1997) conclude:

• Neandertals went extinct without

contributing mtDNA to modern humans

• Used as outgroup, the Neandertal

sequence supports the “Out of Africa” hypothesis of modern humans

• Modern human and Neandertal mtDNA

coalesce at 500,000 ybp Ancient DNA:

• single neandertal
• 30,000 years old (max 100,000)
• HVI of mt control region: 387 bp
• Great effort to authenticate the ancient

DNA (aDNA)

There are now 8 Neandertal aDNA sequences

The shaded area indicates the known range of Neanderthals. Mezmaiskaya is the location where the baby Neanderthal whose DNA was sequenced was found. An earlier Neanderthal DNA sequence was determined from bones found in Feldhofer Cave in Germany.

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Ancient DNA: would the real Neandertal please stand up?

Neanderthal Homo sapiens sapiens Homo sapiens idaltu 160,000 years old, Clearly suggest African origin

The oldest modern human DNA is not from Africa

Neandertal Oldest Modern Human DNA [LM3: > 55,000 ybp]

LM3 is the oldest reliably dated modern human. LM3 lived >55,000 ybp LM3 was Australian The LM3 mtDNA lineage diverged before the MRCA of living humans, but has gone extinct Contemporary diversity at a single locus cannot be used to infer the pattern of human evolution

Remember that Homo sapiens idaltu is from Africa Given an African origin for H. sapiens, these genetic results clearly indicate an im portant role for genetic drift in explaining the m odern patterns of genetic diversity of hum ans

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All the phylogenetic analyses that include Neandertal DNA indicate a substantial divergence of the mtDNA lineages BUT, what about genetic drift? Random sampling from one generation to the next means that some lineages will become extinct by chance alone; i.e., stochastic lineage sorting will occur

Australian LM3

This Human and Neanderthal pair are each others closes genetic relatives [ in this sample of lineages]

Homo sapiens idaltu Homo sapiens sapiens Homo neandertalensis mtDNA represents just a single genetic locus!

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So, divergence of lineages is not evidence on its own. Coalescent models can be used to answer the question: “How much introgression could have occurred without leaving any evidence of Neandertal mtDNA in the modern human population?”

Species 1 Species 2 Species 3 Species 4

• you want to look at such patterns over many loci!

Published in PLOS (2005)

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Assumptions:

• Complete displacement along a

narrow front of a spatially expanding human population.

• Population growth is logistic. This

means that introgressed neandertal genes are not lost by drift; rather they are amplified.

If we assume a different model, as much as 25% introgression could occur and we would not see any Neandertal mtDNA lineages within the human population

Some alternative views:

Reanalysis of Neandertal data Published in 2002 Results sensitive to substitution model Divergence of Neandertal lineage is not supported under more sophisticated substitution models

Best-fit model Best-fit model Suboptimal model

A robust modern human mandible Discovered in 2002 (pub. 2003) Dated to 34-36,000 ybp “presents a mosaic of archaic, early modern human, and possible Neandertal morphological features”

What should a hybrid look line, anyway?

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The controversies continue. The replacement model seems to have greater support. Would the real Neandertal please stand up?

That was the story in 2005

Possible survival

• f archaic alleles

more closely related to Neanderthals Potential introgression of Neanderthal alleles

Minimum contribution of archaic gene pool to modern humans: 5%

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Nature VOL 444 16 November 2006

In 2006 began the discipline of Neanderthal genomics…

Hum an-chim p: ~ 98% identical (~ 35 million nucleotide differences) Hum an-Neanderthal: ~ 99.5% identical (~ 1.5 million differences)

62,250 base pairs Estimated coalescent times 1 million base pairs Estimate effective population sizes

The earliest point at which genealogies diverged that ultimately gave rise to the hum and Neanderthal reference sequences Estimated time of split of ancestral populations

(95% CI on contribution of Neanderthal to human genome: 0 – 20%)

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Nature VOL 444 16 November 2006

Modern Humans Ne: ~ 10,000 Archaic Humans Ne: ~ 20-40,000 Chimp (gorilla, orang) Ne: ~ 20-40,000 Human-Neanderthal CA Ne: ~ 3,000 (0-12,000)

Neanderthal X chromosome shows higher divergence than autosomes: gene flow from human males to Neanderthals (mtDNA datasets do not record male Neanderthal contributions to modern humans)

Expect to see a complete Neanderthal genome sequence sometime in the next few years; it holds the promise of answering many controversial questions about human evolution

In 2006 began the discipline of Neanderthal genomics…

That was the story in 2006

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The retrieval of Neanderthal (Homo neanderthalsensis) mitochondrial DNA is thought to be among the most significant ancient DNA contributions to date, allowing conflicting hypotheses

• n modern human (Homo sapiens) evolution to be tested directly. Recently, however, both the

authenticity of the Neanderthal sequences and their phylogenetic position outside contemporary human diversity have been questioned. Using Bayesian inference and the largest dataset to date, we find strong support for a monophyletic Neanderthal clade outside the diversity of contemporary humans, in agreement with the expectations of the Out-of-Africa replacement model of modern human origin. From average pairwise sequence differences, we obtain support for claims that the first published Neanderthal sequence may include errors due to postmortem damage in the template molecules for PCR. In contrast, we find that recent results implying that the Neanderthal sequences are products of PCR artifacts are not well supported, suffering from inadequate experimental design and a presumably high percentage (>68%) of chimeric sequences due to "jumping PCR" events.

Note: 95% Bayesian credibility interval includes non-monophyltic clades

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Neanderthals appeared to have survived well after the arrival of modern humans in Europe (up to 28-24 kya)

Issues surrounding ancientDNA resurface: stability, contamination, etc. Perhaps archeology and anatomy will lead to more satisfactory answers?

In 2007 we found more questions than answers