Keith Browning
Dr. Ely
BIOL770
Term Paper
The Landscape and Origin of Ancient DNA in Anatomically Modern Humans
Since the successful genome sequencing of the ancient hominids Neanderthal and Denisovan, there has been the question of what proportion of the anatomically modern humangenome is also present in the genome of ancient hominids (Sankararaman et al. 2014). The next issue is the question of how this genetic material came to be part of modern human DNA. Was it through introgression/hybridization at some point after Homo sapiensformed as a distinct species? Or do modern humans share polymorphisms with Neanderthal and Denisovans simply due to the sharing of a common ancestor?Also what is the distribution across modern human populations of Neanderthal/Denisovan-like DNA?
Potential ancient DNA sequences are typically less than 100 kilobases in length.(Sankararaman et al. 2014) Using the 1000 genomes projectSankararaman et al. found Neanderthal haplotypesin the genomes of 1004 contemporary humans. Using the genomes of six other primates, to determine which alleles are pre-Neanderthal ancestral, along with Neanderthal and modern human DNA, it was found that the probability of particular alleles to be passed down from Neanderthals was much higher in European and East-Asian individuals than in African individuals (Sankararaman et al. 2014). The Neanderthal contribution to modern genomes was estimated to be 1.38% for east Asians, 1.15% for European and 0.08% for African populations (Sankararaman et al. 2014).Neanderthal-like DNA is present in ~64% of European genomes and 62% of East Asian genomes(Sankararaman et al. 2014). An example of the probability of particular genes being of Neanderthal in origin is shown in the figure below (Sankararaman et al. 2014).
Using genetic sampling as well as the 1000 Genome Project, a particular Denisovan haplotype (37 kilobase pair in length) was found to be the primary haplotype found in Tibetans and a secondary Haplotype in Han Chinese populations (Herta-Sanchez et al. 2014).
The distribution of Neanderthal and Denisovan-like DNA appears to be segregated to European and Asian populations. It is the popular thought that a proto-human species left Africa and from that point evolved into Neanderthals, Denosovans, and other related hominids. While still in Africa the species Homo sapienarose then migrated into Europe and Asia. At this point in the history of Homo sapiens, it is possible that introgression occurred through hybridization with Neanderthals and Denosovans outside of Africa. This is evidenced by the landscape of ancient DNA in anglo-europeans and Asian populations (Sankararaman et al. 2014). But there is still the question of the amount of archaic admixture found in African populationsthat are descendent from Homo sapienswho did not migrate from Africa to eventually encounter and hybridize with Neanderthal or Denosovan populations.How genetically isolated was the population that gave rise to anatomically modern Humans? Fossil evidence shows that Africa provided a greater opportunity for introgression than Europe and Asiasince there were a large number of ancient forms of humans coexisting with anatomically modern humans in Africa (Hammer et al. 2011).
Using samples gathered from 3 sub-Saharan populations (San, Biaka Pygmies and Mandenka) of modern humans, computer modelling wasperformed using 61 non-coding autosomal regions of DNAlooking for patterns of linkage disequilibrium. Linkage disequilibriumis the non-random association of alleles at multiple sites on the genome(Reich et al. 2001). These modeling approaches were intended to predict the sequence of nucleotides expected in sample DNA without (null-hypothesis)and with (alternative hypothesis) gene flow from an ancient hominid species(Hammer et al. 2011). Two approaches were used, a two population model and a three population model, testing the null hypothesis as well as estimating three specific parameters. These parameters were: the ancestral split time(To), the time of admixure(Ta) and the admixture porportion(a).
The results of these models reject the null hypothesis that there was no admixture in African Homo sapiens, the likelihood has a conservative P value of 0.0493(Hammer et al. 2011). Instead, the models suggest that modern African populations contain a small portion of genetic material, approximately 2% of their genome, this is introgressed from an ancient, now-extinct, species of hominid(Hammer et al. 2011). This hominid is distinct from the ancestor species of Homo sapiens, having split off from that lineage around 700 kya. The introgression event is modelled to have occurred around 35 kya. A potential candidate as an introgression site is a ~31.4 kilobase region within the 4qMB179 locus. The haplotypes found at this location are highly divergent(Hammer et al. 2011).
There is still the concern that perhaps these shared genetic sequences are a result common ancestral polymorphisms and not past introgression into Homo sapiens. Using a statistics tool to determine the relatedness of two populations relative to a third ancestor control (chimpanzees) Lowery et al. conducted a study contrasting whether modern human traits are derived traits or ancestor traits of Neanderthals. Lowery et al. noticed that there was absolutely no overlap between European and Neanderthal DNA in mitochondria or on the Y chromosomes, which clashes with the apparent presence of Neanderthal DNA in 64% of Europeans (Lowery et al. 2014).After reviewing the data, it is the opinion of Lowery et al. that these genetic affinities are likely a result of the retention of ancient mutations across time.
However, a possible example of introgressed DNA is found in the genomes of 41 Tibetans. The Tibetan genome is found to be highly divergent from the most closely related humans (Han Chinese) in a particular in a 32.7 kilobase region (Herta-Sanchez et al. 2014).This divergence is highlighted in the figure below.
Within this region a 5 SNP base motif (AGGAA) was found contained in a 2.5 kilobase windowin Tibetans (Herta-Sanchez et al. 2014). This 5 SNP haplotype is found to match up exactly with the Denisovan haplotype at the same AGGAA site. Furthermore, across the entire 32.7 kilobase site,the Tibetan’s common haplotype shares with the Denisovan 15 out of 20 identical SNPswith the Denisovan haplotype (Herta-Sanchez et al. 2014). These similarities in SNPs are not shared to this extent with any other extant sampled populations. The number of difference found between the Tibetan common haplotype and the Denisovan haplotype was found to be consistent with the number expected after an introgression event (Herta-Sanchez et al. 2014). It was found that the chance of having this 32.7 kilobase fragment maintained down two different lineages from a common ancestor species was highly unlikely (P=.0012). Also the theory of having these two very similar haplotypes as a result of a shared ancestor doesn’t account for this haplotype being almost entirely absent in all other populations(Herta-Sanchez et al. 2014).
There also is strong evidence supporting the hypothesis of introgression being the force responsible for the genetic similarities between modern humans and Neanderthal/Denisovans. The alternate hypothesis of these similaritiesbeing the result of polymorphisms passed down from a common ancestor has less support, but does raise some interesting points. It will be interesting to see if more large pieces of introgressed DNA like the 32.7 kilobase region in Tibetans can be found in the large European and Asian populations that have Neanderthal/Denisovan-like DNA. Discoveries like this will go a long way towards building a more accurate understanding of Ancient DNA in modern humans.
Literature Cited
Hammer MF, Woerner AE, Mendez FL, Watkins JC, Wall JD (2011) genetic evidence for archaic admixture in Africa. PNAS 37:15123-15128 doi: 10.1073/pnas.1109300108
Huerta-Sanchez E, Jin X, Asan B, Zhuoma P, Benjamin M, Vinckenbosch N (2014) Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA.Nature 7513:194-197 doi:10.1038/nature13408
Lowery R, Uribe G, Jimenez E, Weiss M, Herrera K, Regueiro M, Herrera R (2013) Neanderthal and denisova genetic affinities with contemporary humans: Introgression versus common ancestral polymorphisms. Gene530:83-94doi: 10.1016/j.gene.2013.06.005
Reich D, Cargill M, Bolk S, Ireland J, Sabeti P, Richter D, Lander E (2001)linkage disequilibrium in the human genome. Nature 411:199-204 doi:10.1038/35075590
Sankararaman S, Mallick S, Dannemann M, Prüfer K, Kelso J, Pääbo S, Reich D (2014) the genomic landscape of neanderthal ancestry in present-day humans. Nature,507:354-357 doi:10.1038/nature12961.