Tuesday, March 11, 2014

Origins of Australian aborigines and a unified hybridization model of human evolution: integrating informative data from autosomes, Y chr, and mtDNA

I am going to Spain in a few days for the Cell Symposium on Human Evolution on March 16-18th to present a poster as shown below (my lab website has a better resolution file for download, http://www.sklmg.edu.cn/articles_98.shtml?l=en-us. The introduction and main conclusions, as copied from the poster, is in the following.
A common difficulty for all existing models of human evolution has been to account for  the unusual diversity and admixed features of the Australian aborigines (AUA). A list of morphological features aimed at defining modern humans would exclude both modern AUA and Neanderthals, indicating some shared traits between the two. Fossil studies lack fine resolution power and molecular studies have yet to produce even just an internally coherent model uniting autosomes, Y chr, and mtDNA, let alone consistency with fossils/phenotypes and common sense. Almost every ancient DNA finding has been a surprise to the existing models, the latest being the 400K year old Heidelbergensis.
Molecular studies have so far relied on the Neutral theory and its infinite sites assumption. The Neutral theory was originally inspired by the so called molecular clock which was in turn inspired by the first and most remarkable result in molecular evolution, the genetic equidistance result that sister species are approximately equidistant to a simpler outgroup. In recent papers, we have shown that the equidistance result has been incorrectly interpreted by the molecular clock with grave consequences on phylogenetic studies: nearly all past studies have used non-informative DNAs assumed to be neutral but have now been shown by us to be under selection. We have developed the maximum genetic diversity (MGD) hypothesis to absorb and supersede the neutral theory. From this more correct/complete theoretical perspective that has coherently accounted for all major known observations, we developed new methods and studied the origins of humans using the 1000 genomes project and other public data. 
We found direct evidence of higher MGD or lower purifying selection for African San and Pygmy specific Y chr that will dramatically rewrite Y phylogeny. Certain regions of Y with low contents of repetitive DNAs have few SNPs in all Y haplotypes except being highly variable in A and B. But in other regions, similar degrees of variations are found for all haplotypes. Thus, the apparent deep separation or distance between A and B or between A/B and other haplotypes is not related to time as is commonly assumed. San/Pygmies have more positions in their genomes that when mutated are not deleterious to their physiology, which creates higher MGD and in turn higher innate or natural adaptive capacity required for a primitive life style.
Two types of DNAs are a priori informative to phylogenetic studies: slow evolving neutral DNAs from autosomes are informative to separation time and functional DNAs from mitochondria (mt) and Y chr are informative to shared internal physiology. Non-informative to phylogeny but informative to adaptation to outside environments are the fast evolving DNAs (speed is essential for quick adaptation to fast changing environments). We verified the informative nature of different SNPs by testing whether autosomes can reveal the known admixture history of Mexicans (MXL): those with R1b3 Y haplotype should have relatively more European and less Chinese autosomes than those with Q haplotype; those with B2 mtDNA should be the closest to the autosomes of B2 Northern Chinese. The slow evolving SNPs gave the expected result while all other autosome SNPs produced only senseless results.
Integrating autosomes, Y and mtDNA, we found just two original branches of humans, Europeans with R1a Y chr and U2 mtDNA and Africans with B and L1c, with a conservatively estimated split time of 2.1 million years. All other Y or mt branches originated by admixture and adaptive co-evolution as evidenced by autosomes data. We found a farmers-associated SNP3010 with highest frequency in D4 Chinese and what may be gene conversions in mtDNA in admixed humans (data not shown due to space limitations). Southern Chinese (CHS) O2 Y-chr and B2 mtDNA were the oldest or least admixed Asian group and derived from admixture of R1a/U2 Europeans and B/L1c Africans before leaving Africa for Asia. Heidelbergensis, Denisovans, and Neanderthals were descendants of a more recent interbreeding event in Iberia between migrating Africans and local Europeans, who then moved across Eurasia and became direct ancestors of AUA. These results suggest a unified hybridization model consistent with physical/cultural traits and fossil records, which explains the wide diversity of Australian aborigines. Since the original branching of two groups, further diversification of humans occurred largely by repeated cycles of migration/hybridization followed by independent evolution followed by further migration/hybridization, an intuitively expected pattern if homo has been a single species since the first co-appearance of H. habilis and H. rudolfensis.