Genetic Chaos

Tuesday, November 28, 2006

Modern Humans Did Not Admix with Neanderthals during Their Range Expansion into Europe

The process by which the Neanderthals were replaced by modern humans between 42,000 and 30,000 before present is still intriguing. Although no Neanderthal mitochondrial DNA (mtDNA) lineage is found to date among several thousands of Europeans and in seven early modern Europeans, interbreeding rates as high as 25% could not be excluded between the two subspecies. In this study, we introduce a realistic model of the range expansion of early modern humans into Europe, and of their competition and potential admixture with local Neanderthals. Under this scenario, which explicitly models the dynamics of Neanderthals’ replacement, we estimate that maximum interbreeding rates between the two populations should have been smaller than 0.1%. We indeed show that the absence of Neanderthal mtDNA sequences in Europe is compatible with at most 120 admixture events between the two populations despite a likely cohabitation time of more than 12,000 y. This extremely low number strongly suggests an almost complete sterility between Neanderthal females and modern human males, implying that the two populations were probably distinct biological species.

PDF file

Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage

At the center of the debate on the emergence of modern humans and their spread throughout the globe is the question of whether archaic Homo lineages contributed to the modern human gene pool, and more importantly, whether such contributions impacted the evolutionary adaptation of our species. A major obstacle to answering this question is that low levels of admixture with archaic lineages are not expected to leave extensive traces in the modern human gene pool because of genetic drift. Loci that have undergone strong positive selection, however, offer a unique opportunity to identify low-level admixture with archaic lineages, provided that the introgressed archaic allele has risen to high frequency under positive selection. The gene microcephalin (MCPH1) regulates brain size during development and has experienced positive selection in the lineage leading to Homo sapiens. Within modern humans, a group of closely related haplotypes at this locus, known as haplogroup D, rose from a single copy ~37,000 years ago and swept to exceptionally high frequency (~70% worldwide today) because of positive selection. Here, we examine the origin of haplogroup D. By using the interhaplogroup divergence test, we show that haplogroup D likely originated from a lineage separated from modern humans ~1.1 million years ago and introgressed into humans by ~37,000 years ago. This finding supports the possibility of admixture between modern humans and archaic Homo populations (Neanderthals being one possibility). Furthermore, it buttresses the important notion that, through such adminture, our species has benefited evolutionarily by gaining new advantageous alleles. The interhaplogroup divergence test developed here may be broadly applicable to the detection of introgression at other loci in the human genome or in genomes of other species.

PDF file

Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens

The tau (MAPT) locus exists as two distinct clades, H1 and H2. The H1 clade has a normal linkage disequilibrium structure and is the only haplotype found in all populations except those derived from Caucasians. The H2 haplotype is the minor haplotype in Caucasian populations and is not found in other populations. It shows no recombination over a region of 2 Mb with the more common H1 haplotype. The distribution of the haplotype and analysis of the slippage of dinucleotide repeat markers within the haplotype suggest that it entered Homo sapiens populations between approx. 10000 and 30000 years ago. However, sequence comparison of the H2 haplotype with the H1 haplotype and with the chimp sequence suggests that the common founder of the H1 and H2 haplotypes was far earlier than this. We suggest that the H2 haplotype is derived from Homo neanderthalensis and entered H. sapiens populations during the coexistence of these species in Europe from approx. 45000 to 18000 years ago and that the H2 haplotype has been under selection pressure since that time, possibly because of the role of this H1 haplotype in neurodegenerative disease.

PDF file

Friday, November 03, 2006

Geographical, Linguistic, and Cultural Influences on Genetic Diversity: Y-Chromosomal Distribution in Northern European Populations

We analyzed 10 Y-chromosomal binary markers in 363 males from 8 populations in Northern Europe and 5 Y microsatellites in 346 of these individuals. These populations can be grouped according to cultural, linguistic, or geographical criteria, and the groupings are different in each case. We can therefore ask which criterion best corresponds to the distribution of genetic variation. In an AMOVA analysis using the binary markers, 13% of the Y variation was found between populations, indicating a high level of differentiation within this small area. No significant difference was seen between the traditionally nomadic Saami and the neighboring, historically farming, populations. When the populations were divided into Uralic speakers and Indo-European speakers, 8% of the variation was found between groups, but when they were divided according to geographical location, 14% of the variation was between groups. Geographical factors have thus been the most important in limiting gene flow between these populations, but linguistic differences have also been important in the east.

PDF file

Y-chromosome diversity in Sweden – A long-time perspective

Sixteen Y-chromosomal binary markers and nine Y-chromosome short tandem repeats were analyzed in a total of 383 unrelated males from seven different Swedish regions, one Finnish region and a Swedish Saami population in order to address questions about the origin and genetic structure of the present day population in Sweden. Haplogroup I1a* was found to be the most common haplogroup in Sweden and accounted, together with haplogroups R1b3, R1a1 and N3, for over 80% of the male lineages. Within Sweden, a minor stratification was found in which the northern region Va¨sterbotten differed significantly (Po0.05) from the other Swedish regions. A flow of N3 chromosomes into Vasterbotten mainly from Saami and Finnish populations could be one explanation for this stratification. However, the demographic history of Vasterbotten involving a significant male absence during the 17th Century may also have had a large impact. Immigration of young men from elsewhere to Varmland at the same time, can be responsible for a similar deviation with I1a* haplotypes. Y chromosomes within haplogroup R1b3 were found to have the highest STR variation among all haplogroups and could thus be considered to be one of the earliest major male lineages present in Sweden. Regional haplotype variation, within R1b3, also showed a difference between two regions in the south of Sweden. This can also be traced from historical time and is visible in archaeological material. Overall this Y chromosome study provides interesting information about the genetic patterns and demographic events in the Swedish population.

PDF file

Y-Chromosomal Variation in the Czech Republic

To analyze the contribution of the Czech population to the Y-chromosome diversity landscape of Europe and to reconstruct past demographic events, we typed 257 males from five locations for 21 UEPs. Moreover, 141 carriers of the three most common haplogroups were typed for 10 microsatellites and coalescent analyses applied. Sixteen Hg's characterized by derived alleles were identified, the most common being R1a-SRY10831 and P-DYS257*(xR1a). The pool of haplogroups within I-M170 represented the third most common clade. Overall, the degree of population structure was low. The ages for Hg I-M170, P-DYS257*(xR1a), and R1a-SRY10831 ap peared to be comparable and compatible with their presence during or soon after the LGM. A signal of population growth beginning in the first millennium B.C. was detected. Its similarity among the three most common Hg's indicated that growth was characteristic for a gene pool that already contained all of them. The Czech population appears to be influenced, to a very moderate extent, by genetic inputs from outside Europe in the post-Neolithic and historical times. Population growth postdated the archaeologically documented introduction of Neolithic technology and the estimated central value coincides with a period of repeated changes driven by the development of metal technologies and the associated social and trade organization.

PDF file

Significant genetic differentiation between Poland and Germany follows present-day political borders, as revealed by Y-chromosome analysis

To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n = 913) and 11 from Germany (n = 1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r = 0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmonier's algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies.

PDF file