Origins and Adaptation in Humans : A Case Study of Taste and Lifestyle

In this thesis, I use population genetics and statistical approaches to investigate early human demography, infer local adaptation in diverse sets of populations, and study the genetic basis for taste perception. In the first paper, I examine the genomic evidence for a severe bottleneck, which has been suggested based on paleontological and climate studies to coincide with the emergence of anatomically modern humans. Using a Bayesian approach, I evaluate the genetic evidence of a bottleneck between 190,000 and 130,000 years ago and find that the data is in favor of a model without bottleneck at this time point. I further develop a method to detect local adaptation based on frequencies of private haplotypes. I first show, using simulated data, that this method can detect local adaption. Applied to large-scale human genotype data, this method detects known signals of positive selection in human data such as the positive selection around the lactase gene in Europeans and East Africans. Also, this method permits to improve knowledge on potential adaptation events in humans as it finds several regions potentially selected that were not previously described. I further investigate patterns of adaptation in whole genome data based on a diverse set of African populations. The results from the regions potentially selected show that diet and pathogens are the common driving forces of adaptation in all studied populations. There is evidence that taste perception have evolved in concert with diet, environment, and the organismal needs in humans. For this reason, I study taste perception in populations differing on lifestyle (hunter-gatherers, farmers and nomad herders). I present taste perception phenotypes for all tastes (sweet, bitter, sour, salty and umami) and relate them to high density genotype data. I show that taste and taste-involved genes have evolved with lifestyle. By performing an association study, I also show that variation in taste perception involves more genes than only the taste receptors genes. In this thesis, by analyzing human genetic data with a population genetics approaches, I covered several topics of human ancient demography and adaptation and show the utility of using large-scale genetic data to better understand human history

Private haplotypes can reveal local adaptation

Background: Genome-wide scans for regions that demonstrate deviating patterns of genetic variation have become common approaches for finding genes targeted by selection. Several genomic patterns have been utilized for this purpose, including deviations in haplotype homozygosity, frequency spectra and genetic differentiation between populations. Results: We describe a novel approach based on the Maximum Frequency of Private Haplotypes - MFPH - to search for signals of recent population-specific selection. The MFPH statistic is straightforward to compute for phased SNP-and sequence-data. Using both simulated and empirical data, we show that MFPH can be a powerful statistic to detect recent population-specific selection, that it performs at the same level as other commonly used summary statistics (e.g. F-ST, iHS and XP-EHH), and that MFPH in some cases capture signals of selection that are missed by other statistics. For instance, in the Maasai, MFPH reveals a strong signal of selection in a region where other investigated statistics fail to pick up a clear signal that contains the genes DOCK3, MAPKAPK3 and CISH. This region has been suggested to affect height in many populations based on phenotype-genotype association studies. It has specifically been suggested to be targeted by selection in Pygmy groups, which are on the opposite end of the human height spectrum compared to the Maasai. Conclusions: From the analysis of both simulated and publicly available empirical data, we show that MFPH represents a summary statistic that can provide further insight concerning population-specific adaptation

Private haplotypes can reveal local adaptation

Background: Genome-wide scans for regions that demonstrate deviating patterns of genetic variation have become common approaches for finding genes targeted by selection. Several genomic patterns have been utilized for this purpose, including deviations in haplotype homozygosity, frequency spectra and genetic differentiation between populations. Results: We describe a novel approach based on the Maximum Frequency of Private Haplotypes - MFPH - to search for signals of recent population-specific selection. The MFPH statistic is straightforward to compute for phased SNP-and sequence-data. Using both simulated and empirical data, we show that MFPH can be a powerful statistic to detect recent population-specific selection, that it performs at the same level as other commonly used summary statistics (e.g. F-ST, iHS and XP-EHH), and that MFPH in some cases capture signals of selection that are missed by other statistics. For instance, in the Maasai, MFPH reveals a strong signal of selection in a region where other investigated statistics fail to pick up a clear signal that contains the genes DOCK3, MAPKAPK3 and CISH. This region has been suggested to affect height in many populations based on phenotype-genotype association studies. It has specifically been suggested to be targeted by selection in Pygmy groups, which are on the opposite end of the human height spectrum compared to the Maasai. Conclusions: From the analysis of both simulated and publicly available empirical data, we show that MFPH represents a summary statistic that can provide further insight concerning population-specific adaptation

Resequencing data provide no evidence for a human bottleneck in Africa during the penultimate glacial period.

International audienceBased on the accumulation of genetic, climatic, and fossil evidence, a central theory in paleoanthropology stipulates that a demographic bottleneck coincided with the origin of our species Homo Sapiens. This theory proposes that anatomically modern humans--which were only present in Africa at the time--experienced a drastic bottleneck during the penultimate glacial age (130-190 kya) when a cold and dry climate prevailed. Two scenarios have been proposed to describe the bottleneck, which involve either a fragmentation of the range occupied by humans or the survival of one small group of humans. Here, we analyze DNA sequence data from 61 nuclear loci sequenced in three African populations using Approximate Bayesian Computation and numerical simulations. In contrast to the bottleneck theory, we show that a simple model without any bottleneck during the penultimate ice age has the greatest statistical support compared with bottleneck models. Although the proposed bottleneck is ancient, occurring at least 130 kya, we can discard the possibility that it did not leave detectable footprints in the DNA sequence data except if the bottleneck involves a less than a 3-fold reduction in population size. Finally, we confirm that a simple model without a bottleneck is able to reproduce the main features of the observed patterns of genetic variation. We conclude that models of Pleistocene refugium for modern human origins now require substantial revision

Resequencing Data Provide No Evidence for a Human Bottleneck in Africa during the Penultimate Glacial Period

International audienceBased on the accumulation of genetic, climatic, and fossil evidence, a central theory in paleoanthropology stipulates that a demographic bottleneck coincided with the origin of our species Homo Sapiens. This theory proposes that anatomically modern humans--which were only present in Africa at the time--experienced a drastic bottleneck during the penultimate glacial age (130-190 kya) when a cold and dry climate prevailed. Two scenarios have been proposed to describe the bottleneck, which involve either a fragmentation of the range occupied by humans or the survival of one small group of humans. Here, we analyze DNA sequence data from 61 nuclear loci sequenced in three African populations using Approximate Bayesian Computation and numerical simulations. In contrast to the bottleneck theory, we show that a simple model without any bottleneck during the penultimate ice age has the greatest statistical support compared with bottleneck models. Although the proposed bottleneck is ancient, occurring at least 130 kya, we can discard the possibility that it did not leave detectable footprints in the DNA sequence data except if the bottleneck involves a less than a 3-fold reduction in population size. Finally, we confirm that a simple model without a bottleneck is able to reproduce the main features of the observed patterns of genetic variation. We conclude that models of Pleistocene refugium for modern human origins now require substantial revision