Genomic architecture and functional effects of potential human inversion supergenes.

Supergenes are involved in adaptation in multiple organisms, but they are little known in humans. Genomic inversions are the most common mechanism of supergene generation and maintenance. Here, we review the information about two large inversions that are the best examples of potential human supergenes. In addition, we do an integrative analysis of the newest data to understand better their functional effects and underlying genetic changes. We have found that the highly divergent haplotypes of the 17q21.31 inversion of approximately 1.5 Mb have multiple phenotypic associations, with consistent effects in brain-related traits, red and white blood cells, lung function, male and female characteristics and disease risk. By combining gene expression and nucleotide variation data, we also analysed the molecular differences between haplotypes, including gene duplications, amino acid substitutions and regulatory changes, and identify CRHR1, KANLS1 and MAPT as good candidates to be responsible for these phenotypes. The situation is more complex for the 8p23.1 inversion, where there is no clear genetic differentiation. However, the inversion is associated with several related phenotypes and gene expression differences that could be linked to haplotypes specific of one orientation. Our work, therefore, contributes to the characterization of both exceptional variants and illustrates the important role of inversions. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.

The Early Peopling of the Philippines based on mtDNA.

Despite the efforts made to reconstruct the history of modern humans, there are still poorly explored regions that are key for understanding the phylogeography of our species. One of them is the Philippines, which is crucial to unravel the colonization of Southeast Asia and Oceania but where little is known about when and how the first humans arrived. In order to shed light into this settlement, we collected samples from 157 individuals of the Philippines with the four grandparents belonging to the same region and mitochondrial variants older than 20,000 years. Next, we analyzed the hypervariable I mtDNA region by approximate Bayesian computation based on extensive spatially explicit computer simulations to select among several migration routes towards the Philippines and to estimate population genetic parameters of this colonization. We found that the colonization of the Philippines occurred more than 60,000 years ago, with long-distance dispersal and from both north and south migration routes. Our results also suggest an environmental scenario especially optimal for humans, with large carrying capacity and population growth, in comparison to other regions of Asia. In all, our study suggests a rapid expansion of modern humans towards the Philippines that could be associated with the establisment of maritime technologies and favorable environmental conditions.

Genome-wide data from the Bubi of Bioko Island clarifies the Atlantic fringe of the Bantu dispersal.

BACKGROUND: Bioko is one of the few islands that exist around Africa, the most genetically diverse continent on the planet. The native Bantu-speaking inhabitants of Bioko, the Bubi, are believed to have colonized the island about 2000 years ago. Here, we sequenced the genome of thirteen Bubi individuals at high coverage and analysed their sequences in comparison to mainland populations from the Gulf of Guinea. RESULTS: We found that, genetically, the closest mainland population to the Bubi are Bantu-speaking groups from Angola instead the geographically closer groups from Cameroon. The Bubi possess a lower proportion of rainforest hunter-gatherer (RHG) ancestry than most other Bantu-speaking groups. However, their RHG component most likely came from the same source and could have reached them by gene flow from the mainland after island settlement. By studying identity by descent (IBD) genomic blocks and runs of homozygosity (ROHs), we found evidence for a significant level of genetic isolation among the Bubi, isolation that can be attributed to the island effect. Additionally, as this population is known to have one of the highest malaria incidence rates in the world we analysed their genome for malaria-resistant alleles. However, we were unable to detect any specific selective sweeps related to this disease. CONCLUSIONS: By describing their dispersal to the Atlantic islands, the genomic characterization of the Bubi contributes to the understanding of the margins of the massive Bantu migration that shaped all Sub-Saharan African populations.