Human Y chromosome sequences from Q Haplogroup reveal a South American settlement pre-18,000 years ago and a profound genomic impact during the Younger Dryas.

The settlement of the Americas has been the focus of incessant debate for more than 100 years, and open questions regarding the timing and spatial patterns of colonization still remain today. Phylogenetic studies with complete human Y chromosome sequences are used as a highly informative tool to investigate the history of human populations in a given time frame. To study the phylogenetic relationships of Native American lineages and infer the settlement history of the Americas, we analyzed Y chromosome Q Haplogroup, which is a Pan-American haplogroup and represents practically all Native American lineages in Mesoamerica and South America. We built a phylogenetic tree for Q Haplogroup based on 102 whole Y chromosome sequences, of which 13 new Argentine sequences were provided by our group. Moreover, 1,072 new single nucleotide polymorphisms (SNPs) that contribute to its resolution and diversity were identified. Q-M848 is known to be the most frequent autochthonous sub-haplogroup of the Americas. The present is the first genomic study of Q Haplogroup in which current knowledge on Q-M848 sub-lineages is contrasted with the historical, archaeological and linguistic data available. The divergence times, spatial structure and the SNPs found here as novel for Q-Z780, a less frequent sub-haplogroup autochthonous of the Americas, provide genetic support for a South American settlement before 18,000 years ago. We analyzed how environmental events that occurred during the Younger Dryas period may have affected Native American lineages, and found that this event may have caused a substantial loss of lineages. This could explain the current low frequency of Q-Z780 (also perhaps of Q-F4674, a third possible sub-haplogroup autochthonous of the Americas). These environmental events could have acted as a driving force for expansion and diversification of the Q-M848 sub-lineages, which show a spatial structure that developed during the Younger Dryas period.

Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain.

Globally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades. Previous reports have demonstrated that Mp induced dysfunctional CD8+ cytotoxic T cell activity, suggesting that this strain has the ability to evade the immune response against M. tuberculosis. Comparative analysis of Mp and 410 genomes revealed non-synonymous polymorphisms in eleven genes and five intergenic regions with polymorphisms between both strains. Some of these genes and promoter regions are involved in the metabolism of cell wall components, others in drug resistance and a SNP in Rv1861, a gene encoding a putative transglycosylase that produces a truncated protein in Mp. The mutation in Rv3787c, a putative S-adenosyl-l-methionine-dependent methyltransferase, is conserved in all of the other prosperous M strains here analysed and absent in non-prosperous M strains. Remarkably, three polymorphic promoter regions displayed differential transcriptional activity between Mp and 410. We speculate that the observed mutations/polymorphisms are associated with the reported higher capacity of Mp for modulating the host's immune response.