Search for: All records

The persistence of versions of genes that cause severe disease in human populations has long perplexed scientists. It is common for many versions of a gene to exist. But scientists expect that over time natural selection will eliminate versions of genes harmful to human health. Sometimes, there are good reasons that a disease-causing gene may persist. For example, having two copies of a particular gene variant causes a condition, called sickle cell disease. But having one sickle cell-causing copy of the gene and one non-disease-causing copy protects against malaria. As a result, the version of the gene that causes sickle cell is more common in people from areas where malaria is prevalent despite the risks to people who end up with two copies. Scientists call this phenomenon balancing selection because trade-offs in the gene’s benefits and risks cause it to persist in the population. Aqil et al. show that balancing selection has likely caused many ancient gene variants to persist in human populations. In the experiments, Aqil et al. scoured the genomes of hundreds of modern humans from around the world and four groups of ancient human ancestors, including Neanderthals and Denisovans. The experiments looked for structural changes in genes, like deletions, that date back to more than 700,000 years ago – before modern humans split from their ancestors. They found large numbers of such ancient genes in modern humans. Using computer modeling, Aqil et al. showed that these ancient genes likely persist because of balancing selection. Many of these ancient genes regulate the immune response and metabolism. These genes may protect against infectious diseases outbreaks and starvation, which have occurred periodically throughout human history. But these same genes may cause immune or metabolic diseases in modern humans not currently facing these threats. The experiments show how such biological trade-offs have shaped human evolution and reveal that modern human populations, regardless of race or region of origin, share the same genetic variation that already our ancestors carried within them. 

The time, extent, and genomic effect of the introgressions from archaic humans into ancestors of extant human populations remain some of the most exciting venues of population genetics research in the past decade. Several studies have shown population-specific signatures of introgression events from Neanderthals, Denisovans, and potentially other unknown hominin populations in different human groups. Moreover, it was shown that these introgression events may have contributed to phenotypic variation in extant humans, with biomedical and evolutionary consequences. In this study, we present a comprehensive analysis of the unusually divergent haplotypes in the Eurasian genomes and show that they can be traced back to multiple introgression events. In parallel, we document hundreds of deletion polymorphisms shared with Neanderthals. A locus-specific analysis of one such shared deletion suggests the existence of a direct introgression event from the Altai Neanderthal lineage into the ancestors of extant East Asian populations. Overall, our study is in agreement with the emergent notion that various Neanderthal populations contributed to extant human genetic variation in a population-specific manner. 

Many mammals can digest starch by using an enzyme called amylase, but different species eat different amounts of starchy foods. Amylase is released by the pancreas, and in certain species such as humans, it is also created by the glands that produce saliva, allowing the enzyme to be present in the mouth. There, amylase can start to break down starch, releasing a sweet taste that helps the animal to detect starchy foods. Curiously, humans have multiple copies of the gene that codes for the enzyme, but the exact number varies between people. Previous research has found that populations with more copies also eat more starch; if this correlation also existed in other species, it could help to understand how diets influence and shape genetic information. In addition, it is unclear how amylase came to be present in saliva, as the ancestors of mammals only produced the protein in the pancreas. Pajic et al. analyzed the genomes of a range of mammals and found that the more starch a species had in its diet, the more amylase gene copies it harbored in its genome. In fact, unrelated mammals living in different habitats and eating different types of food have similar numbers of amylase gene copies if they have the same level of starch in their diet. In addition, Pajic et al. discovered that animals such as mice, rats, pigs and dogs, which have lived in close contact with people for thousands of years, quickly adapted to the large amount of starch present in human food. In each of these species, a mechanism called gene duplication independently created new copies of the amylase gene. This could represent the first step towards some of these copies becoming active in the glands that release saliva. In people, having fewer copies of the amylase gene could mean they have a higher risk for diabetes; this number is also tied to the composition of the collection of bacteria that live in the mouth and the gut. Understanding how the copy number of the amylase gene affects biology will help to grasp how it also affects health and wellbeing, in humans and in our four-legged companions.