EGI Notes

Friday, June 3, 2016

Human Biology News, 6/3/16

Rapid human evolution and Northeastern European autoimmunity.

Read here, excerpts, emphasis added:

Two studies presented at the Biology of Genomes meeting here last week show how our genomes have changed over centuries or decades, charting how since Roman times the British have evolved to be taller and fairer, and how just in the last generation the effect of a gene that favors cigarette smoking has dwindled in some groups
…With the help of giant genomic data sets, scientists can now track these evolutionary shifts in allele frequencies over short timescales….Pritchard's team analyzed 3000 genomes collected as part of the UK10K sequencing project in the United Kingdom. For each allele of interest in each genome, Field calculated a “singleton density score” based on the density of nearby single, unique mutations. The more intense the selection on an allele, the faster it spreads, and the less time there is for singletons to accumulate near it. The approach can reveal selection over the past 100 generations, or about 2000 years.
Stanford graduate students Natalie Telis and Evan Boyle and postdoc Ziyue Gao found relatively few singletons near alleles that confer lactose tolerance—a trait that enables adults to digest milk—and that code for particular immune system receptors. Among the British, these alleles have evidently been highly selected and have spread rapidly. The team also found fewer singletons near alleles for blond hair and blue eyes, indicating that these traits, too, have rapidly spread over the past 2000 years, Field reported in his talk and on 7 May in the preprint server bioRxiv.org. One evolutionary driver may have been Britain's gloomy skies: Genes for fair hair also cause lighter skin color, which allows the body to make more vitamin D in conditions of scarce sunlight. Or sexual selection could have been at work, driven by a preference for blond mates…
…In a sign of the method's power, Pritchard's team also detected selection in traits controlled not by a single gene, but by tiny changes in hundreds of genes. Among them are height, head circumference in infants, and hip size in females—crucial for giving birth to those infants. By looking at the density of singletons flanking more than 4 million DNA differences, Pritchard's team discovered that selection for all three traits occurred across the genome in recent millennia.
Joseph Pickrell, an evolutionary geneticist at the New York Genome Center in New York City, has used a different strategy to put selection under an even keener microscope, detecting signs of evolution on the scale of a human lifetime. He and Przeworski took a close look at the genomes of 60,000 people of European ancestry who had been genotyped by Kaiser Permanente in Northern California, and 150,000 people from a massive U.K. sequencing effort called the UK Biobank…
..In the parents' generation, for example, the researchers saw a correlation between early death in men and the presence in their children (and therefore presumably in the parents) of a nicotine receptor allele that makes it harder to quit smoking. Many of the men who died young had reached adulthood in the United Kingdom in the 1950s, a time when many British men had a pack-a-day habit. In contrast, the allele's frequency in women and in people from Northern California did not vary with age, presumably because fewer in these groups smoked heavily and the allele did not affect their survival. As smoking habits have changed, the pressure to weed out the allele has ceased, and its frequency is unchanged in younger men, Pickrell explains. “My guess is we are going to discover a lot of these gene-by-environment effects,” Przeworski says.
Indeed, Pickrell's team detected other shifts. A set of gene variants associated with late-onset menstruation was more common in longer-lived women, suggesting it might help delay death. Pickrell also reported that the frequency of the ApoE4 allele, which is associated with Alzheimer's disease, drops in older people because carriers died early. “We can detect selection on the shortest timeframe possible, an individual's life span,” he says


Differences in gut microbes, particularly early in life, are likely to contribute to a person's susceptibility to autoimmunity. Vatanen et al. explored this phenomenon by comparing the microbiomes of children from Finland, Estonia, and Russia from birth to 3 years old. Russians have lower incidences of autoimmunity than Finns and Estonians, and their microbiomes early in life differed, too, with Finnish and Estonian children harboring larger amounts of Bacteroides species. The primary source of bacterial lipopolysaccharide (LPS), an immunomodulatory molecule, also differed among the children. Bacteroides-derived LPS, which probably dominates in Finnish and Estonian children, did a poor job of teaching immune cells self-tolerance in cell culture and in mice, suggesting that it may contribute to autoimmune susceptibility in these populations.
Cell 165, 842 (2016).

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