Xu Shuhua's team analyzed the adaptive evolution of vitamin B1 metabolism genes in East Asian populations

November 15, 2022, iScience The research results of Xu Shuhua's team from the School of Life Sciences of Fudan University "Archaic introgression contributed to the pre-agriculture adaptation of vitamin B1 metabolism in East Asia"
were published online.
The study analyzed 3823 whole genomes of the global population, combined with ancient DNA data, and found vitamin B1 The genes involved in metabolic pathways are subject to specific positive natural selection in East Asian populations; This study further identifies the origin of adaptive haplotypes in East Asian populations, and estimates the timing and potential evolutionary drivers
of specific natural selection in East Asian populations.
The results suggest that there may be differences in the metabolic capacity and mechanism of vitamin B1 in East Asian populations and other populations in the world, which provides clues and scientific basis
for population genetics and evolutionary biology for further research and application of precision medicine and precision nutrition.

Vitamin B1 is an essential micronutrient that plays important functions
in carbohydrate metabolism and the immune system.
Beriberi due to vitamin B1 deficiency was widespread
in East Asia in the 19th and 20th centuries where rice was the staple food.
In the search for ways to prevent beriberi, vitamin B1 was discovered, and then multivitamins
, which are now widely known.
Today, large-scale vitamin B1 deficiencies are rare
.
However, several new forms of vitamin B1 deficiency
remain.
For example, studies have found that diabetic patients generally have symptoms
of low plasma vitamin B1 content.
In addition, studies have found that vitamin B1 supplementation can improve immune system function
.
Studies have shown that vitamin B1 supplementation can be used as an adjunct to the treatment of new crown patients
.
These findings have led to an increasing focus
on vitamin B1.
However, most of the relevant research has focused on vitamin B1 supplementation to eliminate the corresponding vitamin B1 deficiency symptoms, and the lack of vitamin B1 Genetic study
of genes involved in metabolic pathways.
Is there a difference in the metabolic capacity of vitamin B1 between people? What is the genetic basis for this difference? Questions like these remain unclear
.

The study was first based on the analysis of whole genome sequencing data from 3823 global populations and found 7 involvement in the vitamin B1 metabolic pathway There are 3 genes encoding proteins (SLC19A2, SLC35F3,).
SLC35F43) differed significantly between East Asian populations and populations on other continents (Figure 1); For example, some gene haplotypes reach very high frequencies in East Asian populations, but are completely missing in African populations, and are missing or have very low frequency in European populations, suggesting that haplotypes of these genes are specific in East Asian populations, and further analysis shows that these genes have undergone positive natural selection
in the evolutionary history of East Asian populations.

1: Vitamin B1 metabolism genes are specifically and naturally selected
in East Asian populations.

The study further traced the origin of adaptive haplotypes and found that the adaptive haplotypes of SLC35F3 and SLC35F4 may have originated in ancient humans
.
By analyzing the genome sequences of these genes such as adaptive haplotypes and Neanderthals, it was found that the adaptive haplotypes of SLC35F4 and Neanderthal haplotypes had a very high matching rate (>90%).
It is highly likely that this haplotype originated from the genetic exchange between modern human ancestors and Neanderthals or similar ancient humans
.
Interestingly, the adaptive haplotype of SLC35F3 does not match the thousands of samples that have been measured so far on the ancient genomes of modern human ancestors (usually dated within 10,000 years, mostly for).
1000-4000 year range), which also indicates that adaptive evolution occurred 10,000 years ago
.
However, whether it originated from ancient people who have not yet sampled still needs to be further explored
.

An important function of vitamin B1 is to promote the metabolism
of carbohydrates.
To examine whether changes in population dietary structure after the onset of agriculture in East Asia are the evolutionary driver of this adaptive selection
.
By analyzing the genomic data of contemporary populations and combining the genomic data of paleomodern humans in different historical periods, the study estimates the frequency of
selected haplotypes in different historical periods.
It was found that the selected haplotype had reached high frequencies one year ago, while the frequency had not changed significantly in the past one year (Figure 2).

The results of this analysis further show that adaptive evolution was completed
1 year ago.
This may also suggest that changes in the diet of people after the onset of agriculture are not the original driver of natural selection
.

2.
Adaptive selection occurred in East Asia 10,000 years ago
.

Overall, the study found genes associated with the vitamin B1 metabolic pathway (SLC19A2, SLC35F3,).
SLC35F4 East Asian populations are subject to specific positive natural selection, some of which are adaptive haplotypes derived from genetic exchanges in extinct Neanderthals or similar ancient humans, and it is inferred that the adaptive evolution specific to East Asian populations is likely to occur before agricultural civilization in East Asia, suggesting that changes in the dietary structure of East Asian populations after large-scale agricultural development are not the primary evolutionary driving force
of adaptive evolution.

The study's findings suggest that there may be differences
in the ability to metabolize vitamin B1 in East Asian populations and populations on other continents.
Further functional experiments and large population cohort studies can help uncover whether vitamin B1 requirements differ
between individuals of different genetic backgrounds.
From the perspective of evolution, studying the differences of nutrient metabolism genes among populations and exploring their formation mechanisms is helpful to understand the genetic basis and molecular mechanism of differences in the metabolic ability of people with different genetic backgrounds on nutritional elements, and ultimately promote the development of quasi-medicine and the formulation of population-specific nutritional standards
.

Ma Xixian, a postdoctoral fellow at the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, is the first author of the paper; Professor Xu Shuhua from the School of Life Sciences, Fudan University is the corresponding author
of the paper.
This work has been supported by the Shanghai "Super Postdoc" incentive program, and supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences Pilot Project, and the Shanghai International Human Phenotyping Group Program Municipal Science and Technology Major Special Project
.

Link to paper: 01886-7