Adaptive evolution of vitamin B1 metabolism genes in East Asian populations

On November 15, 2022, iScience published the results of the Institute of Nutrition and Health, "Archaic introgression contributed to the pre-agriculture adaptation of vitamin B1 metabolism in East Asia"
。 The study analyzed 3823 whole genomes of the global population, combined with ancient DNA data, and found that the genes involved in the vitamin B1 metabolic pathway were 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 focuses on vitamin B1 supplementation to eliminate the corresponding symptoms of vitamin B1 deficiency, and there is a lack of genetic studies
of the genes involved in the vitamin B1 metabolic pathway.
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
.

Based on the analysis of whole genome sequencing data from 3823 global populations, the study found that 3 of the 7 protein-coding genes involved in the vitamin B1 metabolic pathway (SLC19A2, SLC35F3, SLC35F43) were significantly different in East Asian populations and other continental populations (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.

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

This study further traces the origin of adaptive haplotypes and finds that the adaptive haplotypes of SLC35F3 and SLC35F4 may have originated in ancient humans
.
By analyzing the genome sequences of adaptive haplotypes and Neanderthals and other ancient humans compared to these genes, it was found that the adaptive haplotypes of SLC35F4 and Neanderthal haplotypes had a very high matching rate (>90%), suggesting that this haplotype originated from the exchange of genes between modern human ancestors and Neanderthals or similar ancient people
。 Interestingly, the adaptive haplotype of SLC35F3 does not match the genome of ancient humans that have been measured so far, but whether it comes from ancient humans who have not yet been sampled still needs further exploration
.

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
.
The study analyzed genomic data from contemporary populations and combined with genomic data from different historical periods to estimate the frequency of
selective haplotypes in different historical periods.
It was found that the selected haplotypes had reached high frequencies 10,000 years ago, while the frequencies had not changed significantly in the last 10,000 years (Figure 2).

The results of this analysis further show that adaptive evolution was completed
10,000 years 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
.

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

Overall, the study found genes associated with vitamin B1 metabolic pathways (SLC19A2, SLC35F3, SLC35F4 East Asian populations are subject to specific positive natural selection, some of which are adaptive haplotypes derived from genetic exchanges between modern human ancestors and extinct Neanderthals or similar ancient humans, and it is inferred that the specific adaptive evolution of 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 the large-scale development of agriculture are not the primary evolutionary driving force
of adaptive evolution.

The results of the study 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 precision medicine and formulate 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 this paper; Professor Xu Shuhua from the School of Life Sciences of Fudan University is the corresponding author
of this 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 the paper: 01886-7