The news column of Science magazine reported the research results of the hot spring snake series of the Li Jiatang research team of the Chinese Academy of Sciences

On October 11, the news column of Science magazine reported on the research results of the hot spring snake series of research results of Li Jiatang's research team at the Chengdu Institute of Biology of the Chinese Academy of Sciences under the title "Secrets of Tibet's hot-spring snakes revealed" (report link) (Figure 1).

Figure 1.
The News column of Science magazine reported the research results of Li Jiatang's research team on hot spring snakes

The article mentioned that since 2015, Li Jiatang's research team has focused on the research on the adaptation and evolution mechanism of extreme environments on the hot spring snake plateau, and published the draft genome of the Tibetan hot spring snake for the first time in 2018, and revealed the genetic mechanism of the hot spring snake species adapting to low oxygen and strong ultraviolet rays on the plateau, and the research results were published in PNAS
.
On this basis, the research team combined behavior, comparative genomics and patch-clamp experiments to further reveal the evolutionary genetic mechanism
of temperature sensing ability of hot spring snakes.
Based on the updated high-quality genomes, the team also carried out population genomics studies on Tibetan hot spring snakes and Sichuan hot spring snakes, providing important scientific support
for their conservation.
The research was published in The Innovation, Molecular Ecology and Zoological Research
.

The Qinghai-Tibet Plateau has the characteristics of cold climate, low oxygen content and strong ultraviolet rays, which is a great challenge for animals living on the plateau, and it is also a natural laboratory
for studying the adaptation of animals to high-altitude environments.
There have been previous studies on the genetic mechanism of humans and yaks in which thermostatic animals adapt to plateau environments, but there is a lack of relevant research on
ectothermic animals.
The hot spring snake is a good animal model
that solves the mystery of the high-altitude adaptation of ectothermic animals.

The genus Thermophis belongs to the snail-eating snake family and currently includes 3 species: the Tibetan hot spring snake Thermophis baileyi, and the Sichuan hot spring snake T.
zhaoermii and Shangri-La Spa Snake T.
Shangrila, they are a rare protected species endemic to China, a national first-class protected animal, and one of the snake groups with the highest distribution in the world, all living on the Qinghai-Tibet Plateau at an altitude of
3500–4400 meters.
The origin and evolution of the hot spring snake is closely related
to the formation and uplift of the Qinghai-Tibet Plateau.

Most snakes in the world live in tropical or subtropical regions, and the cold environment of the plateau is usually not conducive to snake
breeding.
As one of the highest distributed snake groups in the world, and being able to survive the dramatic climate changes of the plateau uplift and ice ages, the spa snake must have a special temperature adaptation strategy
.
Based on field investigation and literature research, the research team sorted out the distribution information of plateau geothermal resources and hot spring snakes, and found that hot spring snakes highly prefer hot spring
habitats.
Thermotaxis experiments have shown that hot spring snakes can locate high-temperature areas more quickly and show a strong preference for high-temperature areas compared with the other two low-altitude snakes, suggesting that hot spring snakes have efficient temperature sensing capabilities (Figure 2).

Figure 2.
Distribution of hot spring sites and hot spring snakes on the Qinghai-Tibet Plateau and behavioral experiments

Further comparative genomic analysis revealed that genes related to temperature sensing and regulatory ability in hot spring snakes underwent evolutionary changes, in which TRPA1 contained three amino acid substitutions unique to hot spring snakes, and mutations at these sites may change the spatial conformation of proteins and alter cation fluxing in transmembrane channels (Figure 3).

Patch-clamp experiments have shown that changes in these three sites do not lead to changes in the temperature response threshold of TRPA1, but enhance its thermal sensitivity and heat-induced openness (Figure 3).

This helps the hot spring snake to respond more quickly to warmer environments
.
The above results are consistent
with the results of thermotaxis experiments.

Figure 3.
TRPA1 hot spring snake unique mutation and structure prediction and patch-clamp experimental results

TRPA1 is also one of
the important molecular components with lip socket/cheek fossa snake sensing infrared heat source.
Infrared snakes perceive infrared mainly due to the unique mutation of TRPA1, which is achieved by changing its temperature-sensitive threshold, which is different from changing TRPA1's sensitivity to heat in hot spring snakes, suggesting that snakes may have two different temperature-sensing molecular strategies (Figure 4).

。 Among them, the ANKs domain in TRPA1 protein is located on the side of the cell membrane, which provides the basis for interaction with ligands and may participate in the adjustment of temperature-sensitive thresholds in the infrared sensing function of snakes.
The TM1 to TM6 domains are located in the transmembrane region and are the main structure of the ion channel, and the mutation of the site in the TM6 region of the hot spring snake may increase the degree of openness under the same temperature stimulation by changing the conformation of the ion channel
.
The research was recently published in The Innovation
, titled "Temperature acclimation in hot-spring snakes and the convergence of cold response.
"

Figure 4.
Differences between TPRA1 and infrared imaging snake TRPA1 mutation sites

The origin and evolution of the hot spring snake is closely related
to the formation and uplift of the Qinghai-Tibet Plateau.
The research team also carried out population genomics research on Tibetan hot spring snakes, exploring the genetic structure of the species, population history dynamics, and the geographical, climatic and microenvironment driving factors
that affect population differentiation.

Based on genome-wide SNPs analysis, Tibetan hot spring snakes are genetically divided into three groups, which are defined as western, central and eastern taxa according to geographical distribution, among which the western taxa is the most genetically different from the other two.
Despite differentiation, gene flow
is widespread between populations.
Among them, the central taxa carries the role of gene exchange and transmission between the eastern and western taxa to a certain extent due to its geographical location.
A study of the population history dynamics of Tibetan hot spring snakes suggests that climatic factors, geographical structure and differences in hot spring microenvironment play an important role in promoting their differentiation and shaping their distribution pattern (Fig.
5).

Figure 5.
Simulation of the level of genetic diversity and population history dynamics of the hot spring snake population

At the same time, as a national key protected species, the research team analyzed
the genetic diversity of Tibetan hot spring snakes.
The results showed that Tibetan hot spring snakes had low genomic heterozygosity (0.
016% to 0.
034%), high inbreeding coefficient (0.
779 to 0.
926) and genetic load, and the analysis of chromosomal structural variation of Tibetan hot spring snakes also reflected the low diversity level
of this species.
The research results can provide scientific support
for the formulation of conservation strategies for Tibetan hot spring snakes and other plateau species.
The results were recently published in Molecular Ecology with the title "Genomic evidence reveals intraspecific divergence of the hot-spring snake (Thermophis baileyi), an endangered reptile endemic to the Qinghai-Tibet Plateau"
。

As one of the highest distribution snake groups in the world, hot spring snakes are highly dependent on the hot spring habitat of the Qinghai-Tibet Plateau, which provides an ideal model
for exploring the extreme environmental adaptation of snakes.
Using the hot spring snake as an animal model, Li Jiatang's research team has long been committed to the study of the
adaptive evolution mechanism of plateau ectothermic animals.
In the future, it is expected to integrate multidisciplinary technical means and multi-dimensional data to continue to deeply explore the "secrets"
of the survival and evolution of such amazing animals on the Qinghai-Tibet Plateau.

Related article links:

1.
Li J-T^#*, Gao Y-D^#, Xie L^# , Deng C, Shi P, Guan M-L, et al.
Comparative genomic investigation of high-elevation adaptation in ectothermic snakes.
PNAS.
2018, 115(33):8406-8411.
doi.
org/10.
1073/pnas.
1805348115.

2.
Yan C^#, Wu W^#, Dong W^#, Zhu B, Chang J, Lv Y, et Li J-T^* .
Temperature acclimation in hot-spring snakes and the convergence of cold response.
The Innovation.
2022, 3(5):100295.
doi: doi.
org/10.
1016/j.
xinn.
2022.
100295.

3.
Yan C, Song M-H, Jiang D, Ren JL, Lv Y, Chang J, et Li J-T^* .
Genomic evidence reveals intraspecific divergence of the hot-spring snake (Thermophis baileyi), an endangered reptile endemic to the Qinghai-Tibet Plateau.
Molecular Ecology 2022, Epub 2022/09/09.
doi: 10.
1111/mec.
16687.
 

4.
Ren J-L, Yan C, Peng Z-L, Li J-T^*.
Sichuan hot-spring snakes imperiled: reason, situation, and protection.
Zoological Research.
2022, 43(1):95.
doi: 10.
24272/j.
issn.
2095-8137.
2021.
321.