Camels have earned the nickname ‘ships of the desert’ due to their ability to glide across this hot and arid environment where there is very little water. Research has focused intensively on some of the adaptations that have helped them to survive these conditions, but most of this research has focused on characteristics such as fat distribution and urine production. Dr Yu Cao from Tianjin University of Traditional Chinese Medicine, has gone beneath the surface to understand how animal resistance to stress is controlled at the molecular level, identifying novel pathways that are involved in resistance to stress in camels.
Camels have long been known for their ability to withstand high temperatures and periods of drought. How these desert-dwelling animals adapt to these conditions has been intensively studied, with research demonstrating that, to survive these harsh conditions, camels are able to reduce their body fat distribution while building a fat store in their humps which minimises their insulation. They are also able to reduce their water loss by producing highly concentrated urine and dry faeces. While all of these adaptations have been shown to help camels survive life in the desert, little work has looked at what is happening in their cells at the molecular level. Recent work by Dr Yu Cao from Tianjin University of Traditional Chinese Medicine has aimed to shed light on what is happening at the post-transcriptional level under water deprivation and salt stress, using omics technology to study different types of RNA, with a focus largely on non-coding RNA.
RNA, or ribonucleic acid, is a class of molecules with single-stranded, double-stranded or circular structures, involved in protein synthesis. Previously it was thought that non-coding RNA was ‘junk RNA’ and had no major function, as it did not code for proteins being made within the cell. More recently it has been shown that non-coding RNAs, which include long non-coding RNA and micro RNA, are involved in controlling the processes of transcription and translation which enable us to build proteins in our bodies from the information encoded in our DNA. Here we look at some of the work Cao has carried out to study the role non-coding RNAs play in animal resistance to stress, with the aim of applying this information to strategies of molecular breeding of camels and other mammals found in dry and arid areas.
Non-coding RNAs and kidney stress
In order to live successfully in the desert, camels have had to adapt to living in conditions of extreme heat where there is very little water available. As a result, they have developed several characteristics that make them resistant to stress caused by high salt levels and low water availability. In recent work, Cao sought to understand the role of non-coding RNA in the regulation of animal resistance to these two stresses. Non-coding RNA is important because, unlike coding RNA, it is generally not translated into protein and is instead involved in the regulation of gene expression.
While working in the Inner Mongolia Key Laboratory of Bio-manufacture, Cao and his collaborators examined gene expression in the renal cortext – the outer part of the kidney – in the Alxa Bactrian Camel (Camelus bactrianus) using RNA-sequencing technology. They found that the expression of several non-coding RNAs was affected by salt- and/or water-deprivation stress. More importantly, the researchers identified four novel non-coding RNAs that were involved in salt resistance in the renal cortex, and proposed a potential pathway regulated by non-coding RNAs that could explain how a camel’s renal cortex responds to stress caused by salt and water deprivation. This important information could be used to provide a basis for the development of a therapy that would treat a disease similar to high blood pressure in humans.
Diving inside the kidney
In further work, Cao explored resistant-related molecular regulation in the innermost part of the kidney – the renal medulla – in response to water-deprivation stress in camels. Cao used RNA sequencing and reverse transcription qualitative polymerase chain reaction (qRT-PCR) techniques to examine mRNA and two types of non-coding RNA: long non-coding RNA and micro RNA. He found significant changes in three water-deprivation resistant protein-coding genes that were involved in weakened cell dehydration, aerobic respiration and metabolism, as well as enhanced anti-oxidative capability.
More specifically, the changes in expression of these genes suggest that, under water deprivation, camels suppress cell dehydration and inhibit aerobic respiration and metabolism by decreasing the generation of NADH and FADH2, naturally occurring coenzymes which are involved in the production of energy via the citrate cycle. In addition, the down-regulation of certain genes also reduces the amount of oxygen transported to the mitochondria, which further decreases respiration and metabolism. This is not surprising, as a reduction in metabolism and respiration are common methods used by animals that inhabit dry and arid regions. The data from this study demonstrates how camels positively respond to water-deprivation stress at the molecular level by exploring the role of non-coding RNAs, which provides valuable information on how animals can adapt to arid surroundings. This work provides inspiration for future work to assess how breeding can help animals adapt to hot environments that receive very little water.
Altering gene function
While the kidneys have been the main focus of research into resistance to water deprivation, the small intestine and the liver have also been shown to play active roles in salt and water metabolism. In another study, Cao examined how salt and water-deprivation stress impacted resistance genes found in the small intestine and the liver. More specifically, the group examined alternative splicing events that occurred under stressful conditions. Alternative splicing is a process that results in different protein variants being synthesised that may have different cellular functions or properties and therefore be involved in different processes depending on what the cell needs.
Cao and his collaborators used high-throughput sequencing to find several genes that contributed to cellular stress resistance. These genes had roles in a number of processes including reducing water loss, inhibiting excessive movement of sodium into the cell, improving protective barriers, sodium ion regulation, and maintaining uridine content. The results showed that the occurrence of alternative splicing in the genes studied was dependant on the stress experienced and the organ studied. In the ileum, the genes studied were more likely to undergo alternative splicing that resulted in similar molecular functions under water-deprivation stress, whereas under salt stress they were more likely to undergo alternative splicing that resulted in more diverse functions. The opposite was observed in the liver. Cao hopes this work can provide new insights for human diseases caused by high salt intake.
Cao’s work demonstrates novel pathways that are involved in the ability of camels to tolerate salt- and water-deprivation stress. His work shows that the response to these stressors is mediated by non-coding RNAs and alternative splicing events and that these differ depending on the organ that is examined. This work provides novel insights into how camels have adapted to stress, which have some implications for establishing new animal models and treating human diseases caused by high salt intake. Moving forward, Cao would like to use these results to help establish a novel breeding pattern which is known as ‘polarity breeding’. This would use information from herbal pharmacology to provide nutritional supplements that have been shown to contribute to the natural induction of resistance to stress. More specifically, evidence suggests that certain plants, such as alfalfa, have high nutritional and medical values and are used to treat domestic animals by herdsmen; polarity breeding would look to harness this evidence in its attempt to contribute to bio-resistance.
- Zhang, D, Pan, J, Cao, J, Cao, Y, Zhou, H, (2020). Screening of drought-resistance related genes and analysis of promising regulatory pathway in camel renal medulla. Genomics, 112(3), 2633-2639. doi.org/10.1016/j.ygeno.2020.02.014
- Zhang, D, Pan, J, Zhou, H, Cao, Y, (2020). Evidence from ileum and liver transcriptomes of resistance to high-salt and water-deprivation conditions in camel. Zoological Letters, 6, 8. doi.org/10.1186/s40851-020-00159-3
- Cao, Y, Zhang, D, Zhou, H, (2019). Key genes differential expressions and pathway involved in salt and water-deprivation stresses for renal cortex in camel. BMC Molecular Biology, 20(1), 11. doi.org/10.1186/s12867-019-0129-8
Dr Yu Cao researches how animal resistance to stress is controlled at the molecular level.
Support for the investigations showed in this article was from the National Natural Science Foundation of China.
Dr Cao thanks Associate Professor Dong Zhang, Professor Yanru Zhang and Professor Huanmin Zhou from the Inner Mongolia Key Laboratory of Bio-manufacture in Inner Mongolia Agricultural University for their support. Dr Cao is very grateful to Professor Boli Zhang who led him to enter the herbal field.
Yu Cao was born in Tianjin, China. He obtained his Bachelor of Science degree in agriculture at Huazhong Agricultural University, then he received his Doctor of Science degree at Inner Mongolia Agricultural University in China. Dr Cao is currently a post-doctoral research associate at Tianjin University of Traditional Chinese Medicine.