Identification Of Mammalian Ultra-conserved Elements And Application In Livestock Breeding

Due to the relaxation of natural selection,during the rapid breeding of livestock,some individuals have de novo mutations,thereby introducing potential genetic diseases and defects into the livestock population.Therefore,it is particularly important to identify the key conserved regions in the livestock genome,and to understand the rules of site mutations in these regions,as well as predict whether they will affect the biological functions of livestock.Evolution conservation is a powerful signature to functional elements in the genome and keeping them unchanged may help to exercise the basic life activities and adaptive functions of the species,especially the class of ultra-conserved elements(UCEs).However,some UCEs rapidly evolved in specific lineages and whether they contribute to adaptive evolution are still controversial.It is also unclear whether the mutation sites in these important areas affect livestock selection.Here,using 95 published mammalian genomes were downloaded from NCBI to acquire UCEs by reconstructing mammalian ancestral sequences.The UCEs and their variation in goat population were analyzed.And the following results were obtained:1.According to the phylogenetic tree we constructed,placental mammals were divided into 8 branches: Cetartiodactyla,Chiroptera,Insectivora,Perissodactyla,Carnivora,Glires,Primates,Afrotheria.Finally,the ancestral sequence longer than 200 bp,which was 100% identical with at least one branch and with at least 80% identity across all branches,was defined as UCEs of this taxon.In total,2,191 mammalian UCEs were identified.More than half(1,196)of the mammalian UCEs were 100% identical with ancestral sequences in at least two branches,and 48 UCEs are absolutely conserved among all branches.We also examined the conservation of these UCEs in all vertebrate taxa.We found that mammalian UCEs are almost(>80%)all present homology sequence in Amniote,about half of UCEs were conserved in Tetrapod,partial initiative conserved in Gnathostomata(? 30%)and nearly inexistence homology in lamprey and hagfish.These evidences indicate that the evolution of UCEs in several vertebrate genomes and found that they were generated and expanded on a large scale during tetrapod,amniote and gnathostomata evolution.In addition,163 UCEs overlap with highly conserved ruminant elements.2.To analyze the genomic distribution of UCEs,the mammalian UCEs were annotated with human gene annotations.Here,we found more UCEs were located in noncoding regions,34.9% mammalian UCEs were located in the intronic region,as well as 25.8% mammalian UCEs were located in the intergenic region.In addition,analysis of published 55 human samples representing 11 tissues implying the adjacent genes of UCEs were more prone to widespread expression and possessed lower expression diversity.And the KEGG pathway analysis of the adjacent genes of mammalian UCEs shows that most enrichment genes play a role in the cancer pathway,neural correlated pathway,spliceosome and circadian rhythm.3.To evaluate the variability of UCEs,we detected the accelerated evolved UCEs in each mammalian orders.The results showed that 0.59%-13.2% UCEs were accelerated evolution in specific orders of mammalian.And Chiroptera possessed the most amount accelerated evolution UCEs(290,13.2%).Besides,our results revealed that even the 48 extremely mammalian UCEs,which exist absolutely identical sequences among 8 mammalian orders,possessed mutations in specific species as well.It is worth noting that 27.3%-62.1% rapidly evolved mammalian UCEs in different branches were driven by gBGC.We also found a gBGC event occur at the ancient mammals,and existence in the evolution of mammals.The results implying this gBGC event maybe contributes to the adaptative evolution of species.What is more,changes in gBGC of UCEs in domestic animals may not affect their basic functions.4.Based on the analysis of SNPs on UCEs in goat populations,it is shown that the distribution rate of SNPs on UCEs is significantly lower and most of them are low-frequency.These mutations with low-frequency occurring in highly conserved regions may pose a potential threat to livestock health.Therefore,they should be avoided as much as possible when breeding livestock.However,we found that the 12 SNPs located on UCEs have a frequency of 0 in the wild population,have a certain frequency distribution in different domestic populations,and are located on the highly conserved elements of ruminants.Three of them are located in the intron region of the SPATA17 gene,which is a gene specifically expressed in the testis and related to spermatogenesis.Therefore,the SPATA17 gene may play a role in the breeding of livestock.These SNPs located on UCEs may be able to provide guidance for the selection of breeding rams.In summary,this study uses a large number of mammalian genomes and transcriptomes data to explore the genomic characteristics of UCEs,as well as the role of gBGC-driven UCEs in accelerating evolution.In addition,it provides new ideas for the selection of livestock.