Corticotropin-Releasing Hormone (CRH) Gene Family Duplications in Lampreys Correlate With Two Early Vertebrate Genome Doublings

Dan Larhammar,João C R Cardoso,Christina A Bergqvist

doi:10.3389/fnins.2020.00672

Abstract

The ancestor of gnathostomes (jawed vertebrates) is generally considered to have undergone two rounds of whole genome duplication (WGD). The timing of these WGD events relative to the divergence of the closest relatives of the gnathostomes, the cyclostomes, has remained contentious. Lampreys and hagfishes are extant cyclostomes whose gene families can shed light on the relationship between the WGDs and the cyclostome-gnathostome divergence. Previously, we have characterized in detail the evolution of the gnathostome corticotropin-releasing hormone (CRH) family and found that its five members arose from two ancestral genes that existed before the WGDs. The two WGDs resulted, after secondary losses, in one triplet consisting of CRH1, CRH2, and UCN1, and one pair consisting of UCN2 and UCN3. All five genes exist in representatives for cartilaginous fishes, ray-finned fishes, and lobe-finned fishes. Differential losses have occurred in some lineages. We present here analyses of CRH-family members in lamprey and hagfish by comparing sequences and gene synteny with gnathostomes. We found five CRH-family genes in each of two lamprey species (Petromyzon marinus and Lethenteron camtschaticum) and two genes in a hagfish (Eptatretus burgeri). Synteny analyses show that all five lamprey CRH-family genes have similar chromosomal neighbors as the gnathostome genes. The most parsimonious explanation is that the lamprey CRH-family genes are orthologs of the five gnathostome genes and thus arose in the same chromosome duplications. This suggests that lampreys and gnathostomes share the same two WGD events and that these took place before the lamprey-gnathostome divergence.

Highlights

The corticotropin-releasing hormone (CRH) family consists in vertebrates of five structurally related neuropeptides that are involved in the regulation of physiological response to stress, emotional behavior, and anxiety (Vale et al, 1981; Dunn and Berridge, 1990; Koob and Heinrichs, 1999; Lovejoy and Balment, 1999; Gysling et al, 2004; Fox and Lowry, 2013)
Blast searches with the known CRH-family members identified five CRH-family sequences in both the sea lamprey and the Arctic lamprey genomes
Analysis of the sea lamprey germline genome assembly revealed that the five CRH-family genes map to five different genome regions: scaffold_00040 (GL480439 in ENSEMBL), scaffold_82 (GL476347 in ENSEMBL), scaffold_00003, scaffold_00017, and scaffold_00057

Summary

Introduction

The corticotropin-releasing hormone (CRH) family consists in vertebrates of five structurally related neuropeptides that are involved in the regulation of physiological response to stress, emotional behavior, and anxiety (Vale et al, 1981; Dunn and Berridge, 1990; Koob and Heinrichs, 1999; Lovejoy and Balment, 1999; Gysling et al, 2004; Fox and Lowry, 2013). Two additional urocortins were discovered in silico in mammals and named UCN2 (Reyes et al, 2001) and UCN3 (Lewis et al, 2001), both of which are 38 amino acids long in mammals They were soon found in other classes of vertebrates, including ray-finned fishes. CRH2 is the most recently discovered member and was initially identified in cartilaginous fish and was suggested to be specific to these species (Nock et al, 2011), but subsequent reports demonstrated its presence in other vertebrate classes with the exception of placental mammals and teleosts (Grone and Maruska, 2015a; Cardoso et al, 2016)

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