A phylogeographic investigation of African monkeypox

Abstract

Monkeypox is a zoonotic disease caused by a virus member of the genus Orthopoxvirus and is endemic to Central and Western African countries. Previous work has identified two geographically disjuct clades of monkeypox virus based on the analysis of a few genomes coupled with epidemiological and clinical analyses; however, environmental and geographic causes of this differentiation have not been explored. Here, we expand previous phylogenetic studies by analyzing a larger set of monkeypox virus genomes originating throughout Sub-Saharan Africa to identify possible biogeographic barriers associated with genetic differentiation; and projected ecological niche models onto environmental conditions at three periods in the past to explore the potential role of climate oscillations in the evolution of the two primary clades. Analyses supported the separation of the Congo Basin and West Africa clades; the Congo Basin clade shows much shorter branches, which likely indicate a more recent diversification of isolates within this clade. The area between the Sanaga and Cross Rivers divides the two clades and the Dahomey Gap seems to have also served as a barrier within the West African clade. Contraction of areas with suitable environments for monkeypox virus during the Last Glacial Maximum, suggests that the Congo Basin clade of monkeypox virus experienced a severe bottleneck and has since expanded its geographic range.

Figure 1

Isolates included in the phylogenetic analysis (black circles). Isolates from Kugelman et al. [31] are mapped to the centroid of the Health Zone where they were reported. Isolates from Copenhagen, Walter Reed, Paris, and Rotterdam are not mapped because their African origin is unknown. Isolate from Sudan is shown at the outbreak locality, but is thought to have been imported from Northern DRC.

Figure 2

(A) Majority-rules consensus tree. Clade credibility values for all nodes are 0.99–1.0, except from one polytomy indicated in the text (¤). Branch lengths are shown to scale. CB = Congo Basin Monkeypox clade; WA = West African Monkeypox clade. Groups are indicated by the roman number in parenthesis; (B) Map showing major geographic features of the area and the distribution of isolates used in the phylogenetic analysis, colors indicate groups: I = black, II = blue, III = red, IV = orange, V = green, and WA = purple. Isolates from Copenhagen, Walter Reed, Paris and Rotterdam are mapped to a point in the sea indicated with an asterisk (*) because their African origin is unknown.

Figure 3

Model agreement maps from GARP (left column) and Maxent (right column) based on the 25 locality subsets; darker shade = higher agreement. Models projected onto present day environmental conditions (A,B), Mid-Holocene (MidHol: C,D), Last Glacial Maximum (LGM: E,F), and the Last Interglacial period (LIG: G and H). White circles represent MPX localities used for model development.