Extensive recombination-induced disruption of genetic interactions is highly deleterious but can be partially reversed by small numbers of secondary recombination events.
Although homologous recombination can potentially provide viruses with vastly more evolutionary options than are available through mutation alone, there are considerable limits on the adaptive potential of this important evolutionary process. Primary among these is the disruption of favorable coevolved genetic interactions that can occur following the transfer of foreign genetic material into a genome. Although the fitness costs of such disruptions can be severe, in some cases they can be rapidly recouped by either compensatory mutations or secondary recombination events. Here, we used a maize streak virus (MSV) experimental model to explore both the extremes of recombination-induced genetic disruption and the capacity of secondary recombination to adaptively reverse almost lethal recombination events. Starting with two naturally occurring parental viruses, we synthesized two of the most extreme conceivable MSV chimeras, each effectively carrying 182 recombination breakpoints and containing thorough reciprocal mixtures of parental polymorphisms. Although both chimeras were severely defective and apparently noninfectious, neither had individual movement-, encapsidation-, or replication-associated genome regions that were on their own "lethally recombinant." Surprisingly, mixed inoculations of the chimeras yielded symptomatic infections with viruses with secondary recombination events. These recombinants had only 2 to 6 breakpoints, had predominantly inherited the least defective of the chimeric parental genome fragments, and were obviously far more fit than their synthetic parents. It is clearly evident, therefore, that even when recombinationally disrupted virus genomes have extremely low fitness and there are no easily accessible routes to full recovery, small numbers of secondary recombination events can still yield tremendous fitness gains. Importance: Recombination between viruses can generate strains with enhanced pathological properties but also runs the risk of producing hybrid genomes with decreased fitness due to the disruption of favorable genetic interactions. Using two synthetic maize streak virus genome chimeras containing alternating genome segments derived from two natural viral strains, we examined both the fitness costs of extreme degrees of recombination (both chimeras had 182 recombination breakpoints) and the capacity of secondary recombination events to recoup these costs. After the severely defective chimeras were introduced together into a suitable host, viruses with between 1 and 3 secondary recombination events arose, which had greatly increased replication and infective capacities. This indicates that even in extreme cases where recombination-induced genetic disruptions are almost lethal, and 91 consecutive secondary recombination events would be required to reconstitute either one of the parental viruses, moderate degrees of fitness recovery can be achieved through relatively small numbers of secondary recombination events.
Molecular and Cell Biology Department, University of Cape Town, Cape Town, South Africa Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Adérito L
AL
Monjane
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa darrenpatrickmartin@gmail.com.
Darren P
DP
Martin
Molecular and Cell Biology Department, University of Cape Town, Cape Town, South Africa.
Francisco
F
Lakay
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Brejnev M
BM
Muhire
Department of Botany and Horticulture, Maseno University, Maseno, Kenya.
Daniel
D
Pande
School of Biological Sciences and Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand Department of Plant Pathology and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA Electron Microscope Unit, Division of Medical Biochemistry, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
Arvind
A
Varsani
South African National Bioinformatics Institute, MRC Unit for Bioinformatics Capacity Development, University of the Western Cape, Bellville, South Africa.
Gordon
G
Harkins
Molecular and Cell Biology Department, University of Cape Town, Cape Town, South Africa.
Dionne N
DN
Shepherd
Molecular and Cell Biology Department, University of Cape Town, Cape Town, South Africa Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Edward P
EP
Rybicki
D000220:Adaptation, Biological; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D059765:Homologous Recombination; D026762:Maize streak virus / Q000235:genetics* / Q000502:physiology; D050296:Microbial Viability; D010935:Plant Diseases / Q000821:virology; D017422:Sequence Analysis, DNA; D003313:Zea mays / Q000821:virology
D004279:DNA, Viral