I investigated the extent of variation of venom protein composition (venome) and neurotoxicity in the Northern Pacific (Crotalus oreganus oreganus) and Southern Pacific (C. o. helleri) rattlesnakes, with special emphasis on geographic variation across the species’ California range. In the first of three empirical studies, I used reversed-phase liquid chromatography and mass spectrometry to examine the venome of four C. o. helleri populations. Substantial geographic variation existed, with small basic peptides (myotoxic β-defensins) expressed in large amounts by all populations, metalloproteinases abundant in two populations but only moderate and trace amounts in the other two populations, and a potent presynaptic neurotoxic phospholipase A2 present in just one population. The second study comprised a more thorough analysis of venome variation and neurotoxicity among C. oreganus individuals at 40 sampling locations across their California range. In this study, I tested for associations between venom composition and three potential factors that contribute to venome variation: geographic distance, genetic relatedness, and environmental variation. Again, venom profiles and neurotoxicity varied substantially across the species’ California distribution. Environmental variables had the strongest and most consistent association with venom composition among statistical models, but geographic distance and genetic distance were also significant in several models. The third study examined diet and ontogeny as possible sources of venom variation in two populations of C. o. helleri having highly divergent venoms. For this study, I analyzed the gut contents and venomes of juvenile and adult snakes from a coastal population, Santa Catalina Island, and a high-elevation montane population, Mt. San Jacinto. I found no significant difference in diet composition (lizard versus mice) between the two populations. Differences in venom profiles between snake age classes were limited to three protein families in the Mt. San Jacinto populations and one in the Santa Catalina Island population, but effect sizes for overall ontogenetic change in venom was similar for the two populations. Collectively, these findings document the considerable extent of variation in venom composition and toxicity among populations within the species and support the emerging consensus that such variation is driven by a combination of environmental, geographic, and phlyogenetic factors.

LLU Discipline



Basic Sciences


School of Medicine

First Advisor

Hayes, William K.

Second Advisor

Brand, Leonard R.

Third Advisor

Dunbar, Stephen G.

Fourth Advisor

Filippov, Valeri

Fifth Advisor

Nisani, Zia

Sixth Advisor

Standish, Timothy

Degree Name

Doctor of Philosophy (PhD)

Degree Level


Year Degree Awarded


Date (Title Page)




Library of Congress/MESH Subject Headings

Crotalus; Northern Pacific Rattlesnake; Southern Pacific Rattlesnake; Rattlesnakes - Venom; Ontogeny; Snake Venoms; Crotalid Venoms;

Subject - Local

Venom Protein Composition; Neurotoxicity; Reversed-phase Liquid Chromatography; Mass Spectrometry; Presynaptic Neurotoxic Phospholipase



Page Count


Digital Format


Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.


Loma Linda University Electronic Theses and Dissertations

Collection Website



Loma Linda University. Del E. Webb Memorial Library. University Archives

Included in

Biology Commons