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Recent emphasis on learning biology through scientific investigations has focused instruction on understanding and using scientific evidence. To unpack the complexities of evidentiary reasoning, here we present a novel laboratory investigation for teaching the Hardy Weinberg Equilibrium (HWE) in an introductory biology laboratory course that was informed by the Conceptual Analysis of Disciplinary Evidence (CADE) framework. This HWE laboratory investigation highlights evidentiary reasoning with scaffolding questions to target reasoning with and about scientific evidence and it provides students with detailed disciplinary knowledge underpinning their investigation and evidentiary reasoning. To indicate how CADE influenced instruction on evidentiary reasoning during the investigation, changes in one instructor's laboratory discussion questions before and after implementing CADE are provided. Also, our CADE-informed HWE laboratory investigation is compared to other published activities for engaging students with HWE. Findings show that with CADE, the instructor implemented more scaffolds for directing students to consider multiple aspects of evidentiary reasoning and encouraged students' epistemic considerations about the nature, scope and quality of scientific evidence. These changes suggest that CADE can be a practical pedagogical tool to inform improvements in HWE laboratory investigations and to help instructors develop and implement scaffolds to guide students' evidentiary reasoning during a scientific investigation. [ABSTRACT FROM AUTHOR]