Mosquitoes use multiple cues to detect humans, including carbon dioxide, body odor, heat, moisture, and visual cues. Genetic tools like CRISPR-Cas9 have helped researchers study the molecular receptors involved, such as odorant receptors (ORs), ionotropic receptors (IRs), and gustatory receptors (GRs). While any single cue is not fully attractive on its own, mosquitoes integrate cues through multimodal processing, such as CO2 enhancing responses to other cues. Mutating genes like those encoding the CO2 receptor Gr3 or the olfactory receptor co-receptor ORCO impacts but does not eliminate host-seeking behaviors.

1. Genetic analysis of Mosquito
detection of Humans
N.MUGUNDHAN
PALB8139

2. What is the world’s deadliest animal?

3. Yellow fever
Dengue Chikungunya
Zika Malaria
Elephantiasis
Japanese
Encephalitis
West Nile Virus

4. Alexander the Great, conqueror of many nations, was
vanquished by the bite of a tiny mosquito bearing Malarial
parasites.
INTERESTING FACT

5. INTRODUCTION
 Few animals on Earth evoke the antipathy that mosquitoes do.
 They have an ability to sense us, taking flight and
disappearing milliseconds before a fatal bite.
 There are about 3000 species of mosquito, of which about 100
are vectors of human diseases.
 Only female mosquitoes feed on animals &
humans.

6. How Mosquitoes detect Humans ?
Exhaled
Co2
Body odour
Blood type
Secretor
status
Tastants
Vision
Moisture
Body heat

7. Exhaled carbon dioxide / Octenol
 When people and animals breathe, they exhale mixture of
carbon dioxide and Octenol, which is actually a type
of alcohol.
 Exposing female mosquitoes to carbon dioxide (CO2)
induces flight takeoff and sustained flight.
 CO2 is detected by gustatory receptors that are expressed
in the capitate peg sensilla of the
maxillary palps.

8. Body Odor
 Odor is a critical cue that signals the presence of a host
 Body odor is caused by bacterial colonies on the skin.
 Among these compounds are
 Lactic acid
 Ammonia
 Ketones
 Sulfides
 1-octen-3-ol
 Carboxylic acids.

9.  Generally , the stronger a human smells the more they
stand to attract mosquitoes
 The odors are sensed via olfactory receptors, which can
be found on the,
 Mosquito antennae,
 Maxillary palps
 Proboscis.

10. Blood type
A study that was published in Nature (Wood and Dore,1972)
More Attracted Less Attracted

11. Secretor :
Secretes their blood type antigens into body fluids and
secretions like the saliva in your mouth, the mucus
in your digestive tract and respiratory cavities, etc. ...
Non-secretor :
Have little to none of their blood
type antigens into these same fluids.
Secretor status

12.  Heat attracts mosquitoes to their hosts at close range.
 Electrophysiological studies revealed that there is an
antagonistic pair of thermosensitive neurons.
 Coeloconic sensilla of the Ae. aegypti antennal tip where
one sensillum is tuned to temperature rise and the other
is sensitive to cold.
 Mosquitoes will land on inanimate
objects set at human body temperature
in the presence of CO2.
Body heat

13.  Mosquitoes are guided by visual cues to fly towards their hosts.
 Compound eyes that are sensitive to varying light intensity.
 Play an intermediate role in host detection by integrating long-
range odor plume tracking with shorter-range cues.
 For instance, CO2 or human odor can increase the ability of
mosquitoes to pay attention to visual cues by enhancing
visual flight navigation to the host.
Visual Cues

14.  The tastants on the skin also likely to promote blood feeding
once they land.
 After landing, they soon pierce the skin and draw blood from
small blood vessels.
 The mouthparts of the female mosquito are highly specialized
for blood feeding and contain sensory hair cells which help
locate blood under the skin.
Tastants

15.  It is no secret that mosquitoes are attracted to moist
locations.
 They breed and lay eggs in shallow pools of water.
 Moisture on a person’s skin and
the vapor in their breath is a
prime invitation for mosquitoes.
Moisture

16. Insects have evolved complex repertoires of receptors to
respond to chemical stimuli in their environment including:
 Odorant receptors (ORs)
 Ionotropic receptors (IRs)
 Gustatory receptors (GRs)
Molecular sensors of human cues

17.  The ORs are expressed in the dendrites of ORNs.
 The OR pathway plays a critical role in mosquito preference for
human hosts and DEET repellency.
 These Ors tested seemed to be narrowly tuned to several odor
components that emanate from humans such as,
 1-octen-3-ol (present in human breath)
 2,3-butanedione (by-product of
metabolized sweat)
 Indole (human sweat volatile).
Odorant receptors (ORs)

18.  The IRs are expressed in the dendrites of the ORNs
innervating the coeloconic sensilla .
 There are at least two IR co-receptors, Ir8a and Ir25a.
 These co-receptors form an odor-responsive ion channel with
odor-selective.
 IRs respond primarily to
 Amines and Acids
 Moisture
 Temperature sensing
 Possibly in the auditory system
Ionotropic receptors (IRs)

19. Although GRs are usually involved in taste, specialized GRs
have been implicated in other sensory modalities in insects
including,
 Light sensing
 Warmth sensing
 CO2 detection
Gustatory receptors (GRs)

20. Our ability to understand the molecular basis of
mosquito behavior has been enhanced by the recent
development of genome editing tools such as
 CRISPR-Cas9 RNA guided nucleases
 TALE-effector Nucleases (TALENS)
 Zinc Finger Nucleases (ZFNs) in Anopheles
and Aedes
Genetic Analysis

21.  Cas9 (CRISPR associated protein 9) is an RNA-
guided DNA endonuclease enzyme associated with
the CRISPR (Clustered Regularly Interspaced Short
Palindromic Repeats) adaptive immunity system
CRISPR-Cas9

22.  Transcription activator-like effecto nucleases (TALEN)
are restriction enzymes that can be engineered to cut specific
sequences of DNA
TALEN

23.  Zinc-finger nucleases (ZFNs) are artificial restriction
enzymes can be engineered to target specific
desired DNA sequences.
 By taking advantage of endogenous DNA repair
machinery,can be used to precisely alter the genomes.
ZFNs

24.  These approaches facilitate targeted mutagenesis at
any gene of interest to determine their contribution to
host detection and blood feeding.
 To integrate genetic tools into the mosquito genome to
map the neural circuits that enable these behaviors.
 Targeted mutagenesis of olfactory receptors have already
been successfully performed in Ae. aegypti.

25.  Genetic analysis has demonstrated that mosquitoes
integrate multiple stimuli to find their hosts.
 One of the most striking examples is the gating of multiple
cues by CO2.
 In Ae. aegypti mosquito attraction
requires at least two cues.
Multimodal integration of human cues

26.  For example, neither thermal
cues, nor lactic acid are
attractive on their own.
 If CO2 is combined with
either of these cues, mosquito
attraction is greatly enhanced.
 If sensitivity to CO2 is lost,
as in Gr3 mutants, this
synergistic effect of CO2 does
not occur.

27. Gr3 MUTANTS
 To determine the relative contribution of carbon dioxide
(CO2) detection to mosquito host-seeking behavior.
 We mutated the AaegGr3 gene, a subunit of the heteromeric
CO2 receptor in Aedes aegypti mosquitoes.
 Gr3 mutants lack electrophysiological and behavioral
responses to CO2.

28. ORCO MUTANTS
 Host odor may also gate mosquito responses to hosts.
 Mutant mosquitoes lacking the olfactory receptor co-
receptor (orco) gene.
 Behaviourally, ORCO mutant mosquitoes have severely
reduced attraction to human scent in the absence of CO2.
 But in the presence of CO2, there was no difference
between the wild-type and orco mutant mosquitoes.

29.  Olfactory receptor neurons (ORN) from the labella on the
proboscis to the suboesophageal zone (SEZ) of the brain
integrate odor and taste cues during blood feeding.
(Riabinina et al., )
 In Ae. aegypti, in vivo calcium imaging revealed the activation of
some ORs by volatile compounds in
the blood, and removing the function
of the ORs in the stylet impairs blood
feeding.
Odour and Taste

30.  We have seen about the multiple cues that attract
mosquitoes to humans and their molecular sensors.
 Host-seeking is not completely abolished even when either
the CO2-sensing or OR pathways were disrupted in
Ae.aegypti.
 The ability to integrate host sensory cues represents an
essential mechanism employed by mosquitoes to guide
host detection and blood-feeding behavior.
Summary

31. Genetic analysis of mosquito detection of humans.
Joshua I Raji and Matthew DeGennaro
-ScienceDirect
REFERENCE