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Studies reveal secrets of malaria transmission

Anopheles albimanus mosquito

Credit: James Gathany

Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.

There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.

Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.

Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.

The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.

In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.

A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.

Both groups described their work in Science Express.

The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.

Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.

“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.

The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.

“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”

The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.

The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.

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Anopheles albimanus mosquito

Credit: James Gathany

Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.

There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.

Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.

Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.

The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.

In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.

A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.

Both groups described their work in Science Express.

The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.

Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.

“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.

The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.

“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”

The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.

The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.

Anopheles albimanus mosquito

Credit: James Gathany

Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.

There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.

Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.

Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.

The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.

In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.

A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.

Both groups described their work in Science Express.

The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.

Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.

“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.

The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.

“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”

The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.

The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.

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